Unnamed: 0
int64 0
2.34M
| title
stringlengths 5
21.5M
| abst
stringlengths 1
21.5M
|
|---|---|---|
2,338,200 |
Incidence and mutation rates of Huntington's disease in Spain: experience of 9 years of direct genetic testing.
|
Prior to the discovery of the Huntington's disease (HD) mutation, the prevalence, incidence, and new mutation rates for this disease were based on the presence of progressive choreic movements and a positive family history.</AbstractText>To evaluate the uptake of the HD genetic analysis in Spain, and to provide additional information on the epidemiology of this disease from the experience of 9 years of direct genetic testing.</AbstractText>From 1994 to 2002, CAG repeat length was determined in 317 patients with symptoms compatible with HD. In all cases, demographic, clinical, and family data were carefully reviewed.</AbstractText>HD diagnosis (CAG repeat length >/=36) was confirmed in 166 (52%) symptomatic cases. Of these, 76 (45.8%) reported a positive family history and in 21 cases (12.7%) family history was negative. New mutation events were genetically proven in three families and highly suspected in another, estimating that the minimum new mutation rate for HD in our population is >4%, with a potential mutation rate of 8%. More than 16% of all HD cases had late onset (>59 years) of symptoms, and in three quarters of these the family history was negative. The incidence rate for the autonomous communities of Navarra and the Basque country, based on the number of newly diagnosed cases by genetic testing, was 4.7 per million per year.</AbstractText>Direct HD genetic testing shows that the incidence and mutation rates of the disease are 2-3 times higher than previously reported. We also demonstrated the relevance of CAG repeat length assessment in diagnosing patients with late onset of symptoms and negative family history for HD.</AbstractText>
|
2,338,201 |
A chimeric N-terminal Escherichia coli--C-terminal Rhodobacter sphaeroides FliG rotor protein supports bidirectional E. coli flagellar rotation and chemotaxis.
|
Flagellate bacteria such as Escherichia coli and Salmonella enterica serovar Typhimurium typically express 5 to 12 flagellar filaments over their cell surface that rotate in clockwise (CW) and counterclockwise directions. These bacteria modulate their swimming direction towards favorable environments by biasing the direction of flagellar rotation in response to various stimuli. In contrast, Rhodobacter sphaeroides expresses a single subpolar flagellum that rotates only CW and responds tactically by a series of biased stops and starts. Rotor protein FliG transiently links the MotAB stators to the rotor, to power rotation and also has an essential function in flagellar export. In this study, we sought to determine whether the FliG protein confers directionality on flagellar motors by testing the functional properties of R. sphaeroides FliG and a chimeric FliG protein, EcRsFliG (N-terminal and central domains of E. coli FliG fused to an R. sphaeroides FliG C terminus), in an E. coli FliG null background. The EcRsFliG chimera supported flagellar synthesis and bidirectional rotation; bacteria swam and tumbled in a manner qualitatively similar to that of the wild type and showed chemotaxis to amino acids. Thus, the FliG C terminus alone does not confer the unidirectional stop-start character of the R. sphaeroides flagellar motor, and its conformation continues to support tactic, switch-protein interactions in a bidirectional motor, despite its evolutionary history in a bacterium with a unidirectional motor.
|
2,338,202 |
Variable selection pressures across lineages in Trichodesmium and related cyanobacteria based on the heterocyst differentiation protein gene hetR.
|
Due to the irreversible inhibition of nitrogenase by O2, N2 fixation is incompatible with the oxygenic photosynthesis of cyanobacteria. These organisms have therefore evolved various strategies for growing diazotrophically. One group of N2-fixing cyanobacteria has specialized cells, heterocysts, which contain the nitrogenase, lack the oxygenic photosystem II, and are virtually anoxic inside as the result of respiratory activity and a thick glycolipid cell wall. The hetR gene encodes a serine protease which is thought to be involved in the regulation of heterocyst development and in DNA binding. Although hetR is also present in many non-heterocystous N2-fixing cyanobacteria, its function in these organisms is unknown. In this study, hetR sequences of the N2-fixing, non-heterocystous cyanobacterium Trichodesmium spp. and related genera were examined for signatures of selection. In parsimony- or distance-based hetR phylogenies, the filamentous non-heterocystous cyanobacteria Symploca sp. and Leptolyngbya sp. were closest to Trichodesmium sp. However, accommodating molecular attributes of hetR such as nucleotide frequencies and rate heterogeneity in phylogenetic analyses suggested that many other genera could not be excluded as sister taxa of Trichodesmium. Maximum likelihood analysis of the dN/dS ratio (omega) showed that-irrespective of the use of Symploca, Leptolyngbya, or more distant taxa as an outgroup-the lineage between an outgroup and Trichodesmium (omega1=0.02-0.05) and a lineage leading to Trichodesmium erythraeum (omega1=0.02) were under much stronger purifying selection than the other lineages in Trichodesmium (omega0=0.13-0.32). Although the results from the maximum likelihood analyses are most trustworthy because of codon usage bias in Trichodesmium, the results from a simpler tree-based McDonald-Kreitman test were in general agreement. Due to their quite different assumptions, the combination of these two methods of analysis circumvents multiple testing which, in general, is problematic when using branch models. Although the causal selective forces underlying the substitution patterns in hetR have not yet been identified, these findings parallel the variety of physiological, molecular, and behavioral differences in cyanobacteria related to N2 fixation. The heterogeneity of selection pressures in Trichodesmium is more surprising, because multiple adaptation mechanisms have not been described in this genus.
|
2,338,203 |
Sex-linked recombination variation and distribution of disease-related genes.
|
Analysis of the distribution of recombination along human chromosomes and correlation with sequence features and genes have been previously performed on one genetic map for a given chromosome, limiting therefore their validity and precision. In this paper, we circumvent these issues: (1) by testing the correlation between recombination frequency in sex-specific versions of three genetic maps of chromosome 21 and their content in disease-related loci compared to the distribution of genes along the chromosome, and (2) by reanalysing the previously reported chromosome 22 results (Chelala et al., J. Biol. Syst. 10 (2002) 303-317) with updated version of the sequence and mapping tools. Recombination hot zones were detected and analysed on each genetic map. Despite local differences, for chromosome 21, recombination hot zones were found relatively enriched in disease-related genes on the male genetic maps. This contrasts with the previously described enrichment of the chromosome 22 female genetic map hot zones in disease-related loci (Chelala et al., J. Biol. Syst. 10 (2002) 303-317), which was confirmed with the updated data and tools. Our study demonstrates that the use of different data sets and tools have only a local impact on the distribution of genetic recombination hot zones and provides evidence for gender-specific differences in enrichment in disease-related loci in relation with recombination frequency. Automation of such analyses and extension to the entire human genome will be required in order assess the general character of these observations and to advance in the understanding of genome-wide recombination patterns to help the process of identifying disease-causing genes.
|
2,338,204 |
Testing alternative mechanisms of evolutionary divergence in an African rain forest passerine bird.
|
Abstract Models of speciation in African rain forests have stressed either the role of isolation or ecological gradients. Here we contrast patterns of morphological and genetic divergence in parapatric and allopatric populations of the Little Greenbul, Andropadus virens, within different and similar habitats. We sampled 263 individuals from 18 sites and four different habitat types in Upper and Lower Guinea. We show that despite relatively high rates of gene flow among populations, A. virens has undergone significant morphological divergence across the savanna-forest ecotone and mountain-forest boundaries. These data support a central component of the divergence-with-gene-flow model of speciation by suggesting that despite large amounts of gene flow, selection is sufficiently intense to cause morphological divergence. Despite evidence of isolation based on neutral genetic markers, we find little evidence of morphological divergence in fitness-related traits between hypothesized refugial areas. Although genetic evidence suggests populations in Upper and Lower Guinea have been isolated for over 2 million years, morphological divergence appears to be driven more by habitat differences than geographic isolation and suggests that selection in parapatry may be more important than geographic isolation in causing adaptive divergence in morphology.
|
2,338,205 |
European surveillance study on the antibiotic susceptibility of Propionibacterium acnes.
|
Propionibacterium acnes strains are recovered from infections linked to surgical procedures, foreign bodies and septicaemia. This study investigated the antibiotic susceptibility patterns of P. acnes isolates from different systemic infections and determined the genomic diversity among resistant P. acnes isolates with low-frequency restriction analysis of chromosomal DNA by pulsed-field gel electrophoresis (PFGE). In total, 304 P. acnes isolates from 13 laboratories in 13 European countries were tested against six antimicrobial agents by the NCCLS reference agar dilution method and the breakpoints recommended by the European Committee on Antimicrobial Susceptibility Testing. Blood isolates were encountered most frequently, followed by those from skin and soft tissue infections, and abdominal infections. Of the isolates examined, 2.6% were resistant to tetracycline, 15.1% to clindamycin, and 17.1% to erythromycin. No resistance was observed to linezolid, benzylpenicillin or vancomycin. There was considerable variation between countries in the proportion of resistant strains, ranging from 83% in Croatia and 60% in Italy to 0% in The Netherlands. Isolates from blood were predominant among the resistant isolates. Seventeen clones and 78 banding patterns were identified among the resistant isolates. It was concluded that antimicrobial resistance has now emerged among P. acnes isolates from systemic infections.
|
2,338,206 |
The clinical utility of genetic information in the care of persons with Alzheimer's disease.
|
Genetic research about Alzheimer's disease (AD) is advancing quickly, but the clinical utility of these gene discoveries remains unclear. The clinical context of genetic research in AD is discussed.
|
2,338,207 |
Host factors in occupational diisocyanate asthma: a Swiss longitudinal study.
|
To investigate the usefulness of surrogates for individual susceptibility to organic diisocyanates in occupational asthma.</AbstractText>All new cases declared to the Swiss National Accident Insurance Company (SUVA) for establishment of a case for compensable occupational disease during 1993. Sixty-nine persons, of whom three were women, were suspected of having occupational asthma due to isocyanates. Of these, 47 subjects fulfilled the criteria to be accepted as an occupational disease case.</AbstractText>All subjects were studied clinically and gave a blood sample for the phenotyping of their alpha-antitrypsin status and for immunological studies. The subjects were also given a peroral dose of caffeine for the determination of their N-acetylation capacity. Finally, those with an occupational disease were subjected to the methacholine provocation test.</AbstractText>Forty-four persons with occupational disease, out of 47, were heterozygous antitrypsin carriers and/or slow acetylators of primary amines. In the bronchial provocation with methacholine, 12 of these subjects had an unaltered response and seven had a mild reaction, 13 a moderate one and 15 a severe reaction.</AbstractText>The study confirms the finding that slow N-acetylators are susceptible to asthma from exposure to common diisocyanate monomers at work. The same applies to heterozygous antitrypsin-phenotype carriers. Thus, the use of these markers may reinforce the diagnostic procedure, but they cannot completely replace the immunological tests.</AbstractText>
|
2,338,208 |
Systematic follow-up and case management of the abnormal newborn screen can improve acceptance of genetic counseling for sickle cell or other hemoglobinopathy trait.
|
Sickle cell or other hemoglobinopathy trait detected on the newborn screen provides an opportunity for genetic counseling of families at risk of having a child with a major hemoglobinopathy. However, follow-up of hemoglobinopathy trait is often fragmented and acceptance of counseling is low. We describe the results of systematic follow-up and case management of abnormal newborn screen and the effect on acceptance of counseling.</AbstractText>From July 1997 to June 2002, families of a newborn with hemoglobinopathy trait were notified by mail. In April 2003, an intensive trait follow-up protocol including letters, telephone calls, educational videos, and genetic counseling was implemented. Demographic information and follow-up activity were documented and tracked using an electronic database.</AbstractText>From July 1997 to June 2002, 3095 families were notified by letter of a newborn with hemoglobinopathy trait and were offered genetic counseling. Of these, 165 (5.3%) received counseling by telephone and 60 (2%) underwent extended family testing. From April to December 2003, 694 families with a newborn with hemoglobinopathy trait were notified by mail. Of these, 362 (52%) families were reached by telephone. Of those contacted by telephone, 92% received genetic counseling via telephone, 57% were interested in family testing, and 12% scheduled an appointment. Additionally, 27% of families were mailed an educational video. Among those declining extended family testing, 26% preferred to consult their pediatrician.</AbstractText>Systematic follow-up and case management of abnormal newborn screen can improve the acceptance of genetic counseling.</AbstractText>
|
2,338,209 |
Application of ROMA (representational oligonucleotide microarray analysis) to patients with cytogenetic rearrangements.
|
To demonstrate the accuracy and sensitivity of Representational Oligonucleotide Microarray Analysis (ROMA) to describe copy number changes in patients with chromosomal abnormalities.</AbstractText>ROMA was performed using BglII digested DNA from two cases with cytogenetically detected deletions and one case with an unbalanced terminal rearrangement detected only by subtelomeric FISH. Hybridization was to an 85,000-probe oligonucleotide microarray, providing an average resolution of 35 kb. FISH was used to confirm some of the ROMA findings.</AbstractText>By ROMA, a del(13)(q14.3q21.2) was shown to be noncontiguous, with deletions extending from 53.08 to 61.40 Mb and from 72.88 to 74.83 Mb. The 10-Mb deletion contained only six known genes. FISH confirmed the noncontiguous nature of the deletion, as well as a small amplification in 6q that was also found in the patient's mother. A del(4)(q12q21.2) was found by ROMA to be 23 Mb in length, from 58.8 to 81.9 Mb on chromosome 4, in agreement with the cytogenetically assigned breakpoints. ROMA showed that an unbalanced "subtelomeric" rearrangement involved a 6-Mb deletion of 22q and an 8-Mb duplication of 16q.</AbstractText>ROMA can define cytogenetic aberrations with extraordinary precision. Unexpected findings included the interrupted nature of the deletion in 13q and the large size of the imbalances in the "subtelomeric" rearrangement. Together with the information from the human genome sequence and proteomics, the ability to define rearrangements with "ultra-high" resolution will improve the ability to provide accurate prognosis both prenatally and postnatally to parents of offspring with chromosomal aberrations.</AbstractText>
|
2,338,210 |
CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis.
|
Two common variant alleles of the cytochrome CYP2C9 (CYP2C9*2 and CYP2C9*3) lead to reduced warfarin metabolism in vitro and in vivo. The study objective was to examine the strength and quality of existing evidence about CYP2C9 gene variants and clinical outcomes in warfarin-treated patients.</AbstractText>The study was a systematic review and meta-analysis. Multiple electronic databases were searched, references identified from bibliographies were sought, and experts and authors of primary studies were also contacted. Strict review inclusion criteria were determined. Three reviewers independently extracted data using prepiloted proformas.</AbstractText>In all, 11 studies meeting review inclusion criteria were identified (3029 patients). Nine were included in the meta-analyses (2775 patients). Random effects meta-analyses were performed; statistical heterogeneity and inconsistency was assessed. Twenty percent of patients studied carry a variant allele: CYP2C9*2 12.2% (9.7%-15.0%) and CYP2C9*3, 7.9% (6.5%-9.7%). Mean difference in daily warfarin dose: for CYP2C9*2, the reduction was 0.85 mg (0.60-1.11 mg), a 17% reduction. For CYP2C9*3, the reduction was 1.92 mg (1.37-2.47 mg), a 37% reduction. For CYP2C9*2 or *3, the reduction was 1.47 mg (1.24-1.71 mg), a 27% reduction. The relative bleeding risk for CYP2C9*2 was 1.91 (1.16-3.17) and for CYP2C9*3 1.77 (1.07-2.91). For either variant, the relative risk was 2.26 (1.36-3.75).</AbstractText>Patients with CYP2C9*2 and CYP2C9*3 alleles have lower mean daily warfarin doses and a greater risk of bleeding. Testing for gene variants could potentially alter clinical management in patients commencing warfarin. Evidence for the clinical utility and cost-effectiveness of genotyping is needed before routine testing can be recommended.</AbstractText>
|
2,338,211 |
Detection of hypermethylated genes in women with and without cervical neoplasia.
