Evolutionary origin of germline pathogenic variants in human DNA mismatch repair genes.

ABSTRACT:

Background

Mismatch repair (MMR) system is evolutionarily conserved for genome stability maintenance. Germline pathogenic variants (PVs) in MMR genes that lead to MMR functional deficiency are associated with high cancer risk. Knowing the evolutionary origin of germline PVs in human MMR genes will facilitate understanding the biological base of MMR deficiency in cancer. However, systematic knowledge is lacking to address the issue. In this study, we performed a comprehensive analysis to know the evolutionary origin of human MMR PVs.

Methods

We retrieved MMR gene variants from the ClinVar database. The genomes of 100 vertebrates were collected from the UCSC genome browser and ancient human sequencing data were obtained through comprehensive data mining. Cross-species conserva

SUBMITTER: Lei H 

PROVIDER: S-EPMC10823654 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature