Harmful recessive effects on fertility detected by absence of homozygous haplotypes

Five new recessive defects were discovered in Holsteins, Jerseys, and Brown Swiss by examining haplotypes that had a high population frequency but were never homozygous. The method required genotypes only from apparently normal individuals and not from affected embryos. Genotypes from the BovineSNP50 BeadChip (Illumina, San Diego, CA) were examined for 58,453 Holsteins, 5,288 Jerseys, and 1,991 Brown Swiss with genotypes in the North American database. Haplotypes with a length of ≤ 75 markers were obtained. Eleven candidate haplotypes were identified, with the earliest carrier born before 1980; 7 to 90 homozygous haplotypes were expected, but none were observed in the genomic data. Expected numbers were calculated using either the actual mating pattern or assuming random mating. Probability of observing no homozygotes ranged from 0.0002 for 7 to 10⁻⁴⁵ for 90 expected homozygotes. Phenotypic effects were confirmed for 5 of the 11 candidate haplotypes using 14,911,387 Holstein, 830,391 Jersey, and 68,443 Brown Swiss records for conception rate. Estimated effect for interaction of carrier service sire with carrier maternal grandsire ranged from -3.0 to -3.7 percentage points, which was slightly smaller than the -3.9 to -4.6 percentage points expected for lethal recessives but slightly larger than estimated effects for previously known lethal alleles of -2.5 percentage points for brachyspina and -2.9 percentage points for complex vertebral malformation. Conception rate was coded as a success only if the gestation went to term or the cow was confirmed to be pregnant. Estimated effect of carrier interaction for stillbirth rate based on 10,876,597 Holstein and 25,456 Jersey records was small. Thus, lethal effects may include conception, gestation, and stillbirth losses. Carrier frequency has been >20% for many years for the confirmed defect in Jerseys and is currently 16% for the defect in Brown Swiss. The 3 defects discovered in Holsteins have carrier frequencies of 2.7 to 6.4% in the current population. For previously known defects, map locations and lack of homozygotes were consistent with the literature and lethal recessive inheritance, but numbers of expected homozygotes for some were small because of low frequency. Very large genotypic and phenotypic data sets allow efficient detection of smaller and less frequent effects. Haplotype tests can help breeders avoid carrier matings for such defects and reduce future frequencies.