|
DNA methylation changes are an early event in carcinogenesis and are often present in the precursor lesions of various cancers. We examined whether DNA methylation changes might be used as markers of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC).</AbstractText>We used methylation-specific polymerase chain reaction (PCR) to analyze promoter hypermethylation of 20 genes, selected on the basis of their role in cervical cancer, in 319 exfoliated cell samples and matched tissue biopsy specimens collected during two studies of Senegalese women with increasingly severe CIN and ICC (histology negative/atypical squamous cells of undetermined significance [ASCUS] = 142, CIN-1 = 39, CIN-2 = 23, CIN-3/carcinoma in situ [CIS] = 23, ICC = 92). Logic regression was used to determine the best set of candidate genes to use as disease markers. All statistical tests were two-sided.</AbstractText>Similar promoter methylation patterns were seen in genes from exfoliated cell samples and corresponding biopsy specimens. For four genes (CDH13, DAPK1, RARB, and TWIST1), the frequency of hypermethylation increased statistically significantly with increasing severity of neoplasia present in the cervical biopsy (P<.001 for each). By using logic regression, we determined that the best panel of hypermethylated genes included DAPK1, RARB, or TWIST1. At least one of the three genes was hypermethylated in 57% of samples with CIN-3/CIS and in 74% of samples with ICC but in only 5% of samples with CIN-1 or less. The estimated specificity of the three-gene panel was 95%, and its sensitivity was 74% (95% confidence interval [CI] = 73% to 75%) for ICC and 52% (95% CI = 49% to 55%) for CIN-3/CIS. By extrapolation, we estimated that, among Senegalese women presenting to community-based clinics, detection of the DAPK1, RARB, or TWIST1 hypermethylated gene would reveal histologically confirmed CIN-3 or worse with a sensitivity of 60% (95% CI = 57% to 63%) and a specificity of 95% (95% CI = 94% to 95%).</AbstractText>Aberrant promoter methylation analysis on exfoliated cell samples is a potential diagnostic tool for cervical cancer screening that potentially may be used alone or in conjunction with cytology and/or human papillomavirus testing.</AbstractText>
|
2,338,212 |
Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.
|
The accurate identification and interpretation of germline mutations in mismatch repair genes in colorectal cancer cases is critical for clinical management. Current data suggest that mismatch repair mutations are highly heterogeneous and that many mutations are not detected when conventional DNA sequencing alone is used.</AbstractText>To evaluate the potential of conversion analysis compared with DNA sequencing alone to detect heterogeneous germline mutations in MLH1, MSH2, and MSH6 in colorectal cancer patients.</AbstractText><AbstractText Label="DESIGN, SETTING, AND PARTICIPANTS" NlmCategory="METHODS">Multicenter study with patients who participate in the Colon Cancer Family Registry. Mutation analyses were performed in participant samples determined to have a high probability of carrying mismatch repair germline mutations. Samples from a total of 64 hereditary nonpolyposis colorectal cancer cases, 8 hereditary nonpolyposis colorectal cancer-like cases, and 17 cases diagnosed prior to age 50 years were analyzed from June 2002 to June 2003.</AbstractText>Classification of family members as carriers or noncarriers of germline mutations in MLH1, MSH2, or MSH6; mutation data from conversion analysis compared with genomic DNA sequencing.</AbstractText>Genomic DNA sequencing identified 28 likely deleterious exon mutations, 4 in-frame deletion mutations, 16 missense changes, and 22 putative splice site mutations. Conversion analysis identified all mutations detected by genomic DNA sequencing--plus an additional exon mutation, 12 large genomic deletions, and 1 exon duplication mutation--yielding an increase of 33% (14/42) in diagnostic yield of deleterious mutations. Conversion analysis also showed that 4 of 16 missense changes resulted in exon skipping in transcripts and that 17 of 22 putative splice site mutations affected splicing or mRNA transcript stability. Conversion analysis provided an increase of 56% (35/63) in the diagnostic yield of genetic testing compared with genomic DNA sequencing alone.</AbstractText>The data confirm the heterogeneity of mismatch repair mutations and reveal that many mutations in colorectal cancer cases would be missed using conventional genomic DNA sequencing alone. Conversion analysis substantially increases the diagnostic yield of genetic testing for mismatch repair mutations in patients diagnosed as having colorectal cancer.</AbstractText>
|
2,338,213 |
Carrier screening for alpha- and beta-thalassemia in pregnancy: the results of an 11-year prospective program in Guangzhou Maternal and Neonatal hospital.
|
To evaluate the first prospective screening program in China for control of alpha and beta-thalassemia in the population of pregnant couples.</AbstractText>During the period between January 1993 and December 2003, a hospital-based preventive program was conducted at the biggest birth center in Guangzhou, with 1/17 of all deliveries in this city referred annually by use of conventional heterozygote screening strategy in combination with the system of regular healthcare examination in pregnancy.</AbstractText>The screened records included 49 221 pregnant women, and 4503 husbands of the pregnant women showed positive on the screening test. Of the at-risk couples, there were 198 for alpha-thal (4.4%) and 83 for beta-thal (1.8%), respectively. Genetic counseling was offered to all at-risk couples and a successful prenatal diagnosis was performed for 269 out of 281 (95.7%) for alpha- or beta-thal major, with the remaining 12 couples refusing to accept prenatal diagnosis. Out of 187 pregnancies at risk for homozygous alpha0-thal and 82 at risk for beta-thal major, 51 hydrops fetalis with Hb Bart's and 18 beta-thal major were identified. All pregnancies with affected fetuses were voluntarily terminated, leading to a marked reduction of severe alpha- and beta-thal births at this hospital since the program has been launched.</AbstractText>Our hospital-based program proved to be highly effective in reducing severe thals in pregnant populations.</AbstractText>Copyright 2005 John Wiley & Sons, Ltd.</CopyrightInformation>
|
2,338,214 |
EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma.
|
Clear cell sarcoma (CCS) is classically a deep soft tissue tumor associated with tendons or aponeuroses, although cases of primary CCS of the gastrointestinal (GI) tract have recently been reported. Because it is difficult to distinguish CCS from metastatic melanoma based on morphology, immunohistochemical profile, and ultrastructural features, it is possible that some GI tumors diagnosed as metastatic melanoma actually represent primary GI CCS. Because the EWS-ATF1 fusion transcript and the associated t(12;22)(q13;q12) translocation occur in CCS but not cutaneous melanoma, we investigated the use of molecular-based testing for discriminating CCS from metastatic melanoma (MM) in GI tumors.</AbstractText>Patients with GI tumors diagnosed as MM were identified from departmental files. The tumors were tested for the EWS-ATF1 fusion transcript by RT-PCR and for t(12;22)(q13;q12) by fluorescence in situ hybridization.</AbstractText>Detailed review of medical records revealed that 16 (80%) of the 20 had a documented history of cutaneous melanoma. Two cases (10%) harbored the EWS-ATF1 fusion transcript, and fluorescence in situ hybridization confirmed the presence of t(12;22) in both cases. Of the 2 positive tumors, 1 developed in a patient who had no history of cutaneous melanoma, and the other developed in a patient with a remote history of vulvar melanoma.</AbstractText>Based on molecular genetic findings, a subset of GI tumors diagnosed as MM by routine histopathologic evaluation represents CCS.</AbstractText>
|
2,338,215 |
Gastroenteritis in US Marines during Operation Iraqi Freedom.
|
Approximately 83,000 US Marines participated in the opening phase of Operation Iraqi Freedom in Spring 2003. A Navy Preventive Medicine laboratory was set up in Ad Diwaniyah, Iraq, to provide clinical diagnostic support for Marine medical units during a period of repositioning in south-central Iraq.</AbstractText>Specimen collection boxes were sent to >30 primary care medical stations handling 500-900 personnel each. The laboratory had capability to detect many different disease agents, especially those causing febrile illness. Diarrheal stool diagnostic evaluation included plating and biochemical identification, antigen serologic testing, fluorescent antibody antigen detection, disk diffusion antimicrobial susceptibility testing, enzyme immunoassay, and reverse-transcriptase polymerase chain reaction for norovirus (NV). Confirmation and sequencing work for NV was done at Cincinnati Children's Hospital Medical Center (Ohio).</AbstractText>By far the most common reason for infectious disease sick call visits was gastrointestinal illness; no other symptoms had equivalent impact. An enteropathogen was detected in 57 (44%) of 129 stool samples, with NV detected in 30 stool samples (23%) obtained from 14 different battalion or similar-sized units; next in frequency were Shigella flexneri and Shigella sonnei, which were isolated from 26 stool samples (20%) obtained from 15 units. Sequencing the NV RNA polymerase gene demonstrated that NV strains represented 7 genetic clusters, including 2 strains from genogroup I and 5 from genogroup II. Ciprofloxacin was effective in vitro against most bacterial agents, but neither doxycyline (which was taken daily as the antimalarial prophylaxis dose) nor trimethoprim-sulfamethoxazole were effective.</AbstractText>Multiple strains of Shigella species and NV predominated, probably because they do not require a large inoculum to cause infection. Otherwise, personnel remained free of infectious illness during this phase of the conflict, because other infectious agents were rare or absent.</AbstractText>
|
2,338,216 |
Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease.
|
Integration of genome-wide expression profiling with linkage analysis is a new approach to identifying genes underlying complex traits. We applied this approach to the regulation of gene expression in the BXH/HXB panel of rat recombinant inbred strains, one of the largest available rodent recombinant inbred panels and a leading resource for genetic analysis of the highly prevalent metabolic syndrome. In two tissues important to the pathogenesis of the metabolic syndrome, we mapped cis- and trans-regulatory control elements for expression of thousands of genes across the genome. Many of the most highly linked expression quantitative trait loci are regulated in cis, are inherited essentially as monogenic traits and are good candidate genes for previously mapped physiological quantitative trait loci in the rat. By comparative mapping we generated a data set of 73 candidate genes for hypertension that merit testing in human populations. Mining of this publicly available data set is expected to lead to new insights into the genes and regulatory pathways underlying the extensive range of metabolic and cardiovascular disease phenotypes that segregate in these recombinant inbred strains.
|
2,338,217 |
Prenatal testing guidelines: time for a new approach.
|
Numerous advances over the past 15 years have led to a much wider array of prenatal testing options for pregnant women who are interested in obtaining information regarding the chromosomal status of their fetus. However, despite recent data calling into question the assumptions underlying current testing guidelines, including those inherent in the risk-based threshold for offering invasive testing, chorionic villus sampling and amniocentesis are still typically offered only to women whose likelihood of carrying a fetus affected by a chromosomal disorder such as Down syndrome is at least as high as that of the average 35-year-old. In this paper, we summarize the evidence suggesting that this aspect of prenatal testing guidelines should be revisited, and that women should be allowed to make informed decisions regarding the use of invasive testing that are reflective of their own values and preferences.
|
2,338,218 |
[SSCP analysis (ITS2, ERG11) in clinical Candida isolates from oral cavity in oncology patients].<Pagination><StartPage>182</StartPage><EndPage>186</EndPage><MedlinePgn>182-6</MedlinePgn></Pagination><Abstract><AbstractText>Antifungal prophylactic therapy in oncology patients has favors the emergence of diverse species of Candida. In the present study 32 clinic isolates of Candida spp., recovered from oral cavity, were evaluated testing their susceptibility to diverse antifungals by means of the microdilution method according with the document M-27A of the National Committee for Clinical Laboratory Standards (NCCLS). The response to antifungals was then compared with SSCP patterns of the gene ERG11, hoping to find mutations in this gene linked to resistance to the azole antifungals from samples of clinical origin. Three SSCP genotypes with diverse response to different antifungals were found. This study suggested that a link of mutations in the ERG11 gene of Candida albicans and antifungal resistance was not supported by this data. In addition, the isolates were also classified by conventional methods and their genetic diversity evaluated by means of SSCP analysis and evaluation of their ITS2 regions, identifying eight SSCP genotypes. This technique has the potential to be a more sensitive method for taxonomic classification.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Díaz-López</LastName><ForeName>Mónica María</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>Instituto de Biotechnología, Facultad de Agronomía, Universidad Nacional de Colombia, Bogota, Colombia. [email protected]</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oliveros-Garay</LastName><ForeName>Oscar Arturo</ForeName><Initials>OA</Initials></Author><Author ValidYN="Y"><LastName>Orozco-Diaz</LastName><ForeName>Oscar</ForeName><Initials>O</Initials></Author></AuthorList><Language>spa</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><VernacularTitle>Análisis SSCP (ITS2, ERG11) de aislamientos clínicos de Candida spp. de cavidad oral en pacientes oncológicos.</VernacularTitle></Article><MedlineJournalInfo><Country>Spain</Country><MedlineTA>Rev Iberoam Micol</MedlineTA><NlmUniqueID>9425531</NlmUniqueID><ISSNLinking>1130-1406</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C548418">CYP51A1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004271">DNA, Fungal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D021903">DNA, Ribosomal Spacer</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005656">Fungal Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012331">RNA, Fungal</NameOfSubstance></Chemical><Chemical><RegistryNumber>9035-51-2</RegistryNumber><NameOfSubstance UI="D003577">Cytochrome P-450 Enzyme System</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.-</RegistryNumber><NameOfSubstance UI="D010088">Oxidoreductases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.154</RegistryNumber><NameOfSubstance UI="D058886">Sterol 14-Demethylase</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002175" MajorTopicYN="N">Candida</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002180" MajorTopicYN="N">Candidiasis, Oral</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003577" MajorTopicYN="N">Cytochrome P-450 Enzyme System</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004271" MajorTopicYN="N">DNA, Fungal</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D021903" MajorTopicYN="N">DNA, Ribosomal Spacer</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005656" MajorTopicYN="N">Fungal Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016867" MajorTopicYN="N">Immunocompromised Host</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009055" MajorTopicYN="N">Mouth</DescriptorName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009369" MajorTopicYN="N">Neoplasms</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009894" MajorTopicYN="N">Opportunistic Infections</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010088" MajorTopicYN="N">Oxidoreductases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018807" MajorTopicYN="Y">Polymorphism, Single-Stranded Conformational</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012331" MajorTopicYN="N">RNA, Fungal</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D021521" MajorTopicYN="N">Ribotyping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058886" MajorTopicYN="N">Sterol 14-Demethylase</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2005</Year><Month>2</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2005</Year><Month>4</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2005</Year><Month>2</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">15709797</ArticleId><ArticleId IdType="pii">200421182</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="KIE"><PMID Version="1">15709287</PMID><DateCompleted><Year>2005</Year><Month>06</Month><Day>14</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><JournalIssue CitedMedium="Print"><PubDate><Year>2002</Year><Month>Sep</Month><Day>05</Day></PubDate></JournalIssue><Title>Duke law and technology review</Title><ISOAbbreviation>Duke Law Technol Rev</ISOAbbreviation></Journal>Genetic testing in the workplace: the employer's coin toss.
|
Antifungal prophylactic therapy in oncology patients has favors the emergence of diverse species of Candida. In the present study 32 clinic isolates of Candida spp., recovered from oral cavity, were evaluated testing their susceptibility to diverse antifungals by means of the microdilution method according with the document M-27A of the National Committee for Clinical Laboratory Standards (NCCLS). The response to antifungals was then compared with SSCP patterns of the gene ERG11, hoping to find mutations in this gene linked to resistance to the azole antifungals from samples of clinical origin. Three SSCP genotypes with diverse response to different antifungals were found. This study suggested that a link of mutations in the ERG11 gene of Candida albicans and antifungal resistance was not supported by this data. In addition, the isolates were also classified by conventional methods and their genetic diversity evaluated by means of SSCP analysis and evaluation of their ITS2 regions, identifying eight SSCP genotypes. This technique has the potential to be a more sensitive method for taxonomic classification.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Díaz-López</LastName><ForeName>Mónica María</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>Instituto de Biotechnología, Facultad de Agronomía, Universidad Nacional de Colombia, Bogota, Colombia. [email protected]</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oliveros-Garay</LastName><ForeName>Oscar Arturo</ForeName><Initials>OA</Initials></Author><Author ValidYN="Y"><LastName>Orozco-Diaz</LastName><ForeName>Oscar</ForeName><Initials>O</Initials></Author></AuthorList><Language>spa</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><VernacularTitle>Análisis SSCP (ITS2, ERG11) de aislamientos clínicos de Candida spp. de cavidad oral en pacientes oncológicos.</VernacularTitle></Article><MedlineJournalInfo><Country>Spain</Country><MedlineTA>Rev Iberoam Micol</MedlineTA><NlmUniqueID>9425531</NlmUniqueID><ISSNLinking>1130-1406</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C548418">CYP51A1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004271">DNA, Fungal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D021903">DNA, Ribosomal Spacer</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005656">Fungal Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012331">RNA, Fungal</NameOfSubstance></Chemical><Chemical><RegistryNumber>9035-51-2</RegistryNumber><NameOfSubstance UI="D003577">Cytochrome P-450 Enzyme System</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.-</RegistryNumber><NameOfSubstance UI="D010088">Oxidoreductases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.14.154</RegistryNumber><NameOfSubstance UI="D058886">Sterol 14-Demethylase</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002175" MajorTopicYN="N">Candida</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002180" MajorTopicYN="N">Candidiasis, Oral</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003577" MajorTopicYN="N">Cytochrome P-450 Enzyme System</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004271" MajorTopicYN="N">DNA, Fungal</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D021903" MajorTopicYN="N">DNA, Ribosomal Spacer</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005656" MajorTopicYN="N">Fungal Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016867" MajorTopicYN="N">Immunocompromised Host</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009055" MajorTopicYN="N">Mouth</DescriptorName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009369" MajorTopicYN="N">Neoplasms</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009894" MajorTopicYN="N">Opportunistic Infections</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000382" MajorTopicYN="Y">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010088" MajorTopicYN="N">Oxidoreductases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018807" MajorTopicYN="Y">Polymorphism, Single-Stranded Conformational</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012331" MajorTopicYN="N">RNA, Fungal</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D021521" MajorTopicYN="N">Ribotyping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058886" MajorTopicYN="N">Sterol 14-Demethylase</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2005</Year><Month>2</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2005</Year><Month>4</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2005</Year><Month>2</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">15709797</ArticleId><ArticleId IdType="pii">200421182</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="KIE"><PMID Version="1">15709287</PMID><DateCompleted><Year>2005</Year><Month>06</Month><Day>14</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><JournalIssue CitedMedium="Print"><PubDate><Year>2002</Year><Month>Sep</Month><Day>05</Day></PubDate></JournalIssue><Title>Duke law and technology review</Title><ISOAbbreviation>Duke Law Technol Rev</ISOAbbreviation></Journal><ArticleTitle>Genetic testing in the workplace: the employer's coin toss.</ArticleTitle><Pagination><StartPage>E1</StartPage><MedlinePgn>E1</MedlinePgn></Pagination><Abstract>A toss of the coin by the modern-day employer reveals two options regarding genetic testing in the workplace. The employer may choose to take advantage of increasingly precise, available, and affordable genetic testing in order to ascertain the genetic characteristics--and deficiencies--of its employees. This outcome exposes the employer to a vast array of potential litigation and liability relating to the Americans with Disabilities Act, the Fourth Amendment, Title VII of the Civil Rights Act, and state legislation designed to protect genetic privacy. Alternatively, the employer may neglect to indulge in this trend of genetic testing and may face liability for employer negligence, violations of federal legislation such as OSHA regulations, and increased costs associated with insuring the health of genetically endangered employees. In the rapidly developing universe of genetic intelligence, the employer is faced with a staggering dilemma.
