title: Composite selection signals can localize the trait specific genomic regions in multi-breed populations of cattle and sheep.
abstract: BACKGROUND
  Discerning the traits evolving under neutral conditions from those traits evolving rapidly because of various selection pressures is a great challenge. We propose a new method, composite selection signals (CSS), which unifies the multiple pieces of selection evidence from the rank distribution of its diverse constituent tests. The extreme CSS scores capture highly differentiated loci and underlying common variants hauling excess haplotype homozygosity in the samples of a target population.
  
  
  RESULTS
  The data on high-density genotypes were analyzed for evidence of an association with either polledness or double muscling in various cohorts of cattle and sheep. In cattle, extreme CSS scores were found in the candidate regions on autosome BTA-1 and BTA-2, flanking the POLL locus and MSTN gene, for polledness and double muscling, respectively. In sheep, the regions with extreme scores were localized on autosome OAR-2 harbouring the MSTN gene for double muscling and on OAR-10 harbouring the RXFP2 gene for polledness. In comparison to the constituent tests, there was a partial agreement between the signals at the four candidate loci; however, they consistently identified additional genomic regions harbouring no known genes. Persuasively, our list of all the additional significant CSS regions contains genes that have been successfully implicated to secondary phenotypic diversity among several subpopulations in our data. For example, the method identified a strong selection signature for stature in cattle capturing selective sweeps harbouring UQCC-GDF5 and PLAG1-CHCHD7 gene regions on BTA-13 and BTA-14, respectively. Both gene pairs have been previously associated with height in humans, while PLAG1-CHCHD7 has also been reported for stature in cattle. In the additional analysis, CSS identified significant regions harbouring multiple genes for various traits under selection in European cattle including polledness, adaptation, metabolism, growth rate, stature, immunity, reproduction traits and some other candidate genes for dairy and beef production.
  
  
  CONCLUSIONS
  CSS successfully localized the candidate regions in validation datasets as well as identified previously known and novel regions for various traits experiencing selection pressure. Together, the results demonstrate the utility of CSS by its improved power, reduced false positives and high-resolution of selection signals as compared to individual constituent tests.
authors.affiliation: ReproGen - Animal Bioscience Group, Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden NSW 2570, Australia. imtiaz.randhawa@sydney.edu.au.
authors.forename: Imtiaz Ahmed Sajid
authors.initials: IA
authors.lastname: Randhawa
authors.forename: Mehar Singh
authors.initials: MS
authors.lastname: Khatkar
authors.forename: Peter Campbell
authors.initials: PC
authors.lastname: Thomson
authors.forename: Herman Willem
authors.initials: HW
authors.lastname: Raadsma
mesh_terms: D000818:Animals; D001947:Breeding; D002417:Cattle / Q000235:genetics*; D002874:Chromosome Mapping; D056426:Genetic Loci; D005838:Genotype; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*; D034561:Sheep, Domestic / Q000235:genetics*