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ABSTRACT: A previous genome-wide search with a moderate density 10K marker set identified many marker associations with twinning rate, either through single-marker analysis or combined linkage-linkage disequilibrium (LLD; haplotype) analysis. The objective of the current study was to validate putative marker associations using an independent set of phenotypic data. Holstein bulls (n = 921) from 100 paternal half-sib families were genotyped. Twinning rate predicted transmitting abilities were calculated using calving records from 1994 to 1998 (Data I) and 1999 to 2006 (Data II), and the underlying liability scores from threshold model analysis were used as the trait in marker association analyses. The previous analysis used 201 bulls with daughter records in Data I. In the current analysis, this was increased to 434, providing a revised estimate of effect and significance. Bulls with daughter records in Data II totaled 851, and analysis of this data provided the validation of results from analysis of Data I. Single nucleotide polymorphisms (SNPs) were selected to validate previously significant single-marker associations and LLD results. Bulls were genotyped for a total of 306 markers. Nine of 13 LLD regions located on chromosomes 1, 2, 3, 6, 9, 22, 23(2) and 26 were validated, showing significant results for both Data I and II. Association analysis revealed 55 of 174 markers validated, equating to a single-marker validation rate of 31%. Stepwise backward elimination and cross-validation analyses identified 18 SNPs for use in a final reduced marker panel explaining 34% of the genetic variation, and to allow prediction of genetic merit for twinning rate.
Animal Genetics 03/2010; 41(4):406-16. · 2.40 Impact Factor
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ABSTRACT: A previous genome-wide search with a moderate-density 10,000-SNP set identified many marker associations with twinning rate on BTA14 through either single-marker analysis or combined linkage-linkage disequilibrium (LLD; haplotype) analysis. The objective of the current study was to fine-map putative QTL using a more densely populated marker map and both a larger and an independent set of phenotypic data. Holstein bulls (n = 921) from 100 paternal half-sib families were genotyped for 129 SNP markers that included both original and additionally selected markers for increasing marker density in the targeted 34 megabase region. Twinning rate predicted transmitting abilities were calculated using calving records from 1994 to 1998 (data I) and 1999 to 2006 (data II), and the underlying liability scores from threshold model analysis were used as the trait in marker association analyses. The previous analysis used 201 bulls with daughter records in data I. In the current analysis, this was increased to 434, providing a revised estimate of effect and significance. Bulls with daughter records in data II totaled 851, and analysis of these data provided an opportunity for an independent analysis separate from data I. Single-marker association and LLD analyses were performed. Fifteen significant single-marker associations were found (minimally exceeding P < 8.74 x 10(-3)) to concur between data sets. Three and 12 regions in data I and data II, respectively, showed positive results for the presence of QTL from LLD analysis (P < 0.001) within the respective data sets. After combining results from single-marker association, LLD analysis, and model-building strategies, 3 QTL were identified on BTA14. Based on single-marker results from data II, BTA14 harbors QTL responsible for approximately 24% of the variation in twinning rate predicted transmitting ability.
Journal of Animal Science 03/2010; 88(8):2556-64. · 2.10 Impact Factor
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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 detected previously on BTA5 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, we refined the position of this QTL 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 SNP and 3 microsatellites were used to scan the genomic region between 5 and 80 Mb on BTA5. Combined linkage-linkage disequilibrium analysis identified significant evidence for QTL within the 25- to 35-Mb and 64- to 70-Mb regions of BTA5. The IGF-1 gene (IGF1) was examined as a positional candidate gene and an SNP in intron 2 of IGF1 was significantly associated with twinning rate by using both data sets (P = 0.003 and P = 1.05 x 10(-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.
Journal of Animal Science 12/2008; 87(3):835-43. · 2.10 Impact Factor
