Patterns of ancestry, signatures of natural selection, and genetic association with stature in Western African pygmies

PLoS Genet. 2012;8(4):e1002641. doi: 10.1371/journal.pgen.1002641. Epub 2012 Apr 26.

Abstract

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Biological
  • Africa, Western
  • African Continental Ancestry Group
  • Biological Evolution*
  • Body Height / genetics*
  • Chromosome Mapping
  • Dwarfism* / genetics
  • Ethnic Groups / genetics*
  • Genetic Association Studies
  • Genome, Human
  • Growth Hormone / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Selection, Genetic
  • Suppressor of Cytokine Signaling Proteins / genetics

Substances

  • DOCK3 protein, human
  • Guanine Nucleotide Exchange Factors
  • Nerve Tissue Proteins
  • Suppressor of Cytokine Signaling Proteins
  • cytokine inducible SH2-containing protein
  • Insulin-Like Growth Factor I
  • Growth Hormone