Abstract for presentation at 11th International Congress of Human Genetics

Diversity patterns of gonadotropin hormone beta gene family: reflection of gene history, meiotic and evolutionary forces

  • Prof Maris Laan, Institute of Molecular and Cell Biology, University of Tartu, Estonia
  • Pille Hallast, Institute of Molecular and Cell Biology, University of Tartu, Estonia
  • Marina Grigorova, Institute of Molecular and Cell Biology, University of Tartu, Estonia
  • Liina Nagirnaja, Institute of Molecular and Cell Biology, University of Tartu, Estonia

    • One of the gene families that has evolved in the primate lineage through segmental duplications is the Gonadotropin Hormone Beta subunit (GtHB) family, represented in human by 7 duplicated Luteinizing Hormone Beta (LHB) /Chorionic Gonadotropin Beta (CGB) genes located at 19q13.32 and 2 single-copy genes – Follicle-stimulating hormone beta (FSHB) at 11p13-p14 and TSHB at 1p13.2. GtHB genes have an essential role in human reproduction and all but placenta-specific CGB-s are expressed by anterior pituitary. We have addressed by resequencing the fine-scale variation and LD structure in LHB/CGB cluster and FSHB genomic regions as well as explored forces potentially shaping these genomic regions. Despite the evolutionary and functional relatedness, the GtHB family members exhibit contrasting diversity patterns. In the LHB/CGB region, characterized by high sequence homology between the duplicated genes, gene conversion has had an important role in spreading polymorphisms among duplicon copies and generating LD around them. The diversity level of LHB/CGB cluster is one of the highest reported for human genes. The directionality of gene conversion events seems to be determined by the localization of a predicted recombination ‘hotspot’ and ‘warm-spot’ in the vicinity of the most active gene conversion acceptor genes at the periphery of the cluster. Interestingly, diversity patterns of the two newest genes in the cluster, CGB1&CGB2, support their functionality but not earlier reported status as pseudogenes. In contrast to LHB/CGB genes, a single-copy FSHB located in a gene-poor genomic region is characterized by low diversity, no non-synonymous mutations and excess of SNPs with intermediate allele frequencies. There is evidence that the gene might be under the influence of balancing selection, which has favored the spread of only two worldwide FSHB variants. The study may have implications for understanding and regulating human fertility and individual’s reproductive success.

    Conference Organiser - ICMS Pty Ltd