Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
| Autor: | Younghee Lee, Anuar Konkashbaev, Eric R. Gamazon, Nancy J. Cox, Eske M. Derks |
|---|---|
| Přispěvatelé: | Other departments, APH - Mental Health, Adult Psychiatry |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RNA Splicing Science Population Genome-wide association study Single-nucleotide polymorphism Biology Quantitative trait locus Polymorphism Single Nucleotide Article 03 medical and health sciences Humans Disease Nucleotide Motifs Selection Genetic education Selection (genetic algorithm) Genetics education.field_of_study Multidisciplinary Natural selection Haplotype Chromosome Mapping Introns Genetics Population 030104 developmental biology Genetic Loci Evolutionary biology Medicine Human genome Genome-Wide Association Study |
| Zdroj: | Scientific reports, 7(1). Nature Publishing Group Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) Scientific Reports |
| Popis: | We performed a whole-genome scan of genetic variants in splicing regulatory elements (SREs) and evaluated the extent to which natural selection has shaped extant patterns of variation in SREs. We investigated the degree of differentiation of single nucleotide polymorphisms (SNPs) in SREs among human populations and applied long-range haplotype- and multilocus allelic differentiation-based methods to detect selection signatures. We describe an approach, sampling a large number of loci across the genome from functional classes and using the consensus from multiple tests, for identifying candidates for selection signals. SRE SNPs in various SNP functional classes show different patterns of population differentiation compared with their non-SRE counterparts. Intronic regions display a greater enrichment for extreme population differentiation among the potentially tissue-dependent transcript ratio quantitative trait loci (trQTLs) than SRE SNPs in general and includ outlier trQTLs for cross-population composite likelihood ratio, suggesting that incorporation of context annotation for regulatory variation may lead to improved detection of signature of selection on these loci. The proportion of extremely rare SNPs disrupting SREs is significantly higher in European than in African samples. The approach developed here will be broadly useful for studies of function and disease-associated variation in the human genome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|