Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders

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Abstract

In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins. We discuss the possibility that segregation distortion during spermatogenesis accounts for a subset of ASD mutations. Finally, we detected modern-human-specific alleles in DYRK1A and TCF4. These variants are located within regions that display chromatin features typical of transcriptional enhancers in several brain areas, strongly suggesting a regulatory role. These SNPs thus represent candidates for association with neurodevelopmental disorders, and await experimental validation in future studies.

Original languageEnglish
Pages (from-to)6116
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Jul 21 2017

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Neanderthals
Genes
Genetic Selection
Hominidae
Spermatogenesis
Intelligence
Cognition
Chromatin
Single Nucleotide Polymorphism
Alleles
Mutation
Brain
Autism Spectrum Disorder
Neurodevelopmental Disorders

Keywords

  • Journal Article

Cite this

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title = "Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders",
abstract = "In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins. We discuss the possibility that segregation distortion during spermatogenesis accounts for a subset of ASD mutations. Finally, we detected modern-human-specific alleles in DYRK1A and TCF4. These variants are located within regions that display chromatin features typical of transcriptional enhancers in several brain areas, strongly suggesting a regulatory role. These SNPs thus represent candidates for association with neurodevelopmental disorders, and await experimental validation in future studies.",
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author = "Alessandra Mozzi and Diego Forni and Rachele Cagliani and Uberto Pozzoli and Mario Clerici and Manuela Sironi",
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T1 - Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders

AU - Mozzi, Alessandra

AU - Forni, Diego

AU - Cagliani, Rachele

AU - Pozzoli, Uberto

AU - Clerici, Mario

AU - Sironi, Manuela

PY - 2017/7/21

Y1 - 2017/7/21

N2 - In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins. We discuss the possibility that segregation distortion during spermatogenesis accounts for a subset of ASD mutations. Finally, we detected modern-human-specific alleles in DYRK1A and TCF4. These variants are located within regions that display chromatin features typical of transcriptional enhancers in several brain areas, strongly suggesting a regulatory role. These SNPs thus represent candidates for association with neurodevelopmental disorders, and await experimental validation in future studies.

AB - In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins. We discuss the possibility that segregation distortion during spermatogenesis accounts for a subset of ASD mutations. Finally, we detected modern-human-specific alleles in DYRK1A and TCF4. These variants are located within regions that display chromatin features typical of transcriptional enhancers in several brain areas, strongly suggesting a regulatory role. These SNPs thus represent candidates for association with neurodevelopmental disorders, and await experimental validation in future studies.

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