Species: human
Mutation name: None
type: naturally occurring
fertility: fertile
Comment: Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Stolk L et al. To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-?B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility. Wei K et al. (2003) Exonuclease 1 (Exo1) is a 5'-3' exonuclease that interacts with MutS and MutL homologs and has been implicated in the excision step of DNA mismatch repair. To investigate the role of Exo1 in mammalian mismatch repair and assess its importance for tumorigenesis and meiosis, we generated an Exo1 mutant mouse line. Analysis of Exo1(-/-) cells for mismatch repair activity in vitro showed that Exo1 is required for the repair of base:base and single-base insertion/deletion mismatches in both 5' and 3' nick-directed repair. The repair defect in Exo1(-/-) cells also caused elevated microsatellite instability at a mononucleotide repeat marker and a significant increase in mutation rate at the Hprt locus. Exo1(-/-) animals displayed reduced survival and increased susceptibility to the development of lymphomas. In addition, Exo1(-/-) male and female mice were sterile because of a meiotic defect. Meiosis in Exo1(-/-) animals proceeded through prophase I; however, the chromosomes exhibited dynamic loss of chiasmata during metaphase I, resulting in meiotic failure and apoptosis. Our results show that mammalian Exo1 functions in mutation avoidance and is essential for male and female meiosis.//////////////////

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Variation analysis of EXO1 gene in Chinese patients with premature ovarian failure. Su S et al. (2016) Exonuclease 1 (EXO1) is required for both DNA repair and meiosis. Inactivation of EXO1 gene in mice leads to infertility. This study aimed to investigate whether variants in the EXO1 gene contribute to human premature ovarian failure (POF). The coding region of EXO1 was sequenced in 186 Han Chinese patients with non-syndromic POF. No plausible mutation was detected. The results suggest that mutations in the coding region of EXO1 may not be responsible for POF in Han Chinese women.//////////////////