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Association of the protease inhibitor gene with production traits in Holstein dairy cattle.

Positional, comparative candidate gene analysis and previous quantitative trait loci linkage mapping results were used to search for candidate genes affecting milk production and reproduction traits in dairy cattle. The protease inhibitor (PI) gene was chosen for examination, and 5 single nucleotide polymorphisms were detected in coding regions of the gene by direct sequencing of reverse transcription-polymerase chain reaction products from a wide range of cattle tissues. A total of 6 different intragenic haplotypes were identified in North American Holstein population, and these were examined for associations with milk production traits in 24 half-sib families comprising 1007 sons utilizing a granddaughter design. One common haplotype was associated with increased milk and fat yields, increased productive life, and decreased somatic cell score. Another common haplotype was associated with decreased productive life and increased somatic cell score. One rare haplotype was associated with decreased milk, fat, and protein yields and increased milk protein percentage; another rare haplotype was associated with decreased milk yield, increased protein percentage, and decreased productive life. The observation that the PI gene is associated with analogous traits in humans demonstrates the effectiveness of the positional comparative candidate gene analysis that utilizes information about genes present in chromosomal regions with conserved synteny in other species.