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Title: GENETIC DIVERSITY AND BACKGROUND LINKAGE DISEQUILIBRIUM IN NORTH AMERICAN HOLSTEIN CATTLE POPULATION

Author
item VALLEJO, R - PENN STATE UNIVERSITY
item LI, Y - PENN STATE UNIVERSITY
item ROGERS, G - UNIVERSITY OF TENNESSEE
item Ashwell, Melissa

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/22/2003
Publication Date: 5/22/2003
Citation: VALLEJO, R.L., LI, Y.L., ROGERS, G.W., ASHWELL, M.S. GENETIC DIVERSITY AND BACKGROUND LINKAGE DISEQUILIBRIUM IN NORTH AMERICAN HOLSTEIN CATTLE POPULATION. JOURNAL OF DAIRY SCIENCE 020639.R2, 2003.

Interpretive Summary: The objectives of this study were to (i) identify highly heterozygous Holstein bulls and their families to use for gene mapping studies; (ii) estimate the level of genetic diversity in these bulls; and (iii) determine how useful the associations between DNA markers and disease loci would be to precisely map genes responsible for effects on economically important traits. Twenty-three elite Holstein bulls that are not closely related to one another and widely used in the U.S. dairy industry were identified and studied at 54 DNA markers. The heterozygosity for the sample of elite Holstein bulls ranged from 0.43 to 0.80. This wide range of heterozygosity allows selection of the most heterozygous bulls to develop families for mapping complex disease/trait loci. Furthermore, the degree of genetic diversity observed in this purebred Holstein population is significant and actually allows the selection for traits of economic importance in the dairy industry. Results suggest that the observed associations between DNA markers in the bovine genome are not purely due to genetic drift and that some associations might be due to associations between markers and disease loci. This raises our hopes for finely localizing genes affecting complex traits in the U.S. Holstein dairy population using sophisticated mapping approaches. If refined statistical methods are not used to minimize the rate of false positives, the pinpointing of causal genes becomes difficult and may lead to further study of incorrect DNA regions.

Technical Abstract: The objectives of this study were to (i) identify highly heterozygous Holstein bulls that are least related as possible and widely used in the US dairy industry; (ii) quantify the level of genetic diversity in US Holstein cattle; and (iii) determine the extent of background linkage disequilibrium (BLD) and disease/trait associated linkage disequilibrium (DLD) in US Holstein population. Twenty-three elite Holstein bulls that are not closely related but were widely used in the US dairy industry were identified and genotyped on 54 microsatellite loci. The genotyping was performed on ABI PRISM 377 and ABI PRISM 3700 DNA sequencers (PE Applied Biosystems, CA), following PCR amplification with fluorescent dye-labeled primers. The heterozygosity for the sample of Holstein bulls ranged from 0.43 to 0.80. This wide range of heterozygosity allows selection of the most heterozygous bulls to develop informative families for complex disease/trait gene mapping studies. The degree of genetic diversity observed in this purebred Holstein population is significant and allows selection for traits of economic portance. As expected, there is extensive LD in the US Holstein population. About half of the syntenic marker pairs presented a typical pattern of LD produced by DLD. Most of the nonsyntenic marker pairs had a haplotype frequency distribution that resembles those due to BLD. These results suggest that the observed LD is not purely due to genetic drift and migration and that some might be due to DLD in the US Holstein population. This raises our hopes of successful fine-localization of genes affecting complex traits using LD mapping. In a few QTL cloning experiments some ideal conditions will be met and the QTL cloning will be successful. However, in most QTL cloning experiments these ideal conditions will not be met and the QTL cloning will not be trivial. If we do not use refined statistical methods that accounts for BLD when LD (generated by genetic drift and migration) extends over long regions, the localization of causal genes becomes difficult and may lead to study regions not containing the causal genes.