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Abstract
Background'Selection signatures' delimit regions of the genome that are, or have been, functionally important and have therefore been under either natural or artificial selection. In this study, two different and complementary methods--integrated Haplotype Homozygosity Score (|iHS|) and population differentiation index (FST)--were applied to identify traces of decades of intensive artificial selection for traits of economic importance in modern cattle.ResultsWe scanned the genome of a diverse set of dairy and beef breeds from Germany, Canada and Australia genotyped with a 50 K SNP panel. Across breeds, a total of 109 extreme |iHS| values exceeded the empirical threshold level of 5% with 19, 27, 9, 10 and 17 outliers in Holstein, Brown Swiss, Australian Angus, Hereford and Simmental, respectively. Annotating the regions harboring clustered |iHS| signals revealed a panel of interesting candidate genes like SPATA17, MGAT1, PGRMC2 and ACTC1, COL23A1, MATN2, respectively, in the context of reproduction and muscle formation. In a further step, a new Bayesian FST-based approach was applied with a set of geographically separated populations including Holstein, Brown Swiss, Simmental, North American Angus and Piedmontese for detecting differentiated loci. In total, 127 regions exceeding the 2.5 per cent threshold of the empirical posterior distribution were identified as extremely differentiated. In a substantial number (56 out of 127 cases) the extreme FST values were found to be positioned in poor gene content regions which deviated significantly (p < 0.05) from the expectation assuming a random distribution. However, significant FST values were found in regions of some relevant genes such as SMCP and FGF1.ConclusionsOverall, 236 regions putatively subject to recent positive selection in the cattle genome were detected. Both |iHS| and FST suggested selection in the vicinity of the Sialic acid binding Ig-like lectin 5 gene on BTA18. This region was recently reported to be a major QTL with strong effects on productive life and fertility traits in Holstein cattle. We conclude that high-resolution genome scans of selection signatures can be used to identify genomic regions contributing to within- and inter-breed phenotypic variation.
Highlights
The domestication of cattle (Bos taurus and Bos taurus indicus) 8,000-10,000 years ago [1] had a significant impact on human civilization
Applying the |integrated Haplotype Homozygosity Score (iHS)| test with a new Bayesian method of Population fixation index (FST), we report a panel of 236 regions putatively subject to recent positive selection confirming the higher differentiation index and longer haplotype consistency for a strong QTL recently detected in Holstein cattle
The cattle genome offers an opportunity to test the power of genome-wide analyses, as it has extensive linkage disequilibrium (LD) [2,21] caused by intensive selection, and it is expected that selection footprints would be correlated with genes affecting production traits or fitness
Summary
The domestication of cattle (Bos taurus and Bos taurus indicus) 8,000-10,000 years ago [1] had a significant impact on human civilization. Voight et al (2006) [12] developed the “integrated Haplotype Score” (|iHS|), an extension of EHH, based on the comparison of EHH between derived and ancestor alleles within a population In this concept, directional selection favoring a new mutation results in a rapid increase in the frequency of the selected allele along with the background haplotype in which the mutation arose. Directional selection favoring a new mutation results in a rapid increase in the frequency of the selected allele along with the background haplotype in which the mutation arose This phenomenon increases linkage disequilibrium (LD) on the chromosomes which harbor the derived (selected) allele, but not the unselected allele, which acts as a “control”. The |iHS| statistic may continue to identify regions of high LD surrounding the selected site, but may not detect selection at the selected region itself because fixation will eliminate variation at and near the selected site
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