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Functional implications of splicing polymorphisms in the human genome.

Abstract：

:Proper splicing is often crucial for gene functioning and its disruption may be strongly deleterious. Nevertheless, even the essential for splicing canonical dinucleotides of the splice sites are often polymorphic. Here, we use data from The 1000 Genomes Project to study single-nucleotide polymorphisms (SNPs) in the canonical dinucleotides. Splice sites carrying SNPs are enriched in weakly expressed genes and in rarely used alternative splice sites. Genes with disrupted splice sites tend to have low selective constraint, and the splice sites disrupted by SNPs are less likely to be conserved in mouse. Furthermore, SNPs are enriched in splice sites whose effects on gene function are minor: splice sites located outside of protein-coding regions, in shorter exons, closer to the 3'-ends of proteins, and outside of functional protein domains. Most of these effects are more pronounced for high-frequency SNPs. Despite these trends, many of the polymorphic sites may still substantially affect the function of the corresponding genes. A number of the observed splice site-disrupting SNPs, including several high-frequency ones, were found among mutations described in OMIM.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Kurmangaliyev YZ,Sutormin RA,Naumenko SA,Bazykin GA,Gelfand MS

doi

10.1093/hmg/ddt200

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

3449-59

issue

17

eissn

0964-6906

issn

1460-2083

pii

ddt200

journal_volume

22

pub_type

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