|
2,338,219 |
Hereditary cancer syndromes of the skin.
|
Hereditary cancer syndromes are a group of disorders characterized by a genetic susceptibility to the development of malignant tumors. Multiple cancers in the family or an abnormally early onset for the given cancer may suggest an underlying inherited predisposition. Awareness of their associated dermatologic manifestations can facilitate early detection of risk for neoplasms. This article provides an update on the clinical features, diagnostic criteria, and the use of genetic analysis in the detection of causative mutations of those hereditary cancer syndromes with cutaneous manifestations.
|
2,338,220 |
The phakomatoses.
|
The "phakomatosis" concept was formulated early in the twentieth century by the ophthalmologist van der Hoeve. He included 3 disorders in the group-neurofibromatosis, tuberous sclerosis complex, and von Hippel-Lindau syndrome--on the basis of the occurrence of patchy ophthalmologic manifestations in each disorder. Since the name was coined, much has been learned about the pathogenesis of these 3 disorders. It is clear that 2 of them--neurofibromatosis and tuberous sclerosis--are collective terms for multiple disorders. Each of the conditions is caused by distinct genetic defects, with little commonality in terms of protein function. Yet, in some respects, the disorders share a pathogenetic mechanism, that of the tumor suppressor gene. This review will briefly describe these disorders in light of what has been learned about underlying molecular pathogenesis. In each case, genetic testing is beginning to be available; principles of the use of genetic tests will be described.
|
2,338,221 |
Association of the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase gene with schizophrenia in the Chinese Han population.
|
Several independent linkage studies have demonstrated that the 1q22 region is likely to harbor candidate schizophrenia susceptibility genes. Recently, some genetic variants within CAPON have been reported as exhibiting significant linkage disequilibrium to schizophrenia in Canadian familial-schizophrenia pedigrees. We examined nine single nucleotide polymorphisms (SNPs), which span an approximately 236-kb region of CAPON, in 664 schizophrenia cases and 941 controls in the Chinese Han population. We detected a significant difference in allele distributions of SNP rs348624 (P = 0.000017). Moreover, the overall frequency of haplotypes constructed from three SNPs including rs348624 showed significant difference between cases and controls (P = 0.000025). Our findings indicate that CAPON gene may be a candidate susceptibility gene for schizophrenia in Chinese Han population, and also provide further support for the potential importance of NMDAR-mediated glutamatergic transmission in the etiology of schizophrenia.
|
2,338,222 |
Plants used to treat epilepsy by Tanzanian traditional healers.
|
A cross-sectional study performed in Temeke District (Dar es Salaam, Tanzania) showed that 5.5% of the traditional healers have knowledge for the treatment of epilepsy. Of the 100 healers interviewed, 30 (30%) believed that epilepsy was caused by witchcraft, while 19 (19%) thought epilepsy has a genetic origin which can be inherited. Other healers thought epilepsy can be caused by head injury or malaria (24%), and the remaining 27% did not know the cause. Most of the healers (92%) could present an accurate account on the symptoms of the disease, including dizziness, loss of consciousness, abrupt falling down, frothing from the mouth, loss of memory, biting of the tongue, confusion, and restlessness. They showed competence in the treatment of the disease, whereby 60 plants that are commonly used were mentioned. Abrus precatorius L. (Leguminosae), Clausena anisata (Willd.) Oliv. (Rutaceae) and Hoslundia opposita Vahl (Lamiaceae), which are among the plants mentioned, have proven anticonvulsant activity, while a few other species on their list have been reported to be useful in the treatment of epilepsy. Biological testing of these plants, using different models of convulsions is, suggested.
|
2,338,223 |
Reduced variation among northern deer tick populations at an autosomal microsatellite locus.
|
To determine whether genes flow freely between populations of the Ixodes ricinus-like ticks of eastern North America, and to determine whether the abundant northerly populations of these vectors of Lyme disease and other zoonotic infections may have arisen recently from a small cohort of ancestral founders, we characterized the nuclear IR27 microsatellite alleles in ticks sampled from the geographic extremes of their ranges. These microsatellite alleles differentiated populations located in the southeastern, northcentral and northeastern United States, respectively. Although evident heterozygous genotypes are about as frequent as would be expected in randomly mating populations, particular microsatellite alleles and diploid genotypes occur more frequently in certain populations than in others. Ticks from the Northeast and upper Midwest are markedly more related to each other than to ticks from the Southeast. Patterns of diversity present in this nuclear microsatellite marker correspond to those evident at a mitochondrial locus and indicate that the deer ticks of the Northeast and upper Midwest are genetically isolated from those in the Southeast. The Ixodes ricinus-like ticks that impose a public health burden in the northeastern and northcentral United States originated recently in a common founder population.
|
2,338,224 |
Algorithm for efficient PKHD1 mutation screening in autosomal recessive polycystic kidney disease (ARPKD).
|
Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of childhood renal- and liver-related morbidity and mortality with variable disease expression. While most cases manifest peri-/neonatally with a high mortality rate in the first month of life, others survive to adulthood. ARPKD is caused by mutations in the Polycystic Kidney and Hepatic Disease 1 (PKHD1) gene on chromosome 6p12. PKHD1 is an exceptionally large gene (470 kb) with a longest open reading frame transcript of 67 exons predicted to encode a 4,074-amino acid (aa) (447 kDa) multidomain integral membrane protein (fibrocystin/polyductin) of unknown function. Recent DHPLC-based mutational studies have reported detection rates of about 80% and a minimum of one PKHD1 mutation in more than 95% of families. Thus far, a total of 263 different PKHD1 mutations (639 mutated alleles) are included in the locus-specific database (www.humgen.rwth-aachen.de). Except for a few population-specific founder alleles and the common c.107C>T (p.Thr36Met) missense change, PKHD1 is characterized by significant allelic diversity, making mutation screening time-consuming and labor-intensive. Mutations are distributed throughout the gene's coding sequence; however, they are not equally scattered. Thus, we aimed to set up an algorithm for efficient molecular genetic diagnostics in ARPKD. A total of 80% of known PKHD1 mutations can be identified if a subset of 27 out of 77 DHPLC fragments is screened. The current study provides an essential platform for PKHD1 mutation screening in a routine setting that will largely alleviate molecular genetic diagnostics in patients suspected to have ARPKD.
|
2,338,225 |
Computational prediction of operons in Synechococcus sp. WH8102.
|
We computationally predict operons in the Synechococcus sp. WH8102 genome based on three types of genomic data: intergenic distances, COG gene functions and phylogenetic profiles. In the proposed method, we first estimate a log-likelihood distribution for each type of genomic data, and then fuse these distribution information by a perceptron to discriminate pairs of genes within operons (WO pairs) from those across transcription unit borders (TUB pairs). Computational experiments demonstrated that WO pairs tend to have shorter intergenic distances, a higher probability being in the same COG functional categories and more similar phylogenetic profiles than TUB pairs, indicating their powerful capabilities for operon prediction. By testing the method on 236 known operons of Escherichia coli K12, an overall accuracy of 83.8% is obtained by joint learning from multiple types of genomic data, whereas individual information source yields accuracies of 80.4%, 74.4%, and 70.6% respectively. We have applied this new approach, in conjunction with our previous comparative genome analysis-based approach, to predict 556 (putative) operons in WH8102. All predicted data are available at (http://www.cs.ucr.edu/~xin/operons.htm) for public use.
|
2,338,226 |
Learning from peer assessment: the role of the external quality assurance multilaboratory thrombophilia test process.
|
The quality control process is a critical feature of pathology best practice. In addition to internal quality control processes applied on a test-to-test or day-to-day basis, the participation of laboratories in external quality assurance programs (QAPs) is critical to achieving ongoing test accuracy. There are several such programs operating in the international arena. With respect to thrombophilia, these include the Australia-based Royal College of Pathologists of Australia QAP, the United Kingdom-based National External Quality Assessment Service, and the International Thrombophilia External Quality Assessment Scheme, based in the Netherlands. Although there are some similarities between the programs, some diversity is also apparent. Each of the programs assess for the common markers of congenital thrombophilia, such as antithrombin, protein C, protein S, and activated protein C resistance. Testing of some acquired markers of thrombophilia, such as lupus anticoagulant, and genetic tests such as factor V Leiden and prothrombin G20210A mutation, are also available. This report focuses on some recent trends from these programs.
|
2,338,227 |
Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness at 10 years of age.
|
We sought to identify early life factors (ie, first 4 years) associated with wheeze, asthma, and bronchial hyperresponsiveness (BHR) at age 10 years, comparing their relative influence for these conditions.</AbstractText>Children were seen at birth, and at 1, 2, 4, and 10 years of age in a whole-population birth cohort study (1,456 subjects). Information was collected prospectively on genetic and environmental risk factors. Skin-prick testing was performed at 4 years of age. Current wheeze (in the last 12 months) and currently diagnosed asthma (CDA) [ie, current wheeze and ever-diagnosed asthmatic subject] were recorded at 10 years of age when BHR was measured at bronchial challenge. Independent significant risk factors for these outcomes were identified by logistic regression.</AbstractText>Independent significance for current wheeze occurred with maternal asthma (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.27 to 3.41) and paternal asthma (OR, 2.12; 95% CI 1.29 to 3.51), recurrent chest infections at 2 years (OR, 3.98; 95% CI, 2.36 to 6.70), atopy at 4 years of age (OR, 3.69; 95% CI, 2.36 to 5.76), eczema at 4 years of age (OR, 2.15; 95% CI, 1.24 to 3.73), and parental smoking at 4 years of age (OR, 2.18; 95% CI, 1.25 to 3.81). For CDA, significant factors were maternal asthma (OR, 2.26; 95% CI, 1.24 to 3.73), paternal asthma (OR, 2.30; 95% CI, 1.17 to 4.52), and sibling asthma (OR, 2.00; 95% CI, 1.16 to 3.43), recurrent chest infections at 1 year of age (OR, 2.67; 95% CI, 1.12 to 6.40) and 2 years of age (OR, 4.11; 95% CI, 2.06 to 8.18), atopy at 4 years of age (OR, 7.22; 95% CI, 4.13 to 12.62), parental smoking at 1 year of age (OR, 1.99; 95% CI, 1.15 to 3.45), and male gender (OR, 1.72; 95% CI, 1.01 to 2.95). For BHR, atopy at 4 years of age (OR, 5.38; 95% CI, 3.06 to 9.47) and high social class at birth (OR, 2.03; 95% CI, 1.16 to 3.53) proved to be significant.</AbstractText>Asthmatic heredity, predisposition to early life atopy, plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age. BHR at 10 years of age has a narrower risk profile, suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR.</AbstractText>
|
2,338,228 |
Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT.
|
We conducted linkage analysis of 80 candidate genes in 201 brother pairs affected with prostatic adenocarcinoma. Markers representing two adjacent candidate genes on chromosome 3p, CDC25A and FHIT, showed suggestive evidence for linkage with single-point identity-by-descent allele-sharing statistics. Fine-structure multipoint linkage analysis yielded a maximum LOD score of 3.17 (P = 0.00007) at D3S1234 within FHIT intron 5. For a subgroup of 38 families in which three or more affected brothers were reported, the LOD score was 3.83 (P = 0.00001). Further analysis reported herein suggested a recessive mode of inheritance. Association testing of 16 single nucleotide polymorphisms (SNP) spanning a 381-kb interval surrounding D3S1234 in 202 cases of European descent with 143 matched, unrelated controls revealed significant evidence for association between case status and the A allele of single nucleotide polymorphism rs760317, located within intron 5 of FHIT (Pearson's chi(2) = 8.54, df = 1, P = 0.0035). Our results strongly suggest involvement of germline variations of FHIT in prostate cancer risk.
|
2,338,229 |
Estimating cancer survival and clinical outcome based on genetic tumor progression scores.
|
In cancer research, prediction of time to death or relapse is important for a meaningful tumor classification and selecting appropriate therapies. Survival prognosis is typically based on clinical and histological parameters. There is increasing interest in identifying genetic markers that better capture the status of a tumor in order to improve on existing predictions. The accumulation of genetic alterations during tumor progression can be used for the assessment of the genetic status of the tumor. For modeling dependences between the genetic events, evolutionary tree models have been applied.</AbstractText>Mixture models of oncogenetic trees provide a probabilistic framework for the estimation of typical pathogenetic routes. From these models we derive a genetic progression score (GPS) that estimates the genetic status of a tumor. GPS is calculated for glioblastoma patients from loss of heterozygosity measurements and for prostate cancer patients from comparative genomic hybridization measurements. Cox proportional hazard models are then fitted to observed survival times of glioblastoma patients and to times until PSA relapse following radical prostatectomy of prostate cancer patients. It turns out that the genetically defined GPS is predictive even after adjustment for classical clinical markers and thus can be considered a medically relevant prognostic factor.</AbstractText>Mtreemix, a software package for estimating tree mixture models, is freely available for non-commercial users at http://mtreemix.bioinf.mpi-sb.mpg.de. The raw cancer datasets and R code for the analysis with Cox models are available upon request from the corresponding author.</AbstractText>
|
2,338,230 |
Taskforce 9: the application of preimplantation genetic diagnosis for human leukocyte antigen typing of embryos.
|
This 9th statement of the ESHRE Taskforce on Ethics and Law considers ethical questions and specific dilemmas concerning preimplantation genetic diagnosis for human leukocyte antigen typing of embryos. This application is particularly complex because the interests of the sick child needing a transplantation should be balanced against the interests of the future donor child who may result from the technique. It is concluded that, if parents intend to love the child, the creation and use as a donor is not inherently disrespectful.
|
2,338,231 |
Mutations in the human BOULE gene are not a major cause of impaired spermatogenesis.
|
Mutation screening of the BOULE gene in 156 men with azoospermia or severe oligozoospermia revealed no relevant mutations; thus, mutations in BOULE can be eliminated as a major cause of impaired spermatogenesis.
|
2,338,232 |
A novel missense mutation P1290S at exon-20 of the CFTR gene in a Portuguese patient with congenital bilateral absence of the vas deferens.
