Patterns and mechanisms of sex ratio distortion in the Collaborative Cross mouse mapping population.

Document Type

Article

Publication Date

11-2021

Publication Title

Genetics

Keywords

JGM

JAX Source

Genetics 2021 Nov; 219(3):iyab136

Volume

219

Issue

3

ISSN

1943-2631

PMID

34740238

DOI

https://doi.org/10.1093/genetics/iyab136

Grant

GM133415

Abstract

In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, and are not mediated by random maternal effects. SRD exhibits a heritable component, but QTL mapping analyses fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We explore several potential complex genetic mechanisms for SRD, including allelic interactions leading to sex-biased lethality, genetic sex reversal, chromosome drive mediated by sex-linked selfish elements, and incompatibilities between specific maternal and paternal genotypes. We show that no one mechanism offers a singular explanation for this population-wide SRD. Instead, our data present preliminary evidence for the action of distinct mechanisms of SRD at play in different strains. Taken together, our work exposes the pervasiveness of SRD in the CC population and nominates the CC as a powerful resource for investigating diverse genetic causes of biased sex chromosome transmission.

Comments

The authors gratefully acknowledge the contribution of the
Histopathology and Microscopy Scientific Services at The Jackson
Laboratory for expert assistance with the work described in this
publication. They are also indebted to Racheal Wallace for conserving cage cards from all CC mating units, enabling the compilation of comprehensive breeding records from this mouse population. They also thank Candice Baker and Cat Lutz for sharing breeding data from CC-RIX crosses.

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