Female- or Male-biased Offspring Generated by Targeted Distortion of Sex Chromosome Transmission

In animal breeding, female or male progeny is preferred depending on the use of the animals. Especially in livestock, offspring with undesired sex is of low economic value and often culled. Here we achieve targeted sex ratio distortion in the mouse, leveraging components of a selfish supergene, the t-haplotype. Utilizing its central element, the t-responder, we generate a highly “selfless” genetic element disabling transgenic sperm. When integrated on the X or Y chromosome it results in a high prevalence of non-transgenic offspring of the desired sex. Our strategy overcomes key limitations of existing strategies, including compromised animal health, reduced fertility, and fully transgenic breeding stocks, which might foster acceptance of its application to livestock. The efficacy of our approach marks a groundbreaking advance in animal breeding. Overall design: Total RNA-Seq and ChIP-seq (H3K27Ac) samples from whole testis of WT C57BL/6J mice at different ages p.p. (d12, d16, d24 and adult stage).