|
To report a novel cystic fibrosis transmembrane conductance regulator (CFTR) gene missense mutation in a compound heterozygote with congenital bilateral absence of the vas deferens (CBAVD).</AbstractText>Descriptive, controlled study.</AbstractText>Tertiary academic hospital genetics laboratory and private in vitro fertilization (IVF) clinic.</AbstractText><AbstractText Label="PATIENT(S)" NlmCategory="METHODS">One 46-year-old man with CBAVD and no clinical cystic fibrosis (CF) phenotype as indicated by the advanced age at diagnosis, absence of chronic airways and gastrointestinal disease, and normal pancreatic function and sweat chloride concentration. Genomic blood DNA from the patient's parents was analyzed to perform family studies, and 109 fertile men, 32 patients with CBAVD, 15 children carriers of one CFTR mutation, and 5 patients with CF were used to rule out polymorphism.</AbstractText><AbstractText Label="INTERVENTION(S)" NlmCategory="METHODS">Clinical evaluation and treatment, genetical screenings.</AbstractText><AbstractText Label="MAIN OUTCOME MEASURE(S)" NlmCategory="METHODS">Clinical data, biochemical assays, spermiogram analysis, testicle biopsy, intracytoplasmic sperm injection (ICSI) outcome, and CFTR whole gene mutation screening and IVS8T polymorphism.</AbstractText><AbstractText Label="RESULT(S)" NlmCategory="RESULTS">The DNA analysis revealed a 7T/7T homozygote at IVS8-T, with a 4000C-->T change (P1290S) in exon 20 of the CFTR gene, which was inherited from the patient's father. It was associated with a 3272-26A-->G mutation in the other allele that was inherited from his mother.</AbstractText><AbstractText Label="CONCLUSION(S)" NlmCategory="CONCLUSIONS">The novel P1290S missense CFTR mutation causes an amino acid change in a highly conserved region of the CFTR protein that controls channel opening. Pathogenicity is suggested by development of CBAVD in association with a mild CFTR mutation.</AbstractText>
|
2,338,233 |
Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages.
|
To determine the aneuploidy rate in embryos of women with idiopathic recurrent miscarriages and to evaluate whether preimplantation genetic diagnosis for aneuploidy screening could be a feasible approach to improve the possibility of successful pregnancy in these couples.</AbstractText>Prospective cohort study.</AbstractText>Tertiary university referral center.</AbstractText><AbstractText Label="PATIENT(S)" NlmCategory="METHODS">Women (n = 49) with recurrent idiopathic miscarriages.</AbstractText><AbstractText Label="INTERVENTION(S)" NlmCategory="METHODS">In vitro fertilization with preimplantation genetic diagnosis for aneuploidy screening.</AbstractText><AbstractText Label="MAIN OUTCOME MEASURE(S)" NlmCategory="METHODS">Ongoing pregnancy rate (PR) and aneuploidy rate.</AbstractText><AbstractText Label="RESULT(S)" NlmCategory="RESULTS">The aneuploidy rate was, respectively, 43.85% and 66.95% in the younger and older group. The ongoing PR per cycle was 25.71% in the younger and 2.94% in the older patients.</AbstractText><AbstractText Label="CONCLUSION(S)" NlmCategory="CONCLUSIONS">There is no therapeutic evidence to prescribe IVF with or without preimplantation genetic diagnosis for aneuploidy screening for this heterogeneous group of patients.</AbstractText>
|
2,338,234 |
Molecular pathology of the CFTR locus in male infertility.
|
Congenital bilateral absence of the vas deferens (CBAVD) is a form of infertility with an autosomal recessive genetic background in otherwise healthy males. CBAVD is caused by cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations on both alleles in approximately 80% of cases. Striking CFTR genotypic differences are observed in cystic fibrosis (CF) and in CBAVD. The 5T allele is a CBAVD mutation with incomplete penetrance. Recent evidence confirmed that a second polymorphic locus exists and is a major CFTR modifier. The development of minigene models have led to results suggesting that CFTR exon 9 is skipped in humans because of unusual suboptimal 5' splice sites. An extremely rare T3 allele has been reported and it has recently been confirmed that the T3 allele dramatically increases exon 9 skipping and should be considered as a 'CF' mutation. Routine testing for the most prevalent mutations in the CF Caucasian population will miss most CFTR gene alterations, which can be detected only through exhaustive scanning of CFTR sequences. Finally, a higher than expected frequency of CFTR mutations and/or polymorphisms is now found in a growing number of monosymptomatic disorders, which creates a dilemma for setting nosologic boundaries between CF and diseases related to CFTR.
|
2,338,235 |
Benefits and challenges brought by improved results from in vitro fertilization.
|
Abstract In vitro fertilization (IVF), in which preimplantation-stage embryos are produced after ovarian stimulation and retrieval of preovulatory oocytes, now accounts for almost 2% of all births in Australia. For clinics performing in the top quartile of national results, the chance of a live birth for a woman under 35 years from one round of egg retrieval and IVF treatment is greater than 50%, albeit still with a greater than 20% risk of twins or higher order multiple pregnancy. Similar or better live birth rates are now obtainable with the elective transfer of a single embryo at the stage of blastocyst (5-6 days in culture), a policy that if adopted for younger women can reduce the risk of twins in a clinic to less than 15%. Current developments centre around improvements to embryo culture and the testing of embryos for chromosomal normality and other genetic and epigenetic variables before transfer, made possible by licences for embryo research protocols now being issued under the Commonwealth's Research Involving Human Embryos Act 2002.
|
2,338,236 |
Comparison of two screening methods for in-house genotyping in clinical pharmacology units.
|
Two genetic screening methods, the fluorescence resonance energy transfer (FRET) technique on the LightCycler and the real-time pyrophosphate detection technique on the Pyrosequencer have been compared with regard to their usefulness as screening methods for subject recruitment in clinical studies in pharmacology units. Two SNPs of possible clinical relevance were selected, namely the 118A>G SNP of the OPRM1 gene and the 3435C>T SNP of the ABCB1 gene. Genotypes diagnosed using conventional sequencing served as control. The allelic frequency of the mutated 118G allele of the OPRM1 gene was 12.7% and that of the mutated 3435T allele of the ABCB1 gene was 50.7%. All results obtained with the Pyrosequencer were in accord with those obtained using conventional sequencing. With the LightCycler, an incorrect genotype was assigned to 1 of the 130 DNA samples corresponding to an error rate of 0.8%. Although both methods were found suitable for rapid SNP detection, Pyrosequencing was the preferred method since it provides the nucleotide sequence directly thus facilitating interpretation.
|
2,338,237 |
Hyper-CK-emia as the sole manifestation of myotonic dystrophy type 2.
|
A 49-year-old man had an 8-year history of persistent, isolated elevation of serum creatine kinase (hyper-CK-emia) without muscle symptoms, and no electromyographic evidence of myotonia; his muscle biopsy showed features reminiscent of myotonic dystrophy (DM), with morphometric findings consistent with those described in DM type 2 (DM2). Genetic studies excluded mutations in the DM type 1 (DM1) gene, but revealed a CCTG repeat expansion in the ZNF9 gene, which is associated with DM2. Our data suggest that in asymptomatic patients with persistent hyper-CK-emia, DM2 should be considered in the differential diagnosis.
|
2,338,238 |
Molecular diagnosis of inheritable neuromuscular disorders. Part II: Application of genetic testing in neuromuscular disease.
|
Molecular genetic advances have led to refinements in the classification of inherited neuromuscular disease, and to methods of molecular testing useful for diagnosis and management of selected patients. Testing should be performed as targeted studies, sometimes sequentially, but not as wasteful panels of multiple genetic tests performed simultaneously. Accurate diagnosis through molecular testing is available for the vast majority of patients with inherited neuropathies, resulting from mutations in three genes (PMP22, MPZ, and GJB1); the most common types of muscular dystrophies (Duchenne and Becker, facioscapulohumeral, and myotonic dystrophies); the inherited motor neuron disorders (spinal muscular atrophy, Kennedy's disease, and SOD1 related amyotrophic lateral sclerosis); and many other neuromuscular disorders. The role of potential multiple genetic influences on the development of acquired neuromuscular diseases is an increasingly active area of research.
|
2,338,239 |
Analysis of promoter methylation in stool: a novel method for the detection of colorectal cancer.
|
<AbstractText Label="BACKGROUND & AIMS" NlmCategory="OBJECTIVE">Detection of tumor-derived DNA alterations in stool is an intriguing new approach with high potential for the noninvasive detection of colorectal cancer (CRC). Because of heterogeneity of tumors, usually multiple markers distributed throughout the human genome need to be analyzed. This is labor intensive and does not allow for high through-put screening. Therefore, markers with high sensitivity and good specificity are needed. We explored the potential of a single epigenetic marker in comparison with fecal occult blood testing (FOBT) for the discrimination of patients with CRCs and adenomas from those without.</AbstractText>Methylation-specific polymerase chain reaction (PCR) was performed to analyze hypermethylated in cancer 1 (HIC1) promoter methylation status in a blinded fashion in stool samples from 26 patients with CRC, 13 with adenoma > or =1 cm, 9 with hyperplastic polyps, 9 with chronic inflammatory bowel disease, and 32 with endoscopically normal colon.</AbstractText>Ninety-seven percent of the stool samples contained amplifiable DNA. Forty-two percent of the samples from patients with CRC and 31% of the samples from patients with colorectal adenoma > or =1 cm were positive for HIC1 promoter methylation. No methylated HIC1 promoter DNA was detected in the fecal DNA from patients with endoscopically normal colon or hyperplastic polyps.</AbstractText>The epigenetic marker HIC1 promoter methylation carries high potential for the remote detection of CRCs. We postulate that a panel of merely a few genetic and epigenetic markers will be required for the highly sensitive and specific detection of CRCs and adenomas in fecal samples from affected patients.</AbstractText>
|
2,338,240 |
Polymorphisms in the interleukin 17F gene (IL17F) and asthma.
|
Interleukin17F (IL17F) is a regulatory cytokine for T-cell-mediated immune responses. The gene coding for IL17F (IL17F) is located on chromosome 6p, a genomic region linked to asthma and asthma-related phenotypes in multiple genome scans. IL17F is expressed in lung tissue, in bronchoalveolar lavage fluid from asthmatic subjects, and in activated CD4+ cells. We were thus interested in testing for association between single-nucleotide polymorphisms (SNPs) and haplotypes in IL17F and asthma. To characterize polymorphisms in IL17F, we sequenced this gene in a group of African Americans and a group of European Americans. A total of 50 SNPs (30 not previously reported in a public database (dbSNP build 118)) and two insertions/deletions were detected in IL17F; five of these polymorphisms were genotyped in participants of the Nurses' Health Study. We then tested for association between SNPs and haplotypes in IL17F and physician-diagnosed asthma in subjects with (cases) and without (control subjects) physician-diagnosed asthma. None of the SNPs or haplotypes tested in IL17F were associated with asthma. The polymorphisms identified in this study may be used in future studies of association between IL17F and phenotypes related to immune responses.
|
2,338,241 |
Pediatric inflammatory bowel disease.
|
The prevalence of early-onset inflammatory bowel disease has been on the rise, with children and adolescents currently accounting for approximately 30% of all patients with this condition. Remarkable new advances in diagnostic modalities and therapy for adults with inflammatory bowel disease, and further information about the role of genetics in determining susceptibility to disease make the review of the recent literature in pediatric inflammatory bowel disease more timely than ever.</AbstractText>In the area of genetics, new studies provide strong evidence for genetic susceptibility to disease, and match genotype with phenotypic presentation. A few studies examine the use of noninvasive diagnostic modalities, such as MRI, and biomarkers (fecal lactoferrin) in pediatric inflammatory bowel disease. Remarkable new agents in therapy for adults with inflammatory bowel disease have been empirically administered to children with inflammatory bowel disease. The first attempts to systematically study the effects of these agents in children and adolescents are reviewed here. Furthermore, new studies revise our notion of surgical outcomes in pediatric inflammatory bowel disease.</AbstractText>Although premature for clinical practice application, the role of genetic testing in determining disease susceptibility and assisting with prognosis and course of therapy is clearly evolving and needs further study. As new therapeutic agents join the available treatments of inflammatory bowel disease it is imperative to include pediatric patients in clinical trials. The goals of future studies will be to alter the natural history of early-onset inflammatory bowel disease, reduce the frequency of recurrences, and perhaps reduce requirements for surgical intervention.</AbstractText>
|
2,338,242 |
Clinical management of hereditary colorectal cancer syndromes.
|
Colorectal cancer is the second leading cause of cancer-related death in the United States. Although most colorectal cancers are sporadic, approximately 25% have a familial predisposition, and 5 to 7% are hereditary and occur in genetically distinct high-risk families. This review focuses on four hereditary colon cancer syndromes: familial adenomatosus polyposis, hereditary nonpolyposis colorectal cancer, juvenile polyposis syndrome, and Peutz-Jeghers syndrome.</AbstractText>The management of the inherited colorectal cancer syndromes has progressed substantially over the past years because of advancement of genetic understanding and testing options, which have led to the possibility of preclinical diagnosis and early surveillance and treatment. Genetic testing is based on identification of specific abnormalities and should be combined with counseling of affected families.</AbstractText>Recent advances have contributed to the understanding of the molecular basis of various types of colorectal cancer, and among these, the inherited colorectal cancer syndromes have attracted much attention. Expanding recognition of clinical characteristics, targeted surveillance strategies and new methods of treatment have led to improved clinical management of these syndromes.</AbstractText>
|
2,338,243 |
Genetics of hypertension: lessons learnt from mendelian and polygenic syndromes.
|
This brief review discusses genetic and genomic aspects of hypertension. A special emphasis is given to currently available strategies for gene identifications, including studies of rare Mendelian hypertension, candidate gene evaluation, genome-wide scans and approaches based on the comparative genome analysis. We also discuss the growing potential for pharmacogenetic approaches and address briefly the issue of genetic testing in complex polygenic traits.
|
2,338,244 |
Mutagenic effects of 4-hydroxynonenal triacetate, a chemically protected form of the lipid peroxidation product 4-hydroxynonenal, as assayed in L5178Y/Tk+/- mouse lymphoma cells.
|
The lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) is cytotoxic and genotoxic at superphysiological concentrations. To characterize the mechanism of action of 4-HNE, we assessed genotoxic damage by 4-HNE and by 4-HNE triacetate [4-HNE(Ac)(3)] using the mouse lymphoma assay that measures the mutant frequency in the Tk gene. As a strong electrophile, 4-HNE reacts readily with nucleophilic centers on cellular components. When added extracellularly, it may react preferentially with proteins in culture medium or on the cell surface and not reach deeper cellular targets such as nuclear DNA. Therefore, 4-HNE(Ac)(3), a protected form of 4-HNE that is metabolically converted to 4-HNE in cells (Neely MD, Amarnath V, Weitlauf C, and Montine TJ, Chem Res Toxicol 15:40-47, 2002), was assayed in addition to 4-HNE. When added in serum-containing medium, 4-HNE was not mutagenic in the mouse lymphoma assay up to 38 muM (cytotoxicity = 13%). In contrast, exposure to 4-HNE(Ac)(3), which mimics intracellular formation of 4-HNE, resulted in dose-dependent induction of mutations. At 17 muM 4-HNE(Ac)(3) (cytotoxicity = 33%), the mutant frequency was 719 x 10(-6) (>7-fold higher than the spontaneous mutant frequency). Loss of heterozygosity analysis in the Tk mutants revealed that the majority of mutations induced by 4-HNE(Ac)(3) resulted from clastogenic events affecting a large segment of the chromosome. The results indicate that, in the presence of serum that approximates physiological conditions, 4-HNE generated intracellularly but not extracellularly is a strong mutagen via a clastogenic action at concentrations that may occur during oxidative stress.
|
2,338,245 |
[Antibiotic resistance--bacteria fight back].
|
Antibiotic resistance has become one of the leading problems in modern medicine. Resistance to antibiotics emerges in bacteria due to genetic mutations and consecutive selection of resistant mutants through selective pressure of antibiotics present in large amounts in soil, plants, animals and humans. Exchange of genetic material coding for resistance is possible even between unrelated organisms and further promotes the spread of resistance. Constantly evolving resistance mechanisms force experts to redefine breakpoint concentrations and interpretation of in vitro antibiotic sensitivity testing. Developing new antimicrobial agents does not seem to be enough to keep up pace with ever changing bacteria. Using antibiotics prudently and developing new approaches to the treatment of infections is vital for the future. The European Antimicrobial Resistance Surveillance System (EARSS) data clearly show that Scandinavian countries and The Netherlands have the lowest rates of resistance, while Southern and Eastern European countries have the highest prevalence of resistance. This is linked to the European Surveillance of Antimicrobial Consumption (ESAC) data that show very low consumption of antibiotics in Scandinavian countries and The Netherlands. Compliance with strict infection control policies related to multidrug resistant organisms is also high in these countries. Although it is important to be aware of the resistance problems worldwide, rational use of antibiotics should be based on the knowledge of local resistance patterns in common pathogens. Since 1996 there is a continuous surveillance of resistance in Croatia through the Croatian Committee for Antibiotic Resistance Surveillance. There is a particular concern about the rising penicillin and macrolide resistance in pneumococci. In Croatia, data for 2002 suggest that resistance to penicillin in pneumococci was 30% (low level) and 2% (high level). Among invasive isolates, 19% had reduced susceptibility to penicillin (< 1% high level resistance) as compared with 1% in The Netherlands and 53% in France. While methicillin-resistant Staphylococcus aureus (MRSA) has become endemic in many hospitals throughout the world, the most alarming event in 2002 was detection of Staphylococcus aureus fully resistant to vancomycin (VRSA). Of great concern is also reporting of MRSA community outbreaks in some parts of the world. Multiply resistant gram-negative pathogens, especially non-fermentative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumanii, have become dominant in many intensive care settings and some of these strains cannot be treated with any of the currently available systemic antibiotics. Raising awareness about the microbial resistance threat among health care workers and patients is essential if we are to preserve the efficacy of antibiotics for future generations.
