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Refined mapping of twinning rate QTL on bovine chromosome 5 and analysis of IGF1 as a positional candidate gene^1,2

Eui-Soo Kim^*, Xianwei Shi^*,#, Ozden Cobanoglu, Kent Weigel, P. Jeffrey Berger and Brian W. Kirkpatrick^*,

^* Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706 , Department of Dairy Sciences, University of Wisconsin-Madison, Madison, WI, 53706 , Department of Animal Science, Namik Kemal University, Turkey , Department of Animal Science, Iowa State University, Ames, IA, 50010 ^# College of Animal Science and Technology, Yunnan Agricultural University, China

bwkirkpa{at}wisc.edu

Abstract

Twinning in cattle is a complex trait that is associated with economic loss and health issues such as abortion, dystocia, and reduced calf survival. Twinning rate QTL have been previously detected on chromosome 5 in the North American Holstein and Norwegian dairy cattle populations and in a USDA herd selected for high twinning rate. In previous work with the North American Holstein population, the strongest evidence for a QTL was obtained from analysis of an extended, multiple generation family. Using additional animals, an increased density of SNP marker association tests and a combined linkage and linkage disequilibrium mapping method , the position of this QTL was refined in the North American Holstein population. Two sets of twinning rate predicted transmitting abilities estimated during 2 different time periods in the North American dairy cattle population were used to provide validation of results. A total of 106 SNPs and 3 microsatellites were used to scan the genomic region between 5 and 80 Mb on chromosome 5. Combined linkage-linkage disequilibrium analysis identified significant evidence for QTL within the 25 to 35 MB and 64 to 70 Mb regions of chromosome 5. IGF1 was examined as a positional candidate gene and a SNP in intron 2 of IGF1 was significantly associated with twinning rate using both data sets (P=0.003 and P=1.05x10^-6). Replication of this association in other cattle populations will be required to examine the extent of linkage disequilibrium with the underlying quantitative trait nucleotide across breeds.

Key Words: bovine • cattle • IGF1 • ovulation • twin