title: The role of GHR and IGF1 genes in the genetic determination of African pygmies' short stature.
abstract: African pygmies are at the lower extreme of human variation in adult stature and many evolutionary hypotheses have been proposed to explain this phenotype. We showed in a recent study that the difference in average stature of about 10 cm observed between contemporary pygmies and neighboring non-pygmies has a genetic component. Nevertheless, the genetic basis of African pygmies' short stature remains unknown. Using a candidate-gene approach, we show that intronic polymorphisms in GH receptor (GHR) and insulin-like growth factor 1 (IGF1) genes present outlying values of the genetic distance between Baka pygmies and their non-pygmy Nzimé neighbors. We further show that GHR and IGF1 genes have experienced divergent natural selection pressures between pygmies and non-pygmies throughout evolution. In addition, these SNPs are associated with stature in a sample composed of 60 pygmies and 30 non-pygmies and this association remains significant when correcting for population structure for the GHR locus. We conclude that the GHR and IGF1 genes may have a role in African pygmies' short stature. The use of phenotypically contrasted populations is a promising strategy to identify new variants associated with complex traits in humans.
authors.affiliation: CNRS-MNHN-Université Paris 7, UMR 7206 Ecoanthropology and Ethnobiology, Paris, France. nbecker@mnhn.fr
authors.forename: Noémie S A
authors.initials: NS
authors.lastname: Becker
authors.forename: Paul
authors.initials: P
authors.lastname: Verdu
authors.forename: Myriam
authors.initials: M
authors.lastname: Georges
authors.forename: Philippe
authors.initials: P
authors.lastname: Duquesnoy
authors.forename: Alain
authors.initials: A
authors.lastname: Froment
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Bouc
authors.forename: Evelyne
authors.initials: E
authors.lastname: Heyer
mesh_terms: D000328:Adult; D001827:Body Height / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018401:Sample Size
chemical_list: D008565:Membrane Proteins; C405010:delta-hGHR; D007334:Insulin-Like Growth Factor I