|
2,338,246 |
Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns.
|
Mutations in the GJB2 (connexin 26, Cx26) gene are the major cause of nonsyndromic hearing impairment in many populations. Genetic testing offers opportunities to determine the cause of deafness and predict the course of hearing, enabling the prognostication of language development. In the current study, we compared severity of hearing impairment in 60 patients associated with biallelic GJB2 mutations and assessed the correlation of genotypes and phenotypes. Within a spectrum of GJB2 mutations found in the Japanese population, the phenotype of the most prevalent mutation, 235delC, was found to show more severe hearing impairment than that of V37I, which is the second most frequent mutation. The results of the present study, taken together with phenotypes caused by other types of mutations, support the general rule that phenotypes caused by the truncating GJB2 mutations are more severe than those caused by missense mutations. The present in vitro study further confirmed that differences in phenotypes could be explained by the protein expression pattern.
|
2,338,247 |
Genetic testing for hereditary nonpolyposis colorectal cancer.
|
Colorectal cancer remains a major cause of morbidity and mortality in United States. While most newly diagnosed cases are sporadic, a small percent of colorectal cancers are due to hereditary cancer syndromes, of which hereditary nonpolyposis colorectal cancer (HNPCC) is the most common. HNPCC is caused by mutations resulting in defective DNA mismatch repair gene function. Advances in molecular technology have enabled us to use genetic testing for HNPCC genes to identify high-risk families. Over the past several years, genetic testing for HNPCC has evolved from a research endeavor to a clinical test that often is an integral part of providing care for high-risk families. This article reviews the available genetic tests, genetic testing recommendations, interpretation of test results, and the clinical impact of genetic testing for HNPCC.
|
2,338,248 |
Phenotype determination guides swift genotyping of a DFNA2/KCNQ4 family with a hot spot mutation (W276S).
|
Genotype a family trait with autosomal dominant nonsyndromic sensorineural hearing impairment guided only by the phenotype.</AbstractText>Family study.</AbstractText>Tertiary referral center.</AbstractText>Fifteen family members.</AbstractText>In the first phase, sequence analysis was performed on DNA isolated from buccal swabs of the proband and her daughter, guided by the phenotype based on audiometric data that were already available. After detection of the W276S missense mutation in the KCNQ4 gene in both patients, this finding was confirmed in the other affected family members. All participants completed a questionnaire, were clinically examined, and underwent standard pure-tone audiometry. The results were analyzed to refine the phenotypic features of the family trait.</AbstractText>All clinically affected participants were carriers of the W276S hotspot mutation in exon 5 of the KCNQ4 gene on chromosome 1p34. Refined phenotypic features confirmed previously described phenotypes of DFNA2 families.</AbstractText>Phenotype determination can be cost saving and very effective in detecting the genotype of autosomal dominant nonsyndromic hearing impairment, especially when phenotype analyses can be performed on data that are already available or easily collected.</AbstractText>
|
2,338,249 |
A second-generation genome screen for linkage to type 1 diabetes in a Bedouin Arab family.
|
IDDM17 on chromosome 10 was identified in an initial genome screen of 13 members (10 affected) of a large Bedouin Arab family that had 19 relatives affected with type 1 diabetes. Two more children have now been diagnosed with the disease. A second genome screen with 45 members (17 affected members, spouses, and offspring; 382 markers) was performed. A parallel version of Genehunter was used for parametric and nonparametric linkage analyses. The nonparametric linkage analysis (NPL) confirmed the IDDM17 locus (NPL = 3.79; P = 0.001) with a prominent LOD (logarithm of the odds = 2.38) peak. These results demonstrate the strong potential of genetically homogenous, extended families for mapping genes that contribute to a complex disease.
|
2,338,250 |
Prevalence of diabetes-associated autoantibodies in schoolchildren: the Karlsburg Type 1 Diabetes Risk Study.
|
This study attempts to assess the prevalence of diabetes-associated autoantibodies in a general population in the northeastern part of Germany, with emphasis on autoantibodies against glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA-2A), and insulin (IAA) by radioassays >/= 98th percentile, and AAbs binding on pancreatic sections (ICA) by immunofluorescence >/= 10 Juvenile Diabetes Foundation units. From a total of 11,840 schoolchildren tested for all four AAbs, 821 (6.9%) children were positive for single AAbs, whereas 83 (0.7%) had multiple AAbs. If the primary screening were performed by testing GADA/IA-2A/IAA, 94% of probands with single AAbs and all with multiple AAbs would be identified. The combinations of GADA/IA-2A, GADA/IAA, and IA-2A/IAA would identify 97.6, 98.8, and 85.5% of probands with multiple AAbs, respectively. Thus, combined AAb screening in the general population identifies those probands at risk for diabetes.
|
2,338,251 |
Apolipoprotein E epsilon4 allele and lorazepam effects on memory in high-functioning older adults.
|
The apolipoprotein E (APOE) epsilon4 allele has been implicated as a significant risk factor in the development of late-onset Alzheimer disease, but the evidence of cognitive sequelae in healthy individuals has been mixed.</AbstractText>To determine if the APOE epsilon4 allele increases susceptibility to lorazepam-induced verbal learning impairment in nondemented older adults.</AbstractText>A placebo-controlled crossover design.</AbstractText>A community-based sample of subjects.</AbstractText>Sixty-four cognitively intact and highly educated (>12 years) adults. Twenty-four subjects (mean age, 66.3 years) were carriers of an APOE epsilon4 allele (epsilon4 positive) and 40 (mean age, 66.0 years) were not (epsilon4 negative).</AbstractText>All subjects received a single oral dose of placebo and lorazepam (0.5 and 1.0 mg) 1 week apart.</AbstractText>We used the Buschke Selective Reminding Test to assess verbal learning during a 5-hour period after placebo or lorazepam administration.</AbstractText>We found a time-related, dose-dependent effect of lorazepam, with long-term recall generally decreasing with higher doses of lorazepam at up to 2.5 hours. At 5 hours, the epsilon4-negative group showed significant improvement in long-term memory, but the epsilon4-positive group demonstrated a persistent deficit. Subsequent analysis revealed that the poor performance at 5 hours was found in an epsilon4-positive subgroup with lower baseline performance.</AbstractText>In cognitively intact, older adults, the effect of the APOE epsilon4 allele is not necessarily seen in the immediate response to benzodiazepine challenge. Rather, the APOE epsilon4 allele appears to affect the carrier's ability to recover from a cognitive challenge in a normal fashion, at least in a subgroup of subjects with relatively low baseline performance. This suggests that although carrying an APOE epsilon4 allele increases the risk for cognitive toxic effects, allele status alone is not a sufficient predictor of such effects. Studying the response to and the recovery from cognitive challenges may provide insights into the role of the APOE epsilon4 allele and its interaction with other factors in the development of Alzheimer disease and other age-related cognitive problems.</AbstractText>
|
2,338,252 |
Pyrosequencing-based approach for rapid detection of rifampin-resistant Mycobacterium tuberculosis.
|
Rifampin resistance in Mycobacterium tuberculosis could be determined within 2 h by using pyrosequencing-based approach. Pyrosequencing results of rifampin-resistant (n = 21) and rifampin-susceptible (n = 20) M. tuberculosis isolates were concordant with those based on drug susceptibility testing and conventional DNA sequencing. Results showed pyrosequencing-based approach is a rapid, sensitive, and efficient detection method of rifampin-resistant M. tuberculosis.
|
2,338,253 |
A rapid and simple method for detection of Asn363Ser polymorphism of the human glucocorticoid receptor gene.
|
Asn363Ser polymorphism of the human glucocorticoid receptor has been detected in approximately 4% of the population and it has been associated with several diseases and pathologic conditions. Here we describe a new, simple and cost-effective allele-specific PCR method for a rapid screening of this polymorphism. When compared to currently used PCR-based restriction fragment length polymorphism (RFLP) and direct DNA sequencing methods, the new allele-specific PCR method showed 100% accuracy for the detection of Asn363Asn and Asn363Ser genotypes. The feasibility of these methods were tested in 301 patients, including 47 patients with postmenopausal osteoporosis in whom the frequency of Asn363Ser polymorphism was similar to that found in control subjects (4.3% versus 4.4%).
|
2,338,254 |
Genetic risk estimation by healthcare professionals.<Pagination><StartPage>116</StartPage><EndPage>118</EndPage><MedlinePgn>116-8</MedlinePgn></Pagination><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">To assess whether healthcare professionals correctly incorporate the relevance of a favourable test outcome in a close relative when determining the level of risk for individuals at risk for Huntington's disease.</AbstractText><AbstractText Label="DESIGN AND SETTING" NlmCategory="METHODS">Survey of clinical geneticists and genetic counsellors from 12 centres of clinical genetics (United Kingdom, 6; The Netherlands, 4; Italy, 1; Australia, 1) in May-June 2002. Participants were asked to assess risk of specific individuals in 10 pedigrees, three of which required use of Bayes' theorem.</AbstractText><AbstractText Label="PARTICIPANTS" NlmCategory="METHODS">71 clinical geneticists and 41 other healthcare professionals involved in genetic counselling.</AbstractText><AbstractText Label="MAIN OUTCOME MEASURES" NlmCategory="METHODS">Proportion of respondents correctly assessing risk in the three target pedigrees; proportion of respondents who were confident of their estimate.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">50%-64% of respondents (for the three targets separately) did not include the favourable test information and incorrectly estimated the risks as being about equal to the prior risks; 77%-91% of these respondents were "sure" or "completely sure" that their estimations were correct. Twenty of the 112 respondents correctly estimated the risks for all three target pedigrees.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Clinical geneticists and genetic counsellors frequently use prior risks in situations where Bayes' theorem should be applied, leading to overestimations of the risk for an individual.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bonke</LastName><ForeName>Benno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Medical Psychology and Psychotherapy, Erasmus MC, Rotterdam, The Netherlands. [email protected]</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tibben</LastName><ForeName>Aad</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Lindhout</LastName><ForeName>Dick</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Clarke</LastName><ForeName>Angus J</ForeName><Initials>AJ</Initials></Author><Author ValidYN="Y"><LastName>Stijnen</LastName><ForeName>Theo</ForeName><Initials>T</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Australia</Country><MedlineTA>Med J Aust</MedlineTA><NlmUniqueID>0400714</NlmUniqueID><ISSNLinking>0025-729X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Med J Aust. 2005 Jun 6;182(11):596-7; author reply 597</RefSource><PMID Version="1">15938693</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D001315" MajorTopicYN="N">Australia</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001499" MajorTopicYN="N">Bayes Theorem</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002983" MajorTopicYN="N">Clinical Competence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D033142" MajorTopicYN="N">Genetic Services</DescriptorName><QualifierName UI="Q000706" MajorTopicYN="Y">statistics & numerical data</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005820" MajorTopicYN="N">Genetic Testing</DescriptorName><QualifierName UI="Q000706" MajorTopicYN="Y">statistics & numerical data</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006816" MajorTopicYN="N">Huntington Disease</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007558" MajorTopicYN="N">Italy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009426" MajorTopicYN="N">Netherlands</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010375" MajorTopicYN="N">Pedigree</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011338" MajorTopicYN="N">Probability Theory</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018570" MajorTopicYN="N">Risk Assessment</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName><QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006113" MajorTopicYN="N">United Kingdom</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2004</Year><Month>5</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2004</Year><Month>11</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2005</Year><Month>2</Month><Day>9</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2005</Year><Month>4</Month><Day>27</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2005</Year><Month>2</Month><Day>9</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">15698355</ArticleId><ArticleId IdType="doi">10.5694/j.1326-5377.2005.tb06610.x</ArticleId><ArticleId IdType="pii">bon10371_fm</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">15696853</PMID><DateCompleted><Year>2005</Year><Month>05</Month><Day>05</Day></DateCompleted><DateRevised><Year>2019</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0085-5928</ISSN><JournalIssue CitedMedium="Print"><Issue>241</Issue><PubDate><Year>2004</Year></PubDate></JournalIssue><Title>Scandinavian journal of gastroenterology. Supplement</Title><ISOAbbreviation>Scand J Gastroenterol Suppl</ISOAbbreviation></Journal>Hereditary non-polyposis colorectal cancer: identification of mutation carriers and assessing pathogenicity of mutations.
|
Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations in the mismatch repair (MMR) genes, which play an important role in maintaining genomic stability during DNA replication. Identification of MMR gene mutation carriers is important as this enables them to enrol in surveillance programmes, thus reducing their risk of cancer and increasing survival. Clinical criteria as well as non-clinical criteria have been formulated to select patients for mutation analysis. In this paper we review the approaches used to select patients for mutation analysis. Mutation analysis in the MMR genes may yield mutations of which the pathogenic nature is unclear. Criteria to determine the pathogenicity of such variants are discussed, as well as differences in design of functional assays to assess pathogenicity.
|
2,338,255 |
Testing adaptive plasticity to UV: costs and benefits of stem elongation and light-induced phenolics.
|
On exposure to ultraviolet radiation (UV), many plant species both reduce stem elongation and increase production of phenolic compounds that absorb in the UV region of the spectrum. To demonstrate that such developmental plasticity to UV is adaptive, it is necessary to show that the induced phenotype is both beneficial in inductive environments and maladaptive in non-inductive environments. We measured selection on stem elongation and phenolic content of seedlings of Impatiens capensis transplanted into ambient-UV and UV-removal treatments. We extended the range of phenotypes expressed, and thus the opportunity for selection in each UV treatment, by pretreating seedlings with either a low ratio of red:far-red wavelengths (R:FR), which induced stem elongation and reduced phenolic concentrations, or high R:FR, which had the opposite effect on these two phenotypic traits. Reduced stem length relative to biomass was advantageous for elongated plants under ambient UV, whereas increased elongation was favored in the UV-removal treatment. Selection favored an increase in the level of phenolics induced by UV in the ambient-UV treatment, but a decrease in phenolics in the absence of UV. These results are consistent with the hypotheses that reduced elongation and increased phenolic concentrations serve a UV-protective function and provide the first explicit demonstration in a wild species that plasticity of these traits to UV is adaptive. The observed cost to phenolics in the absence of UV may explain why many species plastically upregulate phenolic production when exposed to UV, rather than evolve constitutively high levels of these compounds. Finally, pretreatment with low R:FR simulating foliar shade did not exacerbate the fitness impact of UV exposure when plants had several weeks to acclimate to UV. This observation suggests that the evolution of adaptive shade avoidance responses to low R:FR in crowded stands will not be constrained by increased sensitivity to UV in elongated plants when they overtop their neighbors.
|
2,338,256 |
A mouse model of oral-esophageal carcinogenesis.
|
Squamous cancers of the oral cavity and esophagus are common worldwide. A number of environmental factors as well as genetic alterations have been identified. However, the specific combination of genetic events and their interplay with environmental carcinogens are largely un-known. Furthermore, no good animal model existed to study the molecular changes important in the induction and progression of the disease. Here we summarize the efforts made to establish a mouse model of oral-esophageal carcinogenesis. Cyclin D1 overexpressing(L2D1+) mice were generated using an EBV promoter to specifically target the oral cavity and the esophageal squamous epithelium. Besides analyzing different environmental factors, such as nitrosamines and zinc deficiency, cyclin D1 transgenic mice were crossbred with p53-deficient mice. While L2D1+ mice exhibited a phenotype of dysplasia, different combinations of mice result-ed in invasive oral-esophageal cancer. This mouse model provides a well-defined and reproducible model of oral-esophageal cancer that should be useful for testing chemopreventive, diagnostic, and therapeutic strategies.
|
2,338,257 |
[Screening and analysis of associated genes in the carcinogenesis and progression of gastric cancer].
