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Identifying recent adaptations in large-scale genomic data.

Sharon R Grossman1, Kristian G Andersen, Ilya Shlyakhter

  • 1Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. grossman@broadinstitute.org

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|February 19, 2013
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Summary
This summary is machine-generated.

Researchers identified genetic variants linked to human adaptation by analyzing genome data. They found specific variants influencing traits and disease susceptibility, including one in Toll-like receptor 5 (TLR5) affecting immune signaling.

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Area of Science:

  • Human Genomics
  • Evolutionary Biology
  • Population Genetics

Background:

  • Hundreds of human genome regions show positive natural selection.
  • However, the specific adaptive traits and genetic variants remain largely unknown.

Purpose of the Study:

  • To identify and annotate candidate causal variants associated with positive natural selection in the human genome.
  • To create a catalog of variants for experimental validation.

Main Methods:

  • Utilized full-genome sequence variation data from the 1000 Genomes (1000G) Project.
  • Employed the composite of multiple signals (CMS) test to analyze 412 candidate signals.
  • Integrated functional annotation, protein structure modeling, epigenetics, and association studies.

Main Results:

  • Generated a catalog of 35 high-scoring nonsynonymous variants and 59 variants affecting gene expression (coding gene or lincRNA).
  • Identified numerous variants associated with infectious disease susceptibility and other phenotypes.
  • Experimentally validated a nonsynonymous variant in Toll-like receptor 5 (TLR5), demonstrating altered NF-κB signaling.

Conclusions:

  • The study provides a valuable resource of candidate adaptive variants for further research.
  • The findings highlight the role of specific genetic variants in human adaptation and disease.
  • Experimental characterization of TLR5 variant confirms its functional impact on immune response.