25 research outputs found

    Classic Selective Sweeps Revealed by Massive Sequencing in Cattle

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    <div><p>Human driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern cattle. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying domestication-related genes that ultimately may help to further genetically improve this economically important animal. To this end, we employed a panel of more than 15 million autosomal SNPs identified from re-sequencing of 43 Fleckvieh animals. We mainly applied two somewhat complementary statistics, the integrated Haplotype Homozygosity Score (iHS) reflecting primarily ongoing selection, and the Composite of Likelihood Ratio (CLR) having the most power to detect completed selection after fixation of the advantageous allele. We find 106 candidate selection regions, many of which are harboring genes related to phenotypes relevant in domestication, such as coat coloring pattern, neurobehavioral functioning and sensory perception including KIT, MITF, MC1R, NRG4, Erbb4, TMEM132D and TAS2R16, among others. To further investigate the relationship between genes with signatures of selection and genes identified in QTL mapping studies, we use a sample of 3062 animals to perform four genome-wide association analyses using appearance traits, body size and somatic cell count. We show that regions associated with coat coloring significantly (P<0.0001) overlap with the candidate selection regions, suggesting that the selection signals we identify are associated with traits known to be affected by selection during domestication. Results also provide further evidence regarding the complexity of the genetics underlying coat coloring in cattle. This study illustrates the potential of population genetic approaches for identifying genomic regions affecting domestication-related phenotypes and further helps to identify specific regions targeted by selection during speciation, domestication and breed formation of cattle. We also show that Linkage Disequilibrium (LD) decays in cattle at a much faster rate than previously thought.</p></div

    Fleckvieh animals with different coat coloring phenotypes.

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    <p>(A) without spot, (B) spotted and (C) red head. The figures were kindly supplied by BAYERN-GENETIK GmbH (<a href="http://www.fleckvieh.de" target="_blank">http://www.fleckvieh.de</a>).</p

    A schematic representation of LD plotted as a function of distance.

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    <p>The decay of LD estimated from bovine SNP arrays of 50K and 700K (n = 1,293) are compared with the sequence data (n = 43). The inner plot displays a higher resolution of LD in pair-wise distances of <250 Kb from sequence data of which <i>r<sup>2</sup></i> values are down-sampled from all pairwise estimates (for more details see Material and Methods).</p

    The visualization of the signals revealed by association analyses for coat coloring traits.

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    <p>GWAS are presented for the proportion of daughters with red head (A1) and the proportion of daughters without spotting (B1) based on 15,182,131 imputed variants in 3062 Fleckvieh animals. In (B1) the largest effects emerge from eight SNPs summarized in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004148#pgen-1004148-t002" target="_blank">Table 2</a> with MITF (P = <i>2.65e-58</i>) and <i>KIT/KDR</i> (P = 2.46e-44) at the top. Together, <i>KIT/KDR</i> and MITF explained 36.25% of the residual variance of the trait in the studied population. A2 and B2 are the corresponding quantile-quantile plots. Shown in blue is the quantile-quantile plot resulting from removal of all SNPs in the region of significant genes listed in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004148#pgen-1004148-t002" target="_blank">Table 2</a>, for both traits. The shaded area is the 95% concentration band under the null hypothesis of no association. Panels C and D are detailed overviews of the associated regions on BTA6 and BTA22, respectively. Variants in the promoter (defined to encompass 1,000 bp upstream of the transcription start), in the untranslated regions (UTR) and in the amino-acid coding region are highlighted with different color. The red triangles indicate the genomic positions of KIT and MITF genes.</p

    Genome-wide visualization of selection candidates (top 1% signals) localized by |iHS| (A) and CLR (B) metrics.

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    <p>Each dot represents a non-overlapping window of 40 Kb along BTA1 to BTA29. Panels C and D show a high resolution illustration of the candidate regions for the <i>KIT/KDR</i> and <i>MITF</i> genes, respectively on BTA6 and BTA22. |iHS| is plotted in overlapping windows of 40 Kb in steps of 5 Kb, and a grid size of 5 Kb was chosen for the CLR statistic. Finally, Panel E is a haplotype bifurcation plot of the <i>KIT/KDR</i> genes.</p

    A partial list of candidate regions revealed by both iHS and CLR analyses.

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    1<p>Only best candidate genes are shown.</p>2<p>Position stands at the middle of the top hitch-hiked window in the candidate region.</p
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