|
To screen and analyze the important associated genes in different stages of gastric cancer.</AbstractText>Using suppression subtractive hybridization (SSH) to screen differentially expressed genes; detecting the expression of genes in different stages of gastric cancer with dot blot hybridization; and verifying the results with semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR).</AbstractText>Twenty-six differentially expressed gene fragments were obtained by means of SSH. Among them,24 were known genes, 1 was a new expressed sequence tags(EST), and 1 was a hypothetical gene. The results of dot blot hybridization demonstrated that the expressions of Annexin A2, RPS29, RPS12 etc. in dysplasia were higher than those in normal mucosa; the expressions of RPS12 etc.in early cancer were higher than those in normal mucosa;the expressions of cytochromosome C oxidase II, ferritin light chain, RPS12 etc. in advanced gastric cancer and lymph node metastases were consistently higher than those in normal mucosa. The expression of proteasome 26S subunit gene in advanced gastric cancer was higher than that in normal mucosa. The expression of RPS12 was consistently higher in different stages of gastric cancer. It was demonstrated by RT-PCR that the expression of RPS12 in gastric cancer was higher than that in normal mucosa.</AbstractText>The authors have identified some important genes that might be involved in the carcinogenesis and progression of gastric cancer, and RPS12 may play more important roles in gastric cancer.</AbstractText>
|
2,338,258 |
Association of defensin beta-1 gene polymorphisms with asthma.
|
Defensins are antimicrobial peptides that may take part in airway inflammation and hyperresponsiveness.</AbstractText>We characterized the genetic diversity in the defensin beta-1 (DEFB1) locus and tested for an association between common genetic variants and asthma diagnosis.</AbstractText>To identify single nucleotide polymorphisms (SNPs), we resequenced this gene in 23 self-defined European Americans and 24 African Americans. To test whether DEFB1 genetic variants are associated with asthma, we genotyped 4 haplotype-tag SNPs in 517 asthmatic and 519 control samples from the Nurses' Health Study (NHS) and performed a case-control association analysis. To replicate these findings, we evaluated the DEFB1 polymorphisms in a second cohort from the Childhood Asthma Management Program.</AbstractText>Within the NHS, single SNP testing suggested an association between asthma diagnosis and a 5' genomic SNP (g.-1816 T>C; P = .025) and intronic SNP (IVS+692 G>A; P = .054). A significant association between haplotype (Adenine, Cytosine, Thymine, Adenine [ACTA]) and asthma ( P = .024) was also identified. Associations between asthma diagnosis and both DEFB1 polymorphisms were observed in Childhood Asthma Management Program, a second cohort: g.-1816 T>C and IVS+692 G>A demonstrated significant transmission distortion ( P = .05 and .007, respectively). Transmission distortion was not observed in male subjects. The rare alleles (-1816C and +692A) were undertransmitted to offspring with asthma, suggesting a protective effect, contrary to the findings in the NHS cohort. Similar effects were evident at the haplotype level: ACTA was undertransmitted ( P = .04) and was more prominent in female subjects ( P = .007).</AbstractText>Variation in DEFB1 contributes to asthma diagnosis, with apparent gender-specific effects.</AbstractText>
|
2,338,259 |
Implementing prenatal screening for cystic fibrosis in routine obstetric practice.
|
The purpose of this study was to assess the outcome of the type of prescreening counseling on choices for prenatal cystic fibrosis screening.</AbstractText>From October 2001 to November 2002, regardless of ethnicity, all prenatal patients (n = 855) at the Air Force Medical Genetics Center, Biloxi, Miss, received education on prenatal screening for cystic fibrosis by group genetic counseling either by a presentation by a genetics professional (430 patients) or by a similar audiovisual presentation only (425 patients). A combination pretest/posttest document was used to evaluate learning and served as the consent. Partner testing was recommended for mutation-positive patients.</AbstractText>Fifty-eight percent patients requested screening, of whom 68% were white. Regardless of the type of counseling, patients showed an improvement in knowledge based on pre- and posttest scores. There was no significant difference in choices to undergo screening on the basis of counseling method. Fifteen mutation carriers were identified. Only 6 partners of mutation-positive patients were available and consented to be tested. To date, no infants have been born with cystic fibrosis.</AbstractText>Audio-visual counseling is an effective means to educate patients about genetic screening and does not require a trained genetics professional to administer. Partner testing in mobile populations may prove problematic.</AbstractText>
|
2,338,260 |
Sensitivity and specificity of the ViroSeq human immunodeficiency virus type 1 (HIV-1) genotyping system for detection of HIV-1 drug resistance mutations by use of an ABI PRISM 3100 genetic analyzer.
|
The ViroSeq human immunodeficiency virus type 1 (HIV-1) genotyping system is an integrated system for identification of drug resistance mutations in HIV-1 protease and reverse transcriptase (RT). Reagents are included for sample preparation, reverse transcription, PCR amplification, and sequencing. Software is provided to assemble and edit sequence data and to generate a drug resistance report. We determined the sensitivity and specificity of the ViroSeq system for mutation detection using an ABI PRISM 3100 genetic analyzer with a set of clinical samples and recombinant viruses. Twenty clinical plasma samples (viral loads, 1,800 to 10,500 copies/ml) were characterized by cloning and sequencing individual viral variants. Twelve recombinant-virus samples (viral loads, approximately 2,000 to 5,000 copies/ml) were also prepared. Eleven recombinant-virus samples contained drug resistance mutations as 40% mixtures. One recombinant-virus sample contained an insertion at codon 69 in RT (100% mutant). Plasma and recombinant-virus samples were analyzed using the ViroSeq system. Each sample was analyzed on three consecutive days at each of three testing laboratories. The sensitivity of mutation detection was 99.65% for the clinical plasma samples and 99.7% for the recombinant-virus preparations. The specificity of mutation detection was 99.95% for the clinical samples and 100% for the recombinant-virus mixtures. The base calling accuracy of the 3100 instrument was 99.91%. Mutations in clinical plasma samples and recombinant-virus samples were detected with high sensitivity and specificity, including mutations present as mixtures. This report supports the use of the ViroSeq system for identification of drug resistance mutations in HIV-1 protease and RT genes.
|
2,338,261 |
Use of the MicroSeq 500 16S rRNA gene-based sequencing for identification of bacterial isolates that commercial automated systems failed to identify correctly.
|
Reliable automated identification and susceptibility testing of clinically relevant bacteria is an essential routine for microbiology laboratories, thus improving patient care. Examples of automated identification systems include the Phoenix (Becton Dickinson) and the VITEK 2 (bioMerieux). However, more and more frequently, microbiologists must isolate "difficult" strains that automated systems often fail to identify. An alternative approach could be the genetic identification of isolates; this is based on 16S rRNA gene sequencing and analysis. The aim of the present study was to evaluate the possible use of MicroSeq 500 (Applera) for sequencing the 16S rRNA gene to identify isolates whose identification is unobtainable by conventional systems. We analyzed 83 "difficult" clinical isolates: 25 gram-positive and 58 gram-negative strains that were contemporaneously identified by both systems--VITEK 2 and Phoenix--while genetic identification was performed by using the MicroSeq 500 system. The results showed that phenotypic identifications by VITEK 2 and Phoenix were remarkably similar: 74% for gram-negative strains (43 of 58) and 80% for gram-positive strains were concordant by both systems and also concordant with genetic characterization. The exceptions were the 15 gram-negative and 9 gram-positive isolates whose phenotypic identifications were contrasting or inconclusive. For these, the use of MicroSeq 500 was fundamental to achieving species identification. In clinical microbiology the use of MicroSeq 500, particularly for strains with ambiguous biochemical profiles (including slow-growing strains), identifies strains more easily than do conventional systems. Moreover, MicroSeq 500 is easy to use and cost-effective, making it applicable also in the clinical laboratory.
|
2,338,262 |
Prenatal and newborn paternity testing with DNA analysis.
|
In rape against youthful girls which yields pregnancy after the abortion DNA examinations can be performed from the aborted foetal material to provide evidence of paternity of the suspect. In our present work we demonstrate six cases: four of them are rape cases and two where the mother abandoned her newborn baby. These cases proved that DNA-STR profiles can be determined from foetus after the abortion and perpetrator of a rape can be found. Due to our result we suggest that not only placenta but also bloody vernix caseosa is useful tissue for identifying the putative mother because vernix caseosa can be the carrier of the mother's blood.
|
2,338,263 |
Privacy protection for clinical and genomic data. The use of privacy-enhancing techniques in medicine.
|
Privacy includes the right of individuals and organisations to determine for themselves when, how and to what extent information about them is communicated to others. The growing need of managing large amounts of both clinical and genetic data raises important legal and ethical challenges. This paper introduces some of the privacy-protection problems related to classical and genomic medicine, and highlights the relevance of trusted third parties and of privacy-enhancing techniques (PETs) in the context of data collection, e.g., for research. Practical approaches based on two pseudonymisation models, for both batch data collection and interactive data storage, are presented. The actual application of the described techniques today proves the possible benefits for medicine that innovative privacy-enhancing techniques can provide. Technical PET solutions can unlock valuable data sources, otherwise not available.
|
2,338,264 |
Monoamine oxidases A and B gene polymorphisms in migraine patients.
|
Abnormal cortical activity and brainstem functioning are considered the possible etiopathogenetic factors of migraine. Monoamine oxidase A and B (MAO-A and -B) regulate the levels of monoamine neurotransmitters, so changes in their activity could participate in migraine pathogenesis. We have investigated the possible association of MAO-A and -B alleles and haplotypes with two common types of migraine, i.e. migraine without aura (MO) and migraine with aura (MA), on the sample of 110 migraineours (80 MO and 30 MA) and 150 controls. MAO-A promoter and MAO-B intron 13 polymorphisms were genotyped by the PCR-based methods. In addition, we have reevaluated the reported association between MAO-B intron 13 polymorphism and platelet MAO-B activity. The platelet MAO-B activity was determined fluorimetrically using kynuramine as a substrate. We have found a tendency toward association of the shorter variant of MAO-A gene promoter with migraine without aura in male subjects. Regarding investigated MAO-B polymorphism, no association with migraine or with platelet MAO-B activity was found. The suggestive association of the variant in MAO-A gene with migraine is considered worthy of independent replication. On the other hand, further studies on MAO-B polymorphism in migraine do not seem promising.
|
2,338,265 |
VH gene analysis of primary CNS lymphomas.
|
Primary CNS lymphomas (PCNSL) are highly malignant non-Hodgkin's lymphomas of B cell origin associated with a poor prognosis. These neoplasms show variable sensitivity to radio- and chemotherapy. A molecular basis for these differences in treatment responses has not yet been established for primary CNS lymphomas in a comprehensive series of patients. Here, we performed PCR analyses of the immunoglobulin (Ig) gene rearrangements of 18 PCNSL, including nine patients who responded well to therapy and nine patients who showed resistance to treatment. Variable gene segment distribution, mutation frequency of variable region genes, and clinical course were analyzed. Our data suggest a tendency towards a higher mean mutation frequency (17.2%) in patients responding to treatment and a lower mutation frequency (11.8%) in patients exhibiting a poor response to therapy, respectively. Furthermore, a restricted usage of the VH4 gene family was observed in the majority of nonresponding patients. To further validate the prognostic impact of these molecular parameters, studies in a larger cohort of patients will be required.
|
2,338,266 |
(GCG)11 founder mutation in the PABPN1 gene of OPMD Uruguayan families.
|
The dominant oculo-pharyngeal muscular dystrophy mutation consists of an expanded (GCN)(12-17) in the coding region of the PolyA Binding Protein Nuclear 1 gene. A founder effect has been demonstrated in Canadian and Bukhara Jewish populations with relatively high prevalence of this disease. Since the oculo-pharyngeal muscular dystrophy prevalence was remarkably high in Southern Uruguay, a founder effect was hypothesized. To identify the ancestral haplotype we determined the (GCN) repeat number and the variants of four intragenic SNPs in Uruguayan OPMD families and a control sample. All families carrying the mutation (GCG)(11)(GCA)(3)(GCG) shared a common ancestral haplotype and the age of the mutation was estimated in 37-53 generations by a composite likelihood method. One family carrying the (GCG)(9)(GCA)(3)(GCG) allele had a different haplotype. The genealogical and molecular data suggested that the common ancestors were Canary Islands' settlers that arrived in Uruguay in the XIX century.
|
2,338,267 |
Canine and feline models of human inherited muscle diseases.
|
Animal models are of immense importance for studying mechanisms of disease and testing new therapies, and rodents have been used extensively in the field of neuromuscular disorders. Mice and rats can be genetically manipulated to over-express or not express genes that are important to muscle function, and these animals can be available in large numbers for analysis. Other species, such as cats and dogs, cannot be manipulated in the same ways or be used in large numbers, but they have spontaneously occurring muscle diseases with clinical presentations more closely resembling those of the human disorders. Therefore, cats and dogs may become valuable as intermediate disease models. This review focuses on canine and feline models of human inherited muscle diseases with comparisons to rodent models and an emphasis on the muscular dystrophies.
|
2,338,268 |
Improving the referral process for familial breast cancer genetic counselling: findings of three randomised controlled trials of two interventions.
|
To evaluate the effectiveness and cost-effectiveness of two complementary interventions, using familial breast cancer as a model condition. The primary care intervention consisted of providing computerised referral guidelines and related education to GPs. The nurse counsellor intervention evaluated genetic nurses as substitutes for specialist geneticists in the initial assessment and management of referred patients.</AbstractText>The computerised referral guidelines study was a pragmatic, cluster randomised controlled trial (RCT) with general practices randomised to intervention or control groups. The nurse counsellor intervention was tested in two concurrent RCTs conducted in separate UK health service locations, using predetermined definitions of equivalence.</AbstractText>The computerised referral guidelines trial took place in general practices in Scotland from November 2000 to June 2001. The nurse counsellor intervention took place in a regional genetics clinic in Scotland, and in two health authorities in Wales served by a single genetics service during 2001.</AbstractText>The computerised referral guidelines study involved GPs and referred patients. Both nurse counsellor intervention trials included women referred for the first time, aged 18 years or over and whose main concern was family history of breast cancer.</AbstractText>The software system was developed with GPs, presenting cancer genetic referral guidelines in a checklist approach. Intervention GPs were invited to postgraduate update education sessions, and both intervention and control practices received paper-based guidelines. The intervention period was November 2000 to June 2001. For the nurse counsellor trial, trial 1 ran outpatient sessions with the same appointment length as the standard service offered by geneticists, but the nurse counsellor saw new patients at the first appointment and referred back to the GP or on to a clinical geneticist according to locally developed protocol, under the supervision of a consultant geneticist. The control intervention was the current service, which comprised an initial and a follow-up appointment with a clinical geneticist. In trial 2, a nurse counsellor ran outpatient sessions with the same appointment length as the new consultant-based cancer genetics service and new patients were seen at the first appointment and referred as in trial 1. The control intervention was a new service, and comprised collection of family history by telephone followed by a consultation with a clinical assistant or a specialist registrar, supervised by a consultant. The intervention was implemented between 1998 and 2001.</AbstractText>In the software system trial, the primary outcome was GPs' confidence in their management of patients with concerns about family history of breast cancer. For the nurse counsellor trial, the primary outcome was patient anxiety, measured using standard scales.</AbstractText>In the software system trial, 57 practices (230 GPs) were randomised to the intervention group and 29 (116 GPs) to the control group. No statistically significant differences were detected in GPs' confidence or any other outcomes. Fewer than half of the intervention GPs were aware of the software, and only 22 reported using it in practice. The estimated total cost was GBP3.12 per CD-ROM distributed (2001 prices). For the two arms of the nurse counsellor trial, 289 patients (193 intervention, 96 control) and 297 patients (197 intervention and 100 control) consented, were randomised, returned a baseline questionnaire and attended the clinic for trials 1 and 2 respectively. The analysis in both cases suggested equivalence in all anxiety scores, and no statistically significant differences were detected in other outcomes in either trial. A cost-minimisation analysis suggested that the cost per counselling episode was GBP10.23 lower in intervention arm than in the control arm and GBP10.89 higher in the intervention arm than in the control arm (2001 prices) for trials 1 and 2, respectively. Taking the trials together, the costs were sensitive to the grades of doctors and the time spent in consultant supervision of the nurse counsellor, but they were only slightly affected by the grade of nurse counsellor, the selected discount rate and the lifespan of equipment.</AbstractText>Computer-based systems in the primary care intervention cannot be recommended for widespread use without further evaluation and testing in real practice settings. Genetic nurse counsellors may be a cost-effective alternative to assessment by doctors. This trial does not provide definitive evidence that the general policy of employing genetics nurse counsellors is sound, as it was based on only three individuals. Future evaluations of computer-based decision support systems for primary care must first address their efficacy under ideal conditions, identify barriers to the use of such systems in practice, and provide evidence of the impact of the policy of such systems in routine practice. The nurse counsellor trial should be replicated in other settings to provide reassurance of the generalisability of the intervention and other models of nurse-based assessment, such as in outreach clinics, should be developed and evaluated. The design of future evaluations of professional substitution should also address issues such as the effect of different levels of training and experience of nurse counsellors, and learning effects.</AbstractText>
|
2,338,269 |
IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis.
