GEnetics of Male INfertility Initiative (GEMINI) was established to map the genetic architecture of severe male infertility
Male infertility due to spermatogenic failure is a common disorder found in 1% of men. Although the contribution of genetic predisposition is considered to be substantial, the genetic causes of severe male infertility have largely remained elusive. It is feasible that rare patient-specific mutations across a multitude of genes essential for germ cell development may lead to the manifestation of the disease. GEMINI, a multi-center study comprised of andrology investigators from 20 centers in nine countries, has recruited a cohort of 1850 patients and over 2000 controls to date (Spring 2021).
Current ongoing research activities are predominantly focused on identifying and describing the genetic composition of non-obstructive azoospermia (NOA) as the most severe type of male infertility. Whole-exome sequencing approach is applied to identify rare genetic alterations among the cases followed by variant prioritization and functional validation of most relevant findings. The long-term goals of GEMINI project include expanding the network and research interest to other types of male but also female infertility phenotypes.
Recent Posts
- Diverse monogenic subforms of human spermatogenic failure December 27, 2022
- Maris Laan visits OHSU for a year-long sabbatical November 14, 2022
- Variant PNLDC1, Defective piRNA Processing, and Azoospermia August 12, 2021
- Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure May 7, 2021
GEMINI employs cutting-edge software and experimental tools developed at or used in lead participating centers
Population sampling probability (PSAP)
Variant prioritization tool enabling a case-by-case analysis without a need for matching control samples. Wilfeft et al. 2016, Nat Genet
In vivo multiplex shRNA screening in mouse testis
A screening method suitable for a pooled validation of candidate genes suspected to have an impact on spermatogenesis. Ho et al. 2017, G3 (Bethesda)
Mammalian testis germ cell sorting
Flow cytometric sorting of five subpopulations of germ cells from various mammalian species in a manner compatible with downstream high-throughput studies. Lima et al. 2017, J Vis Exp
Validation in various animal models
In-house and collaborative efforts for functional validation of human disease variants with appropriate methods (e.g. knock-out or CRISPR-Cas9) and model organisms (including mouse, fruit fly and algae Chlamydomonas).