125 research outputs found
ALFRED: an allele frequency resource for research and teaching
ALFRED (http://alfred.med.yale.edu) is a free, web accessible, curated compilation of allele frequency data on DNA sequence polymorphisms in anthropologically defined human populations. Currently, ALFRED has allele frequency tables on over 663 400 polymorphic sites; 170 of them have frequency tables for more than 100 different population samples. In ALFRED, a population may have multiple samples with each ‘sample’ consisting of many individuals on which an allele frequency is based. There are 3566 population samples from 710 different populations with allele frequency tables on at least one polymorphism. Fifty of those population samples have allele frequency data for over 650 000 polymorphisms. Records also have active links to relevant resources (dbSNP, PharmGKB, OMIM, Ethnologue, etc.). The flexible search options and data display and download capabilities available through the web interface allow easy access to the large quantity of high-quality data in ALFRED
One Large Kindred Excludes a Locus for Multiple Endocrine Neoplasia Type 2A from about 25% of the Human Autosomal Genetic Map
This report presents pairwise linkage results from our search for the locus of the gene (MEN2A) for the multiple endocrine neoplasia type 2A (MEN-2A) syndrome in one large kindred (the N kindred), clearly segregating for an autosomal dominant form. About 25% of the autosomal genome is excluded when these new results are combined with those we have published previously. The genetic markers employed are distributed across at least 19 of the 22 autosomes. Seven genetic markers whose chromosomal locations are not yet established have also been studied
Routes for breaching and protecting genetic privacy
We are entering the era of ubiquitous genetic information for research,
clinical care, and personal curiosity. Sharing these datasets is vital for
rapid progress in understanding the genetic basis of human diseases. However,
one growing concern is the ability to protect the genetic privacy of the data
originators. Here, we technically map threats to genetic privacy and discuss
potential mitigation strategies for privacy-preserving dissemination of genetic
data.Comment: Draft for comment
Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope
Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in
immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant
to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about
appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive
diagnostic workup and even more for new, effective antifungal drugs to improve
patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp.
and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScopeVR
registry. For 208 Scedosporium spp. infections solid organ transplantation (n¼58, 27.9%) and for
56 L. prolificans infection underlying malignancy (n¼28, 50.0%) were the most prevalent risk factors.
L. prolificans infections frequently presented as fungemia (n¼26, 46.4% versus n¼12, 5.8%
for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome
for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better
overall outcome in both groups compared to treatment with amphotericin B formulations. This
review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and
investigational antifungals, and treatment strategies of severe infections caused by Scedosporium
spp. and L. prolificans
Short tandem repeat profiling: part of an overall strategy for reducing the frequency of cell misidentification
The role of cell authentication in biomedical science has received considerable attention, especially within the past decade. This quality control attribute is now beginning to be given the emphasis it deserves by granting agencies and by scientific journals. Short tandem repeat (STR) profiling, one of a few DNA profiling technologies now available, is being proposed for routine identification (authentication) of human cell lines, stem cells, and tissues. The advantage of this technique over methods such as isoenzyme analysis, karyotyping, human leukocyte antigen typing, etc., is that STR profiling can establish identity to the individual level, provided that the appropriate number and types of loci are evaluated. To best employ this technology, a standardized protocol and a data-driven, quality-controlled, and publically searchable database will be necessary. This public STR database (currently under development) will enable investigators to rapidly authenticate human-based cultures to the individual from whom the cells were sourced. Use of similar approaches for non-human animal cells will require developing other suitable loci sets. While implementing STR analysis on a more routine basis should significantly reduce the frequency of cell misidentification, additional technologies may be needed as part of an overall authentication paradigm. For instance, isoenzyme analysis, PCR-based DNA amplification, and sequence-based barcoding methods enable rapid confirmation of a cell line’s species of origin while screening against cross-contaminations, especially when the cells present are not recognized by the species-specific STR method. Karyotyping may also be needed as a supporting tool during establishment of an STR database. Finally, good cell culture practices must always remain a major component of any effort to reduce the frequency of cell misidentification
Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope
Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in
immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant
to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about
appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive
diagnostic workup and even more for new, effective antifungal drugs to improve
patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp.
and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScopeVR
registry. For 208 Scedosporium spp. infections solid organ transplantation (n¼58, 27.9%) and for
56 L. prolificans infection underlying malignancy (n¼28, 50.0%) were the most prevalent risk factors.
L. prolificans infections frequently presented as fungemia (n¼26, 46.4% versus n¼12, 5.8%
for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome
for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better
overall outcome in both groups compared to treatment with amphotericin B formulations. This
review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved
and investigational antifungals, and treatment strategies of severe infections caused by Scedosporium spp. and L. prolificansWe thank Sabine Wrackmeyer for her private donation to
support the projec
SNP array profiling of mouse cell lines identifies their strains of origin and reveals cross-contamination and widespread aneuploidy
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Genome-wide association study of Tourette Syndrome
Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder
Ethnic Related Selection for an ADH Class I Variant within East Asia
The alcohol dehydrogenases (ADH) are widely studied enzymes and the evolution of the mammalian gene cluster encoding these enzymes is also well studied. Previous studies have shown that the ADH1B*47His allele at one of the seven genes in humans is associated with a decrease in the risk of alcoholism and the core molecular region with this allele has been selected for in some East Asian populations. As the frequency of ADH1B*47His is highest in East Asia, and very low in most of the rest of the world, we have undertaken more detailed investigation in this geographic region.Here we report new data on 30 SNPs in the ADH7 and Class I ADH region in samples of 24 populations from China and Laos. These populations cover a wide geographic region and diverse ethnicities. Combined with our previously published East Asian data for these SNPs in 8 populations, we have typed populations from all of the 6 major linguistic phyla (Altaic including Korean-Japanese and inland Altaic, Sino-Tibetan, Hmong-Mien, Austro-Asiatic, Daic, and Austronesian). The ADH1B genotyping data are strongly related to ethnicity. Only some eastern ethnic phyla or subphyla (Korean-Japanese, Han Chinese, Hmong-Mien, Daic, and Austronesian) have a high frequency of ADH1B*47His. ADH1B haplotype data clustered the populations into linguistic subphyla, and divided the subphyla into eastern and western parts. In the Hmong-Mien and Altaic populations, the extended haplotype homozygosity (EHH) and relative EHH (REHH) tests for the ADH1B core were consistent with selection for the haplotype with derived SNP alleles. In the other ethnic phyla, the core showed only a weak signal of selection at best.The selection distribution is more significantly correlated with the frequency of the derived ADH1B regulatory region polymorphism than the derived amino-acid altering allele ADH1B*47His. Thus, the real focus of selection may be the regulatory region. The obvious ethnicity-related distributions of ADH1B diversities suggest the existence of some culture-related selective forces that have acted on the ADH1B region
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