|
The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.
|
2,338,270 |
Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection.
|
Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are "hypersensitive" to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed.
|
2,338,271 |
Leber's hereditary optic neuropathy--case report and literature review.
|
Leber's hereditary optic neuropathy is an important cause of progressive painless visual loss among young male patients.</AbstractText>To report on a case of a young patient with a clinical and neurophysiological condition suggestive of Leber's hereditary optic neuropathy, confirmed by genetic testing.</AbstractText>We describe a 17-year-old male with progressive bilateral visual loss. Two maternal uncles had had similar patterns of visual loss. The patient had a history of smoking and alcohol abuse. Neuro-ophthalmological examination revealed visual acuity of 20/800 in both eyes, with decreased direct and consensual pupillary light reflexes. Fundus examination demonstrated pale optic discs. The visual evoked potential test showed signs of conduction disturbances in both optic nerves and campimetric study showed complete visual loss in all fields of both eyes. A diagnosis of bilateral optic neuropathy with a clinical suspicion of Leber's hereditary optic neuropathy was made. A blood sample was submitted to genetic analysis in relation to the principal mutations of this disorder, and homoplasmic mutation in 11778 was detected, thereby confirming the diagnosis of Leber's hereditary optic neuropathy.</AbstractText>
|
2,338,272 |
Screening for CLCN5 mutation in renal calcium stone formers patients.
|
Thirty-five patients (23 males and 12 females), age 35 +/- 13 years old, presenting either idiopathic calcium nephrolithiasis, nephrocalcinosis or mild renal failure with idiopathic calcium nephrolithiasis were selected for the analysis of low molecular weight proteinuria and the possible mutations occurrence in the chloride channel gene CLCN5. The urinary ratio of beta2-microglobulin and creatinine (beta2M/Cr) was very high in a transplanted woman with nephrocalcinosis (> 3.23 mg/mmol) and slightly high in five patients (> 0.052 or < 1.0 mg/mmol) with multiple urological manipulations. Other studied patients showed beta2M/Cr ratio at normal range (0.003-0.052 mg/mmol) without gender difference (p > 0.05). Mutation analysis of CLCN5 gene was performed in 26 patients of 35 selected (11 with idiopathic hypercalciuria; 6 men with normal calciuria; 3 with mild renal insufficiency and 6 with nephrocalcinosis) and was normal in all subjects even in those with abnormal molecular weight proteinuria.</AbstractText>CLCN5 gene mutation is not a common cause of kidney stone disease or nephrocalcinosis in a group of Brazilian patients studied.</AbstractText>
|
2,338,273 |
Cost-effectiveness analysis of prenatal diagnosis: methodological issues and concerns.
|
With increasing concerns regarding rapidly expanding health care costs, cost-effectiveness analysis (CEA) provides a methodology to assess whether marginal gains from new technology are worth the increased costs. In the arena of prenatal diagnosis, particular methodological and ethical concerns include whether the effects of such testing on individuals other than the patient are included, how termination of pregnancy is included in the models, redundancy of screening and diagnostic methods, and how screening may reassure or cause anxiety in patients depending on their results. The existing literature has demonstrated cost-effectiveness of screening and diagnosis of neural tube defects, Down syndrome, and cystic fibrosis in the general population. Screening for genetic disorders which have a higher prevalence among particular groups has also been shown to be cost effective, including diseases such as hemoglobinopathies and Tay-Sachs disease. Understanding the methodology and salient issues of CEA is critical for researchers, editors and clinicians to accurately interpret results of the growing body of cost-effectiveness studies in prenatal diagnosis.
|
2,338,274 |
A community profile of alpha thalassaemia in Western Australia.
|
To investigate the current prevalence of alpha-thalassaemia in the population of Western Australia, which has received substantial immigration from South-East Asia during the last 30 years.</AbstractText>Over a 1-year period commencing July 2002, alpha-thalassaemia DNA testing was performed on 920 blood samples received from the Migrant Health Service, referring doctors or pathology laboratories in Western Australia. Molecular testing for alpha-thalassaemia was performed on extracted DNA for single and double alpha-globin gene deletions and mutations by PCR.</AbstractText>An alpha-globin gene abnormality was detected in 35.4% (326/920) of samples. There were 177 cases (50.6%) with a single gene deletion alpha(+)-thalassaemia, most commonly -3.7 kb, and 102 cases (31.2%) with double alpha-gene deletions (alpha(0)-thalassaemia), including 7 cases of HbH disease.</AbstractText>Overall, the findings amount to 1.7 new cases of alpha-thalassaemia per 10,000 population in the 12-month period and demonstrate that alpha-thalassaemia is an increasingly common disorder in the Western Australian population. This has important implications for community outreach programmes, genetic counselling and the screening of at-risk populations.</AbstractText>
|
2,338,275 |
Personal characteristics of older primary care patients who provide a buccal swab for apolipoprotein E testing and banking of genetic material: the spectrum study.
|
To determine the personal characteristics and reasons associated with providing a buccal swab for apolipoprotein E (APOE) genetic testing in a primary care study.</AbstractText>The study sample consisted of 342 adults aged 65 years and older recruited from primary care settings.</AbstractText>In all, 88% of patients agreed to provide a DNA sample for APOE genotyping and 78% of persons providing a sample agreed to banking of the DNA. Persons aged 80 years and older and African-Americans were less likely to participate in APOE genotyping. Concern about confidentiality was the most common reason for not wanting to provide a DNA sample or to have DNA banked.</AbstractText>We found stronger relationships between sociodemographic variables of age and ethnicity with participation in genetic testing than we did between level of educational attainment, gender, function, cognition, and affect.</AbstractText>
|
2,338,276 |
Short-term psychological impact of predictive testing for Machado-Joseph disease: depression and anxiety levels in individuals at risk from the Azores (Portugal).
|
The short-term impact of the pre-symptomatic genetic test (PT) for Machado-Joseph disease (MJD) in the Azores (Portuguese Islands) was assessed in 46 individuals at risk who completed the PT Program.</AbstractText>Scores for depression and anxiety were used as indicators of the subjects' emotional status immediately before the PT and 1 year after disclosure of the results.</AbstractText>Global levels of participation in the Azorean PT Program for MJD were high (20.7%), particularly in Flores Island (35.8%). For the total sample, mean scores of depression and anxiety before and after the PT presented without clinical significance. No differences were found for depression and anxiety scores before and after the PT. Furthermore, when grouped by test results (carriers/non-carriers), there were no differences between pre- and post-test levels.</AbstractText>Results indicate that the test result did not cause a decrease in the psychological well-being of the individuals tested. The high number of participants performing the PT in the small and isolated community of Flores Island, where MJD represents a source of stigma, was interpreted as an indication that in this particular population the PT offers the individuals at risk the possibility of liberating from a stigma, and, hence, from exclusion.</AbstractText>
|
2,338,277 |
Of biotechnology and man.
|
Lessons learned from the arena of other genetic 'resources' (such as plants and animals) together with the past decade of experience in human genetic research requires a rethinking of policy approaches. Whether at the level of whole populations, the family or the individual, the determination of rights and responsibilities is necessarily situated in the context of relationships. From an appreciation of these relationships emerge ethical principles that reflect the complexity of both the human person and new technologies. The elaboration of principles such as individuality, mutuality, reciprocity, solidarity, equity, citizenry and universality foster the possibility that traditional human rights and bioethic principles can be interpreted in a new way so as to promote and protect human well-being.
|
2,338,278 |
Methodological considerations in the study of genetic discrimination.
|
The potential significance and dimensions of genetic discrimination have been described extensively in published literature, but epidemiological and verified case data are limited. Obtaining unbiased data from individuals about discrimination which has been based on erroneous or unjustifiable assumptions about their genetic predispositions poses unique challenges. Through review and discussion of research literature, we identify methodological considerations for collecting valid epidemiological data on genetic discrimination from individuals in the community; in particular, we consider issues which relate to sampling, selection and response. We identify issues to promote sound study design, with particular attention to verification of genetic discrimination, and highlight the importance of clinical and genetic knowledge of complex genotype-phenotype relationships.
|
2,338,279 |
Estimating misclassification error with small samples via bootstrap cross-validation.
|
Estimation of misclassification error has received increasing attention in clinical diagnosis and bioinformatics studies, especially in small sample studies with microarray data. Current error estimation methods are not satisfactory because they either have large variability (such as leave-one-out cross-validation) or large bias (such as resubstitution and leave-one-out bootstrap). While small sample size remains one of the key features of costly clinical investigations or of microarray studies that have limited resources in funding, time and tissue materials, accurate and easy-to-implement error estimation methods for small samples are desirable and will be beneficial.</AbstractText>A bootstrap cross-validation method is studied. It achieves accurate error estimation through a simple procedure with bootstrap resampling and only costs computer CPU time. Simulation studies and applications to microarray data demonstrate that it performs consistently better than its competitors. This method possesses several attractive properties: (1) it is implemented through a simple procedure; (2) it performs well for small samples with sample size, as small as 16; (3) it is not restricted to any particular classification rules and thus applies to many parametric or non-parametric methods.</AbstractText>
|
2,338,280 |
Empirical Bayes screening of many p-values with applications to microarray studies.
|
Statistical tests for the detection of differentially expressed genes lead to a large collection of p-values one for each gene comparison. Without any further adjustment, these p-values may lead to a large number of false positives, simply because the number of genes to be tested is huge, which might mean wastage of laboratory resources. To account for multiple hypotheses, these p-values are typically adjusted using a single step method or a step-down method in order to achieve an overall control of the error rate (the so-called familywise error rate). In many applications, this may lead to an overly conservative strategy leading to too few genes being flagged.</AbstractText>In this paper we introduce a novel empirical Bayes screening (EBS) technique to inspect a large number of p-values in an effort to detect additional positive cases. In effect, each case borrows strength from an overall picture of the alternative hypotheses computed from all the p-values, while the entire procedure is calibrated by a step-down method so that the familywise error rate at the complete null hypothesis is still controlled. It is shown that the EBS has substantially higher sensitivity than the standard step-down approach for multiple comparison at the cost of a modest increase in the false discovery rate (FDR). The EBS procedure also compares favorably when compared with existing FDR control procedures for multiple testing. The EBS procedure is particularly useful in situations where it is important to identify all possible potentially positive cases which can be subjected to further confirmatory testing in order to eliminate the false positives. We illustrated this screening procedure using a data set on human colorectal cancer where we show that the EBS method detected additional genes related to colon cancer that were missed by other methods. This novel empirical Bayes procedure is advantageous over our earlier proposed empirical Bayes adjustments due to the following reasons: (i) it offers an automatic screening of the p-values the user may obtain from a univariate (i.e., gene by gene) analysis package making it extremely easy to use for a non-statistician, (ii) since it applies to the p-values, the tests do not have to be t-tests; in particular they could be F-tests which might arise in certain ANOVA formulations with expression data or even nonparametric tests, (iii) the empirical Bayes adjustment uses nonparametric function estimation techniques to estimate the marginal density of the transformed p-values rather than using a parametric model for the prior distribution and is therefore robust against model mis-specification.</AbstractText>R code for EBS is available from the authors upon request.</AbstractText>http://www.stat.uga.edu/~datta/EBS/supp.htm</AbstractText>
|
2,338,281 |
Array-based mutation detection of BRCA1 using direct probe/target hybridization.
|
We describe here an efficient microarray-based multiplex assay to detect Korean-specific mutations in breast cancer susceptibility gene BRCA1 using direct probe/target hybridization. Allele-specific oligonucleotides were covalently immobilized on an aldehyde-activated glass slide to prepare an oligonucleotide chip. From a wild-type sample, a two-step method was used to generate labeled multiplex polymerase chain reaction (PCR) amplification products of genomic regions containing the mutation sites. Amino allyl-dUTP, an amine-modified nucleotide, was incorporated during multiplex PCR amplifications and a monofunctional form of cyanine 3 dye was subsequently attached to the reactive amine group of the PCR products. Hybridization of the labeled PCR products to the oligonucleotide chip successfully identified all of the genotypes for the selected mutation sites. This work demonstrates that oligonucleotides chip-based analysis is a good candidate for efficient clinical testing for BRCA1 mutations when combined with the indirect strategy to prepare labeled target samples.
|
2,338,282 |
[Transcriptional abnormalities and genetic testing].
|
There is a rapidly growing literature on transcription abnormalities, e.g. differential expression of alleles and the role of some single nucleotide polymorphisms in altering splicing patterns. An average 10% of splicing mutations is reported in the Human Gene Mutation Database but this figure could climb to 50% for some genes such as NF1 or ATM. This paper therefore aims at clarifying some important aspects of transcriptional abnormalities in genetic testing. The main types of alterations are presented, i.e. exonic, intronic and promoter modifications that could modify or create consensus motif and/or secondary structures. DNA, RNA based-diagnostic strategies and in silico tools are then presented and their performances and limitations outlined to build up a picture of the current state of the art.
|
2,338,283 |
Are genetic self-tests dangerous? Assessing the commercialization of genetic testing in terms of personal autonomy.
|
Should a growing market for genetic self-tests be welcomed or feared? From the point of view of personal autonomy the increasing availability of predictive health information seems promising. Yet it is frequently pointed out that genetic information about future health may cause anxiety, distress and even loss of "life-hopes." In this article the argument that genetic self-tests undermine personal autonomy is assessed and criticized. I contend that opportunities for autonomous choice are not reduced by genetic information but by misperceptions and misunderstandings of the results of genetic tests. Since the interpretation of genetic information is sometimes distorted by the information provided about the genetic products, more attention should be given to deceitful marketing that overblows the utility of genetic products. Yet personal autonomy is reduced neither by genetic tests nor by genetic information and there is consequently no compelling case for the conclusion that genetic self-tests should be prohibited.
|
2,338,284 |
Concentrations of Escherichia coli and genetic diversity and antibiotic resistance profiling of Salmonella isolated from irrigation water, packing shed equipment, and fresh produce in Texas.
|
Fresh produce has been repeatedly implicated as a vehicle in the transmission of foodborne gastroenteritis. In an effort to assess the risk factors involved in the contamination of fresh produce with pathogenic bacteria, a total of 1,257 samples were collected from cantaloupe, oranges, and parsley (both in the field and after processing) and from the environment (i.e., irrigation water, soil, equipment, etc.). Samples were collected twice per season from two production farms per commodity and analyzed for the presence of Salmonella and Escherichia coli. E. coli was detected on all types of commodities (cantaloupe, oranges, and parsley), in irrigation water, and on equipment surfaces. A total of 25 Salmonella isolates were found: 16 from irrigation water, 6 from packing shed equipment, and 3 from washed cantaloupes. Salmonella was not detected on oranges or parsley. Serotyping, pulsed-field gel electrophoresis (PFGE), and repetitive element sequence-based PCR (rep-PCR) assays were applied to all Salmonella isolates to evaluate the genetic diversity of the isolates and to determine relationships between sources of contamination. Using PFGE, Salmonella isolates obtained from irrigation water and equipment were determined to be different from cantaloupe isolates; however, DNA fingerprinting did not conclusively define relationships between contamination sources. All Salmonella isolates were subjected to antimicrobial susceptibility testing using the disk diffusion method, and 20% (5 of 25) of the isolates had intermediate sensitivity to streptomycin. One Salmonella isolate from cantaloupe was resistant to streptomycin.
|
2,338,285 |
Genetic counseling for BRCA1/2: a randomized controlled trial of two strategies to facilitate the education and counseling process.
|
Due to the complexity of information surrounding BRCA1/2 counseling and testing and its time consuming nature, efforts to facilitate the genetic counseling and education process are needed. Using a 2 x 2 factorial design, two strategies were examined: a CD-ROM program for patients and a feedback checklist to the genetic counselor on patients' prior misconceptions. A total of 197 women attending a breast and ovarian cancer risk evaluation clinic for BRCA1/2 counseling were randomized into one of four conditions: standard care, CD-ROM only, feedback to counselor only, and both CD-ROM and feedback. Counseling outcomes included face-to-face time with the genetics team, knowledge acquisition, changes in worry about having a gene mutation, and genetic testing decisions. Overall, women who viewed the CD-ROM spent less time with the genetic counselor and were less likely to undergo genetic testing compared to women who did not view the CD-ROM. Feedback to the genetic counselor resulted in greater gains in knowledge of genetics and breast cancer. Among women less worried at baseline, those who viewed the CD-ROM showed no changes in worry following genetic counseling, in contrast to those who did not view the CD-ROM who increased in worry over time. This latter finding raises concerns about the impact of the increased worry on genetic testing decisions. No interaction effects of the two intervention arms were found. The study results support the importance of both strategies as valuable supplements to clinical BRCA1/2 counseling.
