Exploring the Potential Genetic Heterogeneity in the Incidence of Hoof Disorders in Austrian Fleckvieh and Braunvieh Cattle.

Genetic heterogeneity denotes the situation when different genetic architectures underlying diverse populations result in the same phenotype. In this study, we explore the genetic background underlying differences in the incidence of hoof disorders between Braunvieh and Fleckvieh cattle in the context of genetic heterogeneity between the breeds. Despite potentially higher power of testing due to twice as large sample size, none of the SNPs was significantly associated with the total number of hoof disorders in Fleckvieh, while 15 SNPs were significant in Braunvieh. The most promising candidate genes in Braunvieh were as follows: on BTA1, which causes arthritis in rats; on BTA4, which affects skeletal muscles in mice; on BTA5, which causes disease phenotypes related to the skeleton in humans, mice, and zebrafish; and on BTA6, which causes decreased susceptibility to injury in mice. Some of the significant SNPs (BTA1, BTA4, BTA5, BTA13, and BTA16) revealed allelic heterogeneity-i.e., different allele frequencies between Fleckvieh and Braunvieh. Some of the significant regions (BTA1, BTA5, BTA13, and BTA16) correlated to inter-breed differences in linkage disequilibrium (LD) structure and may thus represent false-positive heterogeneity. However, positions on BTA6 (), BTA14, and BTA24 mark Braunvieh-specific regions. We hypothesize that the observed genetic heterogeneity of hoof disorders is a by-product of different selection goals defined for the analyzed breeds-toward dairy production in Braunvieh and toward beef production in Fleckvieh. Based on the current dataset, it is not possible to unequivocally confirm or exclude the hypothesis of genetic heterogeneity in the susceptibility to hoof disorders between Fleckvieh and Braunvieh. The main reason for the problem is that the potential heterogeneity was explored through SNP-phenotype associations and not through causal mutations, due to a limited SNP density offered by the SNP-chip. The rationale against genetic heterogeneity comprises a limited power of detection of true associations as well as differences in the length of LD blocks and in linkage phase between breeds. On the other hand, different selection goals defined for the analyzed breeds accompanied by no systematic, genome-wide differences in LD structure between the breeds favor the heterogeneity hypothesis at some smaller genomic regions.