Supplementary material for article: X chromosome variants were associated to heritable fertility traits, in two bovine populations.

X chromosome variants were associated to heritable fertility traits, in two bovine populations. Fortes, Porto-Neto et al. 2019. Background: Targeting phenotypes related to bull fertility, such as sperm morphology and sperm DNA fragmentation can help identify mutations that limit reproduction capacity. Twenty-five fertility-related phenotypes were measured as indicators of bull fertility (1,099 Brahman bulls and 1,719 Tropical Composite bulls). Measurements included standard bull breeding soundness measures (e.g. sperm motility), scrotal circumference, sperm DNA fragmentation and sperm protamine deficiency. These phenotypes were used in a genome-wide association studies that aimed to detect quantitative trait loci (QTL). Results: Genomic analyses confirmed some QTL in both breeds (Brahman and Tropical Composites) while others were breed specific. For example, only in Brahman cattle, we identified polymorphisms associated (P < 10-16) with sperm midpiece morphological abnormalities. The QTL identified and mutations occurring only in Bos indicus suggest that the gene A-kinase anchoring protein (AKAP)14 might be related to midpiece abnormalities in Brahman. Associated mutations described herein corroborate with known genes affecting spermatogenesis, including those in the AKAP and testis-expressed gene (TEX) families. Polymorphism associations suggest that AKAP14 and TEX11 are positional and functional candidate genes in chromosome X affecting bull fertility. Most significant variants and QTLs mapped to chromosome X. These results add evidence to a mammalian specialization of X that evolved to harbor genes linked to spermatogenesis, as similarly observed in mice and humans. Some variants in X may affect more than one genetically correlated trait (r2 ~ 0.33–0.51), such as sperm morphology and sperm DNA fragmentation. Correlations and shared QTL support the hypothesis that these phenotypes have the same underlying cause: faulty spermatogenesis. In addition, heritabilities for sperm DNA fragmentation and sperm protamine deficiency were moderate (h2 ~ 0.21–0.47), being the first reported estimates. Conclusions: Genetic improvement for bull fertility is possible through selective breeding. Genomic selection for bull fertility might be more accurate if the X chromosome mutations that underlie the discovered QTL are included in the analyses. Variants associated with bull fertility accumulate in the X chromosome, as they do in humans and mice, thus, suggesting specialization of this chromosome.