Selection Signatures in Worldwide Sheep Populations

The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments

Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection

Genomic structure in a global collection of domesticated sheep reveals a history of artificial selection for horn loss and traits relating to pigmentation, reproduction, and body size

Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep

Stefan Hiendleder is a member of the International Sheep Genomics ConsortiumIn sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal’s health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization–time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.Michael P. Heaton, Theodore S. Kalbfleisch, Dustin T. Petrik, Barry Simpson, James W. Kijas, Michael L. Clawson, Carol G. Chitko-McKown, Gregory P. Harhay, Kreg A. Leymaster, the International Sheep Genomics Consortiu

Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection

Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species. © 2012 Kijas et al

Geographic origin of breed development and diversity.

<p>Breeds were genotyped from the Americas, Africa, Asia, and the domestication centre in present-day Iran and Turkey (referred to throughout as South-West Asia). The majority of breeds genotyped were developed in Europe (given in detail at right). Breed names and their abbreviations are given in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001258#pbio.1001258.s012" target="_blank">Table S1</a>. Marker heterozygosity within each breed compared against increasing physical distance from the domestication centre. Breeds used during SNP discovery are shown using filled circles. Haplotype sharing at 25–50 Kb between Merinos and other breeds (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001258#pbio.1001258.s008" target="_blank">Figure S8</a>) was plotted against heterozygosity to reveal a major influence of Merino admixture on the genetic diversity of European breeds. Breed-specific values for expected heterozygosity and haplotype sharing are given in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001258#pbio.1001258.s015" target="_blank">Table S4</a> to allow identification of populations with outlier values.</p

Genome-wide distribution of global <i>F</i>_ST.

<p>The amount of differentiation, measured as <i>F</i>_ST, was estimated within each breed by comparison to all other breeds. Global <i>F</i>_ST is the average for each SNP across all 74 HapMap breeds, meaning common signals present in multiple breeds are preferentially detected. SNP were ordered in genomic order with OAR1 at left. The highest peak is on OAR10.</p

Selection for sheep without horns (poll).

<p>Animals from two breeds with horns (Dorset Horn and Merino) were pooled and compared with two polled breeds (Poll Dorset and Poll Merino). Pairwise <i>F</i>_ST was calculated between the two groups of animals for all 49,034 SNP, before smoothed values were plotted in order across the genome (top panel). A strong selection signal was observed on Chromosome 10 (SNP number 27,878–29,558 with the signal peak at SNP <i>OAR10_29546872</i>). Pairwise <i>F</i>_ST was also calculated between horned breeds (green line) or between polled breeds (blue line) before the smoothed values were plotted across Chromosome 10 (bottom panel). The peak was only observed where horned breeds were compared with polled breeds, verifying that the signal relates to the long-standing husbandry practise of selecting animals for the absence of horns.</p

Common selection signals.

<p>The number of breeds that showed divergent selection is shown as a function of genomic position (A). Selection peaks were defined as regions with smoothed <i>F</i>_ST in excess of one standard deviation either above (positive selection; blue line) or below the genome-wide average (balancing selection; green line). Four regions were identified with shared positive selection peaks in 30 or more breeds (the chromosomal number is given above each peak). Similarly, five peaks were identified where 20 or more populations shared balancing selection, including the MHC region on OAR 20. One signal was common to each of three separate populations of Texel (B). Pairwise <i>F</i>_ST was calculated between Texel and all other animals, which revealed a strong selection on sheep Chromosome 2 above the <i>GDF8</i> gene, which underpins a breed defining phenotype.</p