Haplotype structure of FSHB, the beta-subunit gene for fertility-associated follicle-stimulating hormone: possible influence of balancing selection

Ann Hum Genet. 2007 Jan;71(Pt 1):18-28. doi: 10.1111/j.1469-1809.2006.00299.x.


Follicle-stimulating hormone (FSH) is essential for human reproduction. The unique functions of this hormone are provided by the FSH receptor-binding beta-subunit encoded by the FSHB gene. Resequencing and genotyping of FSHB in three European, two Asian and one African population, as well as in the great apes (chimpanzee, gorilla, orangutan), revealed low diversity and significant excess of polymorphisms with intermediate frequency alleles. Statistical tests for FSHB showed deviations from neutrality in all populations suggesting a possible effect of balancing selection. Two core haplotypes were identified (carried by 76-96.6% of each population's sample), the sequences of which are clearly separated from each other. As fertility most directly affects an organism's fitness, the carriers of these haplotypes have apparently had more success in human history to contribute to the next generation. There is a preliminary observation suggesting that the second most frequent FSHB haplotype may be associated with rapid conception success in females. Interestingly, the same haplotype is related to an ancestral FSHB variant shared with the ancestor of the great apes. The determination of the functional consequence of the two core FSHB variants may have implications for understanding and regulating human fertility, as well as in assisting infertility treatments.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Fertility / genetics*
  • Follicle Stimulating Hormone, beta Subunit / genetics*
  • Follicle Stimulating Hormone, beta Subunit / metabolism
  • Gorilla gorilla / genetics
  • Haplotypes*
  • Humans
  • Pan troglodytes / genetics
  • Pongo pygmaeus / genetics
  • Selection, Genetic*
  • Sequence Alignment


  • Follicle Stimulating Hormone, beta Subunit