Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection?

Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Research Abstract Details 

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Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Abstract Text:

Jan Freudenberg,Ying-Hui Fu,Louis J ,

Channels and developmental genes belong to the molecular key players in the human central nervous system (CNS). Mutations in these genes often cause monogenic neurological disease and interspecies comparisons had shown reduced divergence. On the other hand, accelerated evolution of genes with roles in neurotransmission and development had indicated widespread positive selection in hominids. In the present study, we hypothesized that recombination hotspots could be enriched at genes with particularly important role in the CNS, because at those loci beneficial mutations may occur on a highly constrained background and consequently increased recombination could promote their fixation. To test this hypothesis, we retrieved CNS genes based on keyword search, expression data and expert knowledge. Consistent with our hypothesis, we find an enrichment of hotspot predictions around genes that are retrieved by all three strategies. Moreover, when comparing human genes based on their Gene Ontology annotations, we find hotspot predictions preferentially located around channels and neurodevelopmental genes. Taken together with the distinct sequence evolution that was reported by comparative genomic studies, this finding indicates continued positive selection at many CNS gene loci. In support of this interpretation, we also find an enrichment of recombination hotspot predictions around conserved noncoding regions that were reported to display a signature of accelerated evolution in the human lineage. Widespread positive selection acting on CNS gene loci could relate to the high prevalence of human nervous system disorders with genetically complex inheritance, potentially under an ancestral susceptibility allele model.

Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Publishing Authors By Initials

J Freudenberg,YH Fu,LJ ,

For similar genetic processes: selection (genetics) research abstracts see: genetic processes: selection (genetics) research

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Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: European journal of human genetics : EJHG

VOLUME: 15

Page Numbers: 1071-8

Journal Abbreviation: Eur. J. Hum. Genet.

ISSN: 1018-4813

DAY: 13

MONTH: 06

YEAR: 2007

Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Information

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LANGUAGE: eng

NlmUniqueID: 9302235

Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Keywords Mesh Terms:

KEYWORDS: Selection (Genetics)

MESH TERMS: genetics

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Grant and Affiliation Information for Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection?

AFFILIATION: Department of Neurology, Institute of Human Genetics, University of California San Francisco, San Francisco, CA, USA. jan.freudenberg@ucsf.edu

Country: England

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MEDLINETA: Eur J Hum Genet

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