Disease-associated variants in different categories of disease located in distinct regulatory elements

作者: Meng Ma , Ying Ru , Ling-Shiang Chuang , Nai-Yun Hsu , Li-Song Shi

DOI: 10.1186/1471-2164-16-S8-S3

关键词: GermlineBiologyDNA microarrayHuman genomePromoterGenetic variationGeneticsGenome-wide association studyFunctional genomicsRegulatory sequence

摘要: The invention of high throughput sequencing technologies has led to the discoveries hundreds thousands genetic variants associated with human diseases. Many these are located outside protein coding regions, and as such, it is challenging interpret function by traditional approaches. Recent genome-wide functional genomics studies, such FANTOM5 ENCODE have uncovered a large number regulatory elements across different tissues or cell lines in genome. These findings provide an opportunity study interaction between disease-associated variants. Identifying diseased-related will shed light on understanding mechanisms how regulate gene expression ultimately result disease formation progression. In this study, we curated categorized 27,558 Mendelian variants, 20,964 complex 5,809 cancer predisposing germline 43,364 recurrent somatic mutations. Compared against nine types regions from projects, found that show distinctive propensity for particular elements. mutations 22-fold 10- fold significantly enriched promoter respectively (q<0.001), compared allele-frequency-matched genomic background. Separate two categories, 27-fold histone modification 10-fold chromatin physical 6-fold transcription promoters (q<0.001). Furthermore, share very similar distribution effects. We further within over 50% exon regions. Transcription promoters, methylation insulators highest density 472, 239, 72 per one million base pairs, respectively. Disease-associated categories preferentially results be useful overall about differences among pathogenic various

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