| Autor: |
Wanjun Gu, Gurguis, Christopher I., Zhou, Jin J., Yihua Zhu, Ko, Eun-A., Jae-Hong Ko, Ting Wang, Tong Zhou |
| Předmět: |
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| Zdroj: |
Genome Biology & Evolution; Oct2015, Vol. 7 Issue 10, p2929-2940, 12p |
| Abstrakt: |
Genetic variation arising from single nucleotide polymorphisms (SNPs) is ubiquitously found among human populations. While disease-causing variants are known in some cases, identifying functional or causative variants for most human diseases remains a challenging task. Rare SNPs, rather than commonones, are thought to bemore important in the pathology ofmost human diseases. We propose that rare SNPs should be divided into two categories dependent on whether the minor alleles are derived or ancestral. Derived alleles are less likely to have been purified by evolutionary processes and may bemore likely to induce deleterious effects.We therefore hypothesized that the rare SNPs with derived minor alleleswould bemore important for human diseases and predicted that these variants would have larger functional or structural consequences relative to the rare variants for which the minor alleles are ancestral.Wesystematically investigated the consequences of the exonic SNPs on protein function,mRNAstructure, and translation. Wefound that the functional and structural consequences aremore significant for the rare exonic variants forwhich theminor alleles are derived. However, this pattern is reversed when the minor alleles are ancestral. Thus, the rare exonic SNPs with derived minor alleles are more likely to be deleterious. Age estimation of rare SNPs confirms that these potentially deleterious SNPs are recently evolved in the human population. These results have important implications for understanding the function of genetic variations in human exonic regions and for prioritizing functional SNPs in genome-wide association studies of human diseases. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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