Modeling primary ovarian insufficiency-associated loci in C. elegans identifies novel pathogenic allele of MSH5.

ABSTRACT:

Purpose

In women under the age of 40, primary ovarian insufficiency (POI) is a devastating diagnosis with significant prevalence of 1-4% (Rajkovic and Pangas, Semin Reprod Med. 35(3):231-40, 2017). POI is characterized by amenorrhea with elevated levels of follicle stimulating hormone (FSH) and reduced estrogen levels, mimicking the menopausal state. Genetic determinants account for just over 10% of POI cases, yet determining whether particular single nucleotide polymorphisms (SNPs) are pathogenic is challenging.

Methods

We performed exome sequencing on a cohort of women with POI. CRISPR mutagenesis was employed to create a mutation in a conserved amino acid in the nematode protein. Functional relevance was assessed by analysis of bivalents and aberrant DNA morphologies in d

SUBMITTER: Macaisne N 

PROVIDER: S-EPMC9174368 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature