摘要
Abstract
Genomic mosaicism arising from mosaic variants is a phenomenon that describes the presence of a cell or cell populations with different genome compositions from the germline cells of an individual.It comprises all types of genetic variants.A large proportion of childhood genetic disorders are defined as being de novo,meaning that the disease-causing mutations are only detected in the proband,not in any of the parents.Population studies show that 80% of the de novo mutations arise from the paternal haplotype,that is,from paternal sperm mosaicism.This review provides a summary of the types and detection strategies of sperm mosaicism.In addition,it provides discussions on how recent studies demonstrated that genomic mosaic mutations in parents,especially those in the paternal sperms,could be inherited by the offspring and cause childhood disorders.According to the previous findings of the author's research team,sperm mosaicism derived from early embryogenesis and primordial germ cell stages can explain 5% to 20% of the de novo mutations related to clinical phenotypes and can serve as an important predictor of both rare and complex disorders.Sperm mosaicism shows great potential for clinical genetic diagnosis and consultations.Based on the published literature,the author suggests that,large-scale screening for de novo sperm mosaic mutations and population-based genetic screening should be conducted in future studies,which will greatly enhance the risk assessment in the offspring and effectively improve the genetic health at the population level.Implementation of direct sperm detection for de novo mutations will significantly increase the efficiency of the stratification of patient cohorts and improve recurrence risk assessment for future births.Future research in the field should be focused on the impact of environmental and lifestyle factors on the health of the offspring through sperms and their modeling of mutation signatures.In addition,targeted in vitro modeling of sperm mutations will also be a promising direction.关键词
嵌合现象/精子嵌合变异/等位基因比例/新发变异/综述Key words
Mosaicism/Sperm mosaicism/Allelic fraction/de novo variant/Review
