Comparison of Gene Editing Versus Conventional Breeding to Introgress the POLLED Allele Into the Tropically Adapted Australian Beef Cattle Population

Dehorning is the process of physically removing horns to protect animals and humans from injury, but the process is costly, unpleasant, and faces increasing public scrutiny. Genetic selection for polled (hornless), which is genetically dominant to horned, is a long-term solution to eliminate the need for dehorning. However, due to the limited number of polled Australian Brahman bulls, the northern Australian beef cattle population remains predominantly horned. The potential to use gene editing to produce high-genetic-merit polled cattle was recently demonstrated. To further explore the concept, this study simulated introgression of the POLLED allele into a tropically adapted Australian beef cattle population via conventional breeding or gene editing (top 1% or 10% of seedstock bulls/year) for 3 polled mating schemes and compared results to baseline selection on genetic merit (Japan Ox selection index, $JapOx) alone, over the course of 20 years. The baseline scenario did not significantly decrease the 20-year HORNED allele frequency (80$8.00/year). Compared to the baseline, the conventional breeding scenarios where polled bulls were preferentially used for breeding, regardless of their genetic merit, significantly decreased the 20-year HORNED allele frequency (30%), but resulted in a significantly slower rate of genetic gain ($6.70/year, P ≤ 0.05). The mating scheme that required the exclusive use of homozygous polled bulls, resulted in the lowest 20-year HORNED allele frequency (8$5.50/year). The addition of gene editing the top 1% or 10% of seedstock bull calves/year to each conventional breeding scenario resulted in significantly faster rates of genetic gain (up to $8.10/year, P ≤ 0.05). Overall, our study demonstrates that, due to the limited number of polled Australian Brahman bulls, strong selection pressure on polled will be necessary to meaningfully increase the number of polled animals in this population. Moreover, these scenarios illustrate how gene editing could be a tool for accelerating the development of high-genetic-merit homozygous polled sires to mitigate the current trade-off of slower genetic gain associated with decreasing HORNED allele frequency in the Australian Brahman population

A meta-assembly of selection signatures in cattle

Since domestication, significant genetic improvement has been achieved for many traits of commercial importance in cattle, including adaptation, appearance and production. In response to such intense selection pressures, the bovine genome has undergone changes at the underlying regions of functional genetic variants, which are termed "selection signatures". This article reviews 64 recent (2009-2015) investigations testing genomic diversity for departure from neutrality in worldwide cattle populations. In particular, we constructed a meta-assembly of 16,158 selection signatures for individual breeds and their archetype groups (European, African, Zebu and composite) from 56 genome-wide scans representing 70,743 animals of 90 pure and crossbred cattle breeds. Meta-selection-scores (MSS) were computed by combining published results at every given locus, within a sliding window span. MSS were adjusted for common samples across studies and were weighted for significance thresholds across and within studies. Published selection signatures show extensive coverage across the bovine genome, however, the meta-assembly provides a consensus profile of 263 genomic regions of which 141 were unique (113 were breed-specific) and 122 were shared across cattle archetypes. The most prominent peaks of MSS represent regions under selection across multiple populations and harboured genes of known major effects (coat color, polledness and muscle hypertrophy) and genes known to influence polygenic traits (stature, adaptation, feed efficiency, immunity, behaviour, reproduction, beef and dairy production). As the first meta-assembly of selection signatures, it offers novel insights about the hotspots of selective sweeps in the bovine genome, and this method could equally be applied to other species

Composite selection signals for complex traits exemplified through bovine stature using multibreed cohorts of European and African Bos taurus

