Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder

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Predisposition to psychiatric disorders is due to the contribution of many genes involved in numerous molecular mechanisms. Since brain evolution has played a pivotal role in determining the success of the human species, the molecular pathways involved with the onset of mental illnesses are likely to be informative as we seek an understanding of the mechanisms involved in the evolution of human brain. Accordingly, we tested whether the genetics of psychiatric disorders is enriched for signatures of positive selection. We observed a strong finding related to the genetics of autism spectrum disorders (ASD): common risk alleles are enriched for genomic signatures of incomplete selection (loci where a selected allele has not yet reached fixation). The genes where these alleles map tend to be expressed in brain and pituitary tissues, to be involved in molecular mechanisms related to nervous system development, and surprisingly, to be associated with increased cognitive ability. Previous studies identified signatures of purifying selection in genes affected by ASD rare alleles. Accordingly, at least two different evolutionary mechanisms appear to be present in relation to ASD genetics: 1) rare disruptive alleles eliminated by purifying selection; 2) common alleles selected for their beneficial effects on cognitive skills. This scenario would explain ASD prevalence, which is higher than that expected for a trait under purifying selection, as the evolutionary cost of polygenic adaptation related to cognitive ability.

Vyšlo v časopise: Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder. PLoS Genet 13(2): e32767. doi:10.1371/journal.pgen.1006618
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1006618

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