A predicted deleterious allele of the essential meiosis gene MND1, present in ~ 3% of East Asians, does not disrupt reproduction in mice

Molecular Human Reproduction
Tina N TranJohn C Schimenti

Abstract

Infertility is a major health problem affecting ~15% of couples worldwide. Except for cases involving readily detectable chromosome aberrations, confident identification of a causative genetic defect is problematic. Despite the advent of genome sequencing for diagnostic purposes, the preponderance of segregating genetic variants complicates identification of culprit genetic alleles or mutations. Many algorithms have been developed to predict the effects of 'variants of unknown significance', typically single nucleotide polymorphisms (SNPs), but these predictions are not sufficiently accurate for clinical action. As part of a project to identify population variants that impact fertility, we have been generating clustered regularly interspaced short palindromic repeats-Cas9 edited mouse models of suspect SNPs in genes that are known to be required for fertility in mice. Here, we present data on a non-synonymous (amino acid altering) SNP (rs140107488) in the meiosis gene Mnd1, which is predicted bioinformatically to be deleterious to protein function. We report that when modeled in mice, this allele (MND1K85M), which is present at an allele frequency of ~ 3% in East Asians, has no discernable effect upon fertility, fecundity or ga...Continue Reading

References

Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yi-Kai ChenTing-Fang Wang
Apr 19, 2005·Nature Structural & Molecular Biology·Galina V PetukhovaR Daniel Camerini-Otero
Dec 7, 2013·Nucleic Acids Research·Roberto J PezzaR Daniel Camerini-Otero
Jun 20, 2014·Nature Communications·Dmitry V BugreevAlexander V Mazin
Oct 2, 2014·Genetics·Priti SinghEwelina Bolcun-Filas
Jun 7, 2015·Genome Research·Gaurav K VarshneyShawn M Burgess
Sep 21, 2016·Annual Review of Genetics·Stephen Gray, Paula E Cohen

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Citations

May 14, 2020·Molecular Human Reproduction·Diego Hernández-LópezRosana Rodríguez-Casuriaga
Oct 20, 2020·Human Molecular Genetics·Xinbao DingJohn C Schimenti
Jan 13, 2021·Trends in Molecular Medicine·Xinbao Ding, John C Schimenti
Aug 20, 2021·Nature Communications·Priti SinghJohn C Schimenti

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