Understanding the evolution and molecular architecture of complex traits is important in domestic animals. Due to phenotypic selection, genomic regions develop unique patterns of genetic diversity called signatures of selection, which are challenging to detect, especially for complex polygenic traits. In this study, we applied the composite selection signals (CSS) method to investigate evidence of positive selection in a complex polygenic trait by examining stature in phenotypically diverse cattle comprising 47 European and 8 African Bos taurus breeds, utilizing a panel of 38,033 SNPs genotyped on 1106 animals. CSS were computed for phenotypic contrasts between multibreed cohorts of cattle by classifying the breeds according to their documented wither height to detect the candidate regions under selection. Using the CSS method, clusters of signatures of selection were detected at 26 regions (9 in European and 17 in African cohorts) on 13 bovine autosomes. Using comparative mapping information on human height, 30 candidate genes mapped at 12 selection regions (on 8 autosomes) could be linked to bovine stature diversity. Of these 12 candidate gene regions, three contained known genes (i.e., NCAPGLCORL, FBP2-PTCH1, and PLAG1-CHCHD7) related to bovine stature, and nine were not previously described in cattle (five in European and four in African cohorts). Overall, this study demonstrates the utility of CSS coupled with strategies of combining multibreed datasets in the identification and discovery of genomic regions underlying complex traits. Characterization of multiple signatures of selection and their underlying candidate genes will elucidate the polygenic nature of stature across cattle breeds

A list of selection tests used in published studies on Bovine selection signatures.

<p>A list of selection tests used in published studies on Bovine selection signatures.</p

Meta-assembly of selection signatures in four groups within European, Zebu, African and Composite breeds of cattle.

<p>Meta-assembly of selection signatures in four groups within European, Zebu, African and Composite breeds of cattle.</p

Map of selection signature hotspots captured in the meta-assembly of cattle breeds and groups.

<p>Middle Panels labelled as “Cattle Breeds” and “Cattle Groups”, show the location of prominent regions in the cattle breeds and groups, respectively represented with the unique colours as shown in the legends. The clustered dots, within a locus, located on top of each other represent shared selection signatures across the breeds and groups, each of which has been validated in multiple investigations. Lower Panel labelled as “Gene density” shows distribution of bovine genes on each chromosome that ranges 0–80 genes/Mb (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153013#pone.0153013.s014" target="_blank">S7 Fig</a> shows high-resolution comparison of MSS and genes per Mb in European). Top Panel labelled as "Candidate Genes" shows genomic locations of a few major genes underlying the outstanding peaks representing classic selective sweep regions in the meta-assemblies. Complete list of prominent regions, localized top MSS and underlying genes within the groups and breeds of cattle are respectively shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153013#pone.0153013.s004" target="_blank">S4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153013#pone.0153013.s005" target="_blank">S5</a> Tables.</p

Summary of genome-wide scans on Bovine selection signatures.

<p>Summary of genome-wide scans on Bovine selection signatures.</p

Plot of relationship matrix and DNA score (<i>d</i>_<i>i</i>) weighting computed from 46 studies that published selection signature using European cattle.

<p><b><i>n</i></b>_{<b><i>i</i></b>} shows total number of DNA samples from European breed(s) from a particular study. The relationship score was computed as proportion of common samples between each pair of studies and it range between 0 and 1.</p

Meta-assembly of selection signatures of Holstein, Brown Swiss, Jersey, Simmental (Fleckvieh), Angus, Charolais, Hanwoo, Hereford, Limousin, Piedmontese, Brahman, Gir and Nellore cattle.

<p>Meta-assembly of selection signatures of Holstein, Brown Swiss, Jersey, Simmental (Fleckvieh), Angus, Charolais, Hanwoo, Hereford, Limousin, Piedmontese, Brahman, Gir and Nellore cattle.</p

Meta-assembly of selection signatures of Belgian Blue, Braunvieh, Guernsey, Italian Brown, Marchigiana, Murray Grey, Norwegian Red, Romagnola, Shorthorn, Santa Gertrudis, NDama and Sheko.

<p>Meta-assembly of selection signatures of Belgian Blue, Braunvieh, Guernsey, Italian Brown, Marchigiana, Murray Grey, Norwegian Red, Romagnola, Shorthorn, Santa Gertrudis, NDama and Sheko.</p