Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/31/2011
Publication Date: 12/1/2011
Citation: Van Raden, P.M., Olson, K.M., Null, D.J., Hutchison, J.L. 2011. Harmful recessive effects on fertility detected by absence of homozygous haplotypes. Journal of Dairy Science. 94(12):6153-6161. Interpretive Summary: Based on genomic testing, a method was developed to discover lethal defects by detecting the absence of homozygous haplotypes. Five new lethal recessive defects were discovered: 3 in Holsteins, 1 in Jerseys, and 1 in Brown Swiss. Haplotype testing revealed that effect on sire conception rate for those 5 new as well as 2 previously known defects were negative and consistent with a lethal recessive. Once animals have been genotyped, dairy farmers could avoid mating carrier animals without further testing expense using the new haplotype test, thereby saving time, increasing profitability, and reducing those defects in the population.
Technical Abstract: Five new lethal recessive defects were discovered in Holsteins, Jerseys, and Brown Swiss by examining haplotypes that had 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 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 -3.1% to -3.7%, which was slightly smaller than the -3.9% to -4.6% expected for lethal recessives but slightly larger than estimated effects for previously known lethal alleles of -2.5% for brachyspina and -2.9% 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 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.