Mouse sex ratio distortion

In collaboration with Czech colleagues, the PI recently reported a massive invasion of Mus musculus musculus Y chromosomes across the European mouse hybrid zone into Mus musculus domesticus territory at the Czech Bavarian border. This invasion has been accompanied by significant distortion of the sex ratio at localities where Y chromosome introgression has occurred. The goal of the project is to explain these observations.
Because this hybrid zone has been extensively studied, and the house mouse is a model organism, a genetic database already exists of DNA samples from more than 3000 mice sampled from the study area on the Czech Bavarian border, and thousands of these samples have previously been typed for allozymes, microsatellites and SNPs spread over all the autosomes and the X chromosome. In addition, the genetic database contains hundreds of sperm smears from the male mice sampled. The project will involve re-analysis and further genetic exploitation of this incredible genetic resource, in the light of the recently discovered Y chromosome invasion/sex distortion.

Candidate genome regions for sex ratio distortion can be identified by searching for marker loci with diplotypes unequally distributed among males and females in the database. The database can be divided according to three geographic categories: musculus territory, domesticus territory and domesticus territory where the musculus Y has invaded. A preliminary re-analysis of the existing database has identified a first candidate locus for sex ratio distortion CSRD1, situated in a low recombination area of an autosome. Three diplotypes at CSRD1 show significant differences from sex ratio parity in the database. Two of these involve an allele found at high frequency in the geographic region of Y invasion, and at low frequency elsewhere. By referring to the annotated mouse genome, five genes involved in male specific function have been identified within 5 cM of CSRD1. Identification of this first candidate locus serves to illustrate the potential power of this unique system for dissecting a sex ratio distortion effect in the house mouse, the main laboratory model for mammalian and human sex-functional genetics.