|
2,338,286 |
The diagnosis of adrenal insufficiency in a patient with Allgrove syndrome and a novel mutation in the ALADIN gene.
|
Allgrove syndrome is a genetic disorder inherited in an autosomal recessive pattern and characterized by a triad of adrenal insufficiency, achalasia, and alacrima. The gene affected by the mutation in patients with Allgrove syndrome is termed either AAAS or ALADIN (alacrima/achalasia/adrenal insufficiency/neurologic disorder). Adrenal insufficiency in patients with this disorder may develop as late as the third decade of life. We describe a 24-year-old female with Allgrove syndrome, in whom initial testing with 250 microg corticotropin (ACTH) stimulation test performed on 3 occasions produced normal serum cortisol values and results of the 1-microg ACTH stimulation tests performed on 6 occasions were conflicting. Insulin-induced hypoglycemia produced a nadir serum glucose value of 36 mg/dL without adequate serum cortisol stimulation, confirming presence of adrenal insufficiency. Gene sequencing identified 2 mutations in the triple A gene: an IVSC14 + 1 G to A mutation, which has been previously reported, and a novel R155P exon 6 mutation. We conclude that a novel R155P mutation in the ALADIN gene is associated with Allgrove syndrome and that insulin-induced hypoglycemia, rather than ACTH stimulation tests, should be used for accurate diagnosis of adrenal insufficiency in this disorder.
|
2,338,287 |
Endoscopic diagnosis and management of hereditary nonpolyposis colorectal cancer.
|
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition that accounts for 2 to 7% of all colorectal malignancies diagnosed annually. Endoscopic surveillance affords a rational strategy for reducing HNPCC-associated colorectal cancer incidence and mortality. The primary objective of this review is to highlight evidence supporting the role of endoscopy, particularly colonoscopy, in the preventive management of HNPCC. Clinical features, diagnostic criteria, and use of genetic testing to identify high-risk patients who warrant surveillance will also be discussed.</AbstractText>Colonoscopic surveillance has been shown to be an effective strategy for reducing HNPCC-associated colorectal cancer incidence and mortality. Current recommendations for the appropriate use of colonoscopic surveillance are based on an understanding of the natural history of the disease and the ability to identify high-risk individuals using both clinical criteria and genetic testing. High-risk individuals should undergo surveillance every 1 to 2 years beginning at age 20 years and then annually after age 40. Endoscopic surveillance is also recommended every 1 to 2 years following surgical resection of an HNPCC-associated cancer or adenoma because of the high rate of metachronous tumors.</AbstractText>Endoscopic surveillance remains the mainstay of preventive management of HNPCC. Appropriate use of genetic testing can aid in the identification of high-risk individuals and thereby optimize cost-effectiveness of this approach.</AbstractText>
|
2,338,288 |
Classification of BRCA1 missense variants of unknown clinical significance.
|
BRCA1 is a tumour suppressor with pleiotropic actions. Germline mutations in BRCA1 are responsible for a large proportion of breast-ovarian cancer families. Several missense variants have been identified throughout the gene but because of lack of information about their impact on the function of BRCA1, predictive testing is not always informative. Classification of missense variants into deleterious/high risk or neutral/low clinical significance is essential to identify individuals at risk.</AbstractText>To investigate a panel of missense variants.</AbstractText>The panel was investigated in a comprehensive framework that included (1) a functional assay based on transcription activation; (2) segregation analysis and a method of using incomplete pedigree data to calculate the odds of causality; (3) a method based on interspecific sequence variation. It was shown that the transcriptional activation assay could be used as a test to characterise mutations in the carboxy-terminus region of BRCA1 encompassing residues 1396-1863. Thirteen missense variants (H1402Y, L1407P, H1421Y, S1512I, M1628T, M1628V, T1685I, G1706A, T1720A, A1752P, G1788V, V1809F, and W1837R) were specifically investigated.</AbstractText>While individual classification schemes for BRCA1 alleles still present limitations, a combination of several methods provides a more powerful way of identifying variants that are causally linked to a high risk of breast and ovarian cancer. The framework presented here brings these variants nearer to clinical applicability.</AbstractText>
|
2,338,289 |
Milroy disease and the VEGFR-3 mutation phenotype.
|
Primary congenital lymphoedema (Milroy disease) is a rare autosomal dominant condition for which a major causative gene defect has recently been determined. Mutations in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene have now been described in 13 families world-wide. This is a review of the condition based on the clinical findings in 71 subjects from 10 families. All 71 individuals have a mutation in VEGFR-3. Ninety per cent of the 71 individuals carrying a VEGFR-3 mutation showed signs of oedema, which was confined in all cases to the lower limbs. In all but two cases onset of swelling was from birth. Other symptoms and signs included cellulitis (20%), large calibre leg veins (23%), papillomatosis (10%), and upslanting toenails (10%). In males, hydrocoele was the next most common finding after oedema (37%). Thorough clinical examination of these patients indicates that there are few clinical signs in addition to lower limb oedema. Rigorous phenotyping of patients produces a high yield of VEGFR-3 mutations.
|
2,338,290 |
[DNA-analysis in hereditary cancer: the importance of a reliable family history].
|
Three patients, a 45-year-old man, a 51-year-old woman and a 43-year-old woman, wanted to know whether they had a hereditary predisposition for cancer. The family of patient A fulfilled the clinical diagnostic criteria for hereditary non-polyposis colorectal carcinoma (HNPCC). The family of patient B fulfilled the clinical diagnostic criteria for hereditary breast/ovarian cancer (HBOC). The family of patient C did not completely fulfil the criteria for HBOC since only two family members had a confirmed diagnosis of breast cancer. In all three families, DNA-mutation analysis was performed. In families A and B no mutation was found. However, based on the family history, the diagnosis of hereditary cancer was made and recommendations for surveillance were given. After extensive counselling, one member of family B eventually decided to have prophylactic surgery performed. A few years later, a pathogenic mutation in BRCA2 was found in family B. In family C, an unclassified variant was found in BRCA1. Further investigations in the family were not possible, due to a lack of co-operation from family members. It is important to obtain a thorough and complete family history. When DNA-analysis remains inconclusive or if an unclassified variant is found, recommendations for surveillance will be based on this family history.
|
2,338,291 |
CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis.
|
Several reports demonstrate association between variants of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune diseases. CTLA-4 may generate autoimmunity by immune dysregulation, making CTLA-4 an attractive candidate gene for systemic lupus erythematosus (SLE) susceptibility. Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 14 independent studies (to July 2004) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at four polymorphic sites found in exon-1 (at +49), the promoter region (at -318 and -1722), and the 3' untranslated region (3'UTR) (dinucleotide repeat). We have evaluated both fixed and random effect models, depending on the presence of between-study heterogeneity. The data demonstrate that the exon-1 +49 polymorphism is significantly associated with SLE susceptibility. The overall risk, measured by odds ratio (OR), for exon-1 +49 GG genotype is 1.287 [95% confidence interval (CI)=1.031-1.562, P=0.011]. Stratification by ethnicity indicates the exon-1 +49 GG genotype is associated with SLE, at least in Asians (OR=1.293, 95% CI=1.031-1.620, P=0.026). European-derived populations have an effect of similar magnitude (OR=1.268, 95% CI=0.860-1.870, P=0.230), though not significant. Similar trends are found in allele-specific risk estimates and disease association. The OR for the exon-1 +49 risk allele (G) in Asians is 1.246 (95% CI=1.057-1.469, P=0.009), while Europeans have no evidence of allelic association (OR=0.978, 95% CI=0.833-1.148, P=0.780). In conclusion, this meta-analysis supports the CTLA-4 exon-1 +49 (A/G) polymorphism influencing the risk for developing SLE, especially in Asians.
|
2,338,292 |
Perspectives on use and protection of genetic information in work settings: results of a preliminary study.
|
The societal use of genetic information raises ethical concerns, and the views of working persons regarding genetic information have received little attention. We performed an empirical project to characterize perspectives of 63 employees at two sites who expressed strong interest in learning about and protecting their personal genetic information. Genetic data were seen as more sensitive than other health data, and disclosure of genetic susceptibility was perceived as having negative consequences. This study suggests the value of exploring the perspectives of key stakeholders most directly affected by genetic applications across diverse societal settings.
|
2,338,293 |
The genetics of hearing loss.
|
Hearing impairment is the most common sensory deficit with half of the causes of hearing loss having a genetic basis. There is a range of treatment devices but these do not correct the underlying pathology. Advances in molecular biology have greatly enhanced our understanding of the pathophysiology of genetic hearing loss, including potential treatments.
|
2,338,294 |
Evidence for the gamma-amino-butyric acid type B receptor 1 (GABBR1) gene as a susceptibility factor in obsessive-compulsive disorder.
|
Obsessive-compulsive disorder (OCD) is a well-recognized severe neuropsychiatric illness. Genetic factors are believed to be important etiologically. Although historically genetic testing has focused on the serotonergic and dopaminergic systems, there is increasing evidence that the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), may also be functionally involved. Furthermore the GABA type B receptor 1 (GABBR1) gene has been localized to chromosome 6p21.3 region, which has shown linkage to OCD. We investigated five polymorphisms (A-7265G substitution; C10497G substitution; A33795G substitution in the 3'-UTR; Ser-491-Ser-T1473C transition; Phe-659-Phe-T1977C transition) in the GABBR1 gene in a sample of 159 DSM-IV OCD probands and their families, using the transmission disequilibrium test (TDT). A trend was observed with an over-transmission of -7265A allele at the A-7265G polymorphism and OCD (chi2 = 3.270, P = 0.071). Moreover, the TDT haplotype analysis using TRANSMIT showed a trend toward association with the haplotype of the five polymorphisms together [2.1.1.2.1 (A-7265G.C10497G.Ser-491-Ser.Phe-659-Phe.A33795G)] with a Chi-square value of 3.418, which corresponds to a P-value of 0.065 (overall chi2 = 6.353, 5 df, P = 0.273). Moreover, a trend was observed for the total Yale-Brown obsessive-compulsive scale score in the A-7265G polymorphism (-7265A: z = 1.934, P = 0.053) using the Family-Based Association Test, considering the diagnosis of OCD and then the clinically relevant quantitative phenotypes. The observed trends suggest that further investigations of the role of the GABBR1 gene in OCD are warranted.
|
2,338,295 |
Linkage to peroxisome proliferator-activated receptor-gamma in SAMP1/YitFc mice and in human Crohn's disease.
|
Genetic predisposition is implicated strongly in Crohn's disease. Disease-associated mutations in NOD2/CARD15 , the best-studied susceptibility gene in this disorder, explain only a small fraction of the heritability. The SAMP1/YitFc (SAMP1/Fc) mouse strain expresses many features of Crohn's disease in humans. We bred SAMP1/Fc to disease-resistant AKR mice to identify additional susceptibility genes that may play a role in human disease.</AbstractText>Linkage disequilibrium mapping was performed in an (AKR x SAMP1/Fc) backcross to SAMP1/Fc, followed by sequencing, expression analysis using reverse transcription polymerase chain reaction (PCR) and immunohistochemistry, and functional testing in vivo of the regional candidate gene encoding the peroxisome proliferator-activated receptor gamma ( Pparg ). A cohort-based association study was performed in humans.</AbstractText>We show that ileitis is blocked in SAMP1/Fc mice by inheritance of AKR alleles on chromosome 6 in the region of Pparg . Major differences in Ppargamma expression in the parental mouse strains are found specifically in the crypts of the small intestine, and treatment of ileitis-prone mice with a Ppargamma agonist decreased disease severity in susceptible mice expressing low levels of the protein. Rare alleles of PPARG are associated significantly with Crohn's disease in humans.</AbstractText>We have identified Pparg as a susceptibility gene in both the SAMP/Yit mouse and in human Crohn's disease. Similarities between Crohn's disease and the SAMP1/Fc model suggest that the effect of this gene in humans may be mediated through regulation of PPARgamma activity in the crypts of the small intestine.</AbstractText>
|
2,338,296 |
A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease.
|
Previously, we identified 2 functionally relevant polymorphisms in the SLC22A4 / 22A5 genes at the IBD5 locus that alter gene/protein function and comprise a 2-allele haplotype ( SLC22A -TC) associated with increased risk for Crohn's disease (CD). Here we examine the contribution of this susceptibility haplotype alone and in combination with CARD15 variants to CD subphenotypes and to susceptibility to ulcerative colitis (UC).</AbstractText>Phenotype-genotype associations were evaluated in a Canadian cohort including 507 patients with CD, 216 patients with UC, and 352 ethnically matched controls genotyped for SLC22A4 C1672T, SLC22A5 G-207C, and the major CD-associated CARD15 variants.</AbstractText>The SLC22A -TC haplotype was strongly associated ( P < .0001) with CD in the non-Jewish subgroup of this cohort, and the combination of SLC22A -TC homozygosity and one or more of the common CARD15 disease susceptibility alleles engendered a 7.5-fold increase in risk for CD ( P = 9 x 10 -8 ) and a 4.5-fold increase in risk for ileal disease ( P = .001). The risk haplotype showed only a suggestive association with CD in the Jewish subgroup and no association with UC in the cohort or in subgroups stratified by CARD15 genotypes.</AbstractText>The SLC22A -TC haplotype acts together with CARD15 disease susceptibility alleles to increase risk for CD and ileal disease among CD patients but does not contribute to risk for UC in this Canadian cohort. The association of the SLC22A -TC haplotype and CARD15 alleles with ileal disease suggests that these variants have biologically intertwined effects in the pathogenesis of CD.</AbstractText>
|
2,338,297 |
Bone loss induced by ovariectomy in rats is prevented by gene transfer of parathyroid hormone or an Arg-Gly-Asp-containing peptide.
|
Osteoporosis is a major and growing healthcare concern as the population ages. The genes of both a Arg-Gly-Asp (RGD)-containing peptide and parathyroid hormone (PTH) were used to reduce bone loss induced by ovariectomy (OVX) in rats. Plasmids with either RGD or PTH gene were delivered into the quadriceps of OVX rats. The expression of the genes was detected by RT-PCR and radioimmunoassay. Analysis of bone mineral density, bone mechanical testing and bone mineral content indicated an improvement in bone properties in both RGD-transferred and PTH-transferred rats compared to OVX rats. Gene transfer of either RGD or PTH is therefore a possible approach to prevent bone loss in OVX rats thus providing a potential method to prevent osteoporosis in clinical situations.
|
2,338,298 |
A note on appropriate use of statistical tests of mutation rates from ordered groups.
|
Recently it was found that the frequency of familial dysautonomia (FD) carriers in Ashkenazi Jews (AJ) was higher in AJ of Polish descent compared to AJ of non-Polish descent. The study population was classified into groups ranging from no to full Polish origin. The statistical procedure used to compare the frequencies of FD carriers did not incorporate this intrinsic ordering of individuals by degree of Polish ancestry. In this paper we describe a test designed to utilize this information and show that it is more powerful than the standard test of equality of proportions. In particular, the p value of the trend test on their data is noticeably lower (0.003) than 0.012 found by the standard test, providing stronger evidence for a relationship between allele frequency and Polish descent.
|
2,338,299 |
Preconceptional cystic fibrosis carrier screening: opinions of general practitioners, gynecologists, and pediatricians in the Netherlands.
|
Knowledge of the opinions of physicians with regard to preconceptional cystic fibrosis (CF) carrier screening and the possible factors that are associated with their opinions is important for the implementation of such a screening program. Data were obtained from a study in which genetic knowledge, opinions with regard to genetic testing and related skills were investigated. A questionnaire, developed and used by American researchers, was adapted to the Dutch health care situation, and sent to randomly selected general practitioners (GPs) (n = 200), gynecologists (GYNs) (n = 300), and pediatricians (PEDs) (n = 265). In this part of the study, their opinions with regard to genetic preconceptional CF carrier screening in different situations were assessed. The response rate for the GPs, GYNs, and PEDs was 64%, 69%, and 72%, respectively. In total, 63% of the GPs, 69% of the GYNs and 72% of the PEDs supported preconceptional CF carrier testing if a couple requested a test. Sixteen percent, 19% and 25%, respectively, were in favor of actively offering a test with 95% test sensitivity to all couples who were planning a pregnancy. A positive opinion on preconceptional CF carrier screening was associated with the following variables: "considering the test sensitivity as less important" (GPs, GYNs), "high perceived risk of having a child with CF" (GYNs), "providing genetic counselling in their own practice" (PEDs) and "reassurance when both partners test negative" (PEDs). Physicians are sympathetic toward preconceptional CF carrier screening if the couples themselves request a test. Physicians had reservations about routinely offering a CF carrier test.
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.