Project description:In conditions of nitrogen limitation, Saccharomyces cerevisiae strains differ in their fermentation capacities, due to differences in their nitrogen requirements. A population of 133 individuals from the F2 segregant population from a cross between two strains with different nitrogen requirements for efficient fermentation has been analyzed for their fermentation capacities. Two groups of 15 strains were defined, one group of High and one of Low Nitrogen requirement. These two groups are compared in order to detect genomic regions involved in the differences of nitrogen requirement. We used a custom isothermal array that has been designed for the detection of SNP at 6317 position on RM11.1a genome sequence http://www.broadinstitute.org/annotation/genome/saccharomyces_cerevisiae.3/Home.html) and obtained from the comparison with the genome sequence of strain Saccharomyces P3-D5.
Project description:Background: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. Objectives: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. Results: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst=0.036, CHB: Fst=0.031, CHS: Fst=0.027, CDX: Fst=0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p =1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)).
Project description:In our genome-wide association study, we searched for an association of genetic variants with colorectal cancer, type 1 diabetes, Hodgkin lymphoma and Diffuse large B-cell lymphoma among Polish population.
Project description:We use targeted bisulfite PCR and next-generation 454 sequencing of multiple amplicons to analyze the association of cis-regulated allele-specific methylation (ASM) with multiple complex disease-associated variants in a population of 82 individuals. We detect ASM at four variants implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn’s disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). 82 samples analysed
Project description:In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip Human Exon 1.0 ST Array. A variety of biological processes such as immune response and mRNA metabolic process were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations. Exon level expression on 176 HapMap cell lines.
Project description:In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip Human Exon 1.0 ST Array. A variety of biological processes such as immune response and mRNA metabolic process were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations.
Project description:Pseudoexfoliation syndrome (PEXS) is a late-onset disorder in which fibrillar material accumulates at abnormally high concentrations mainly in the anterior segment of the eye. PEXS is the most common cause of secondary glaucoma, which can ultimately lead to blindness and is associated with a higher risk of cataract and serious complications following different types of intraocular surgery. Although PEXS clearly has a genetic component, it remains poorly explored. In our genome-wide association study, we searched for an association of genetic variants with this disorder among older Poles with PEXS without glaucoma.
Project description:Histone modifications are important markers of function and chromatin state, yet the DNA elements that direct them to specific locations in the genome are poorly understood. Here we use the genetic variation in Yoruba lymphoblastoid cell lines as a natural experiment to identify genetic differences that affect histone marks and to better understand their relationship with transcriptional regulation. Across the genome, we identified hundreds of quantitative trait loci that impact histone modification or RNA polymerase (PolII) occupancy. In many cases the same variant is associated with quantitative changes in multiple histone marks and PolII, as well as in DNaseI sensitivity and nucleosome positioning, indicating that these molecular phenotypes often share a single underlying genetic cause. Variants that impact chromatin at distal regulatory sites frequently also direct changes in chromatin and gene expression at associated promoters; while most of these distal regulators enhance promoter activity, some act as distal chromatin silencers. Finally, we find that polymorphisms in transcription factor binding sites are often causally responsible for variation in local histone modification. In summary, the class of variants identified here generate coordinated changes in chromatin both locally and sometimes at distant locations, frequently drive changes in gene expression, and likely play an important role in the genetics of complex traits. ChIP-seq of RNA Polymerase II and 4 histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3) in 10 unrelated Yoruba HapMap lymphoblastoid cell lines
Project description:Transfer RNAs (tRNAs) play an essential role in protein synthesis by linking the nucleic acid sequences of gene products to the amino acid sequences of proteins. Although only 32 tRNAs are needed to decode all 61 sense codons in the genetic code, there are > 400 functional tRNA genes in the humans. Adding to this diversity, there are many single nucleotide polymorphisms in tRNAs across our population, including anticodon variants that mistranslate the genetic code. In human genomes, we identified three alanine tRNA (tRNAAla) variants with non-synonymous anticodon mutations: tRNAAlaCGC G35T, tRNAAlaUGC G35A, and tRNAAlaAGC C36T. Since alanyl-tRNA synthetase (AlaRS) does not recognize the anticodon, we hypothesized that these human tRNAAla variants will mis-incorporate Ala at glutamate (Glu), valine (Val), and threonine (Thr) codons. We found that human cells expressing the naturally occurring tRNAAla variants were characterized by defects in protein production and cell growth. Using mass spectrometry, we confirmed and estimated Ala mis-incorporation levels at Glu (0.7%), Val (5%) and Thr (0.1%) codons. Although Ala mis-incorporation was higher at Val codons, cells mis-incorporating Ala at Glu codons had the most severe defect in protein production. Significant growth defects were observed in cells mistranslating Glu and Val codons, while the low level of mis-incorporation at Thr codons was well-tolerated in human cells. The data demonstrate the ability of natural human tRNAAla variants to generate mistranslation leading to a phenotypic response that depends on the nature of the amino acid replacement and the level of mis-incorporation.