Genomic insights into the population history and adaptive traits of Latin American Criollo cattle.

Criollo cattle, the descendants of animals brought by Iberian colonists to the Americas, have been the subject of natural and human-mediated selection in novel tropical agroecological zones for centuries. Consequently, these breeds have evolved distinct characteristics such as resistance to diseases and exceptional heat tolerance. In addition to European taurine (Bos taurus) ancestry, it has been proposed that gene flow from African taurine and Asian indicine (Bos indicus) cattle has shaped the ancestry of Criollo cattle. In this study, we analysed Criollo breeds from Colombia and Venezuela using whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) array data to examine population structure and admixture at high resolution. Analysis of genetic structure and ancestry components provided evidence for African taurine and Asian indicine admixture in Criollo cattle. In addition, using WGS data, we detected selection signatures associated with a myriad of adaptive traits, revealing genes linked to thermotolerance, reproduction, fertility, immunity and distinct coat and skin coloration traits. This study underscores the remarkable adaptability of Criollo cattle and highlights the genetic richness and potential of these breeds in the face of climate change, habitat flux and disease challenges. Further research is warranted to leverage these findings for more effective and sustainable cattle breeding programmes.

Epidemiological investigation of insulin dysregulation in Shetland and Welsh ponies in Australia.

BACKGROUND: Insulin dysregulation (ID) is central to equine metabolic syndrome. There are limited epidemiological studies investigating dynamic testing of ID in ponies. OBJECTIVES: To evaluate prevalence and risk factors for ID through dynamic testing of hyperinsulinaemia (DHI) and insulin resistance (IR). STUDY DESIGN: Cross-sectional. METHODS: Sex, age, breed, height, cresty neck score (CNS), body condition score (BCS), laminitis, HMGA2:c.83G>A genotype and pituitary pars intermedia dysfunction (PPID) status were documented. Dynamic hyperinsulinaemia was diagnosed with an oral sugar test (OST) and IR with an insulin tolerance test (ITT). Owners completed surveys reporting activity, laminitis history and perception of body condition using a (1-9) visual analogue scale (VASo). Ordinal scores were converted to binary outcomes for CNS (≤2/5 or ≥3/5), BCS and VASo (≤6/9 or ≥7/9). Variables associated with insulin concentrations, glucose reduction after the ITT and laminitis were evaluated with mixed effects regression models accounting for random effects of farms. RESULTS: Among 167 ponies tested, median (range) age was 9 (4-21) years and BCS was 6 (4-8). Prevalence (95% confidence interval [CI]) of ID was 61 (53-68)%. Factors associated with insulin concentrations (estimate [95% CI]; µIU/mL) 60 min post-OST were: age (1.07 [1.02-1.11]), CNS (≥3/5, 1.52 [1.04-2.23]) and VASo (≥7/9, 1.75 [1.09-2.79]); and 90 min post-OST were: age (1.08 [1.03-1.12]), CNS (≥3/5, 1.80 [1.22-2.64]), VASo (≥7/9, 2.49 [1.52-4.08]) and sex (male, 0.64 [0.45-0.91]). Factors associated with glucose reduction after the ITT (estimate [95% CI]; %) were: age (-1.34 [-2.01 to -0.67]), sex (female, -6.21 [-11.68 to -0.74]) and VASo (≥7/9, -1.74 [-18.89 to -4.78]). Factors associated with laminitis (odds ratio [95% CI]) were DHI (4.60 [1.68-12.58]), IR (3.66 [1.26-10.61]) and PPID (11.75 [1.54-89.40]). MAIN LIMITATIONS: Single time-point sampling, laminitis definition and diet analysis. CONCLUSIONS: Ageing, being female and owner-perceived obesity were associated with ID.

Selection signatures for local and regional adaptation in Chinese Mongolian horse breeds reveal candidate genes for hoof health.

BACKGROUND: Thousands of years of natural and artificial selection since the domestication of the horse has shaped the distinctive genomes of Chinese Mongolian horse populations. Consequently, genomic signatures of selection can provide insights into the human-mediated selection history of specific traits and evolutionary adaptation to diverse environments. Here, we used genome-wide SNPs from five distinct Chinese Mongolian horse populations to identify genomic regions under selection for the population-specific traits, gait, black coat colour, and hoof quality. Other global breeds were used to identify regional-specific signatures of selection. RESULTS: We first identified the most significant selection peak for the Wushen horse in the region on ECA23 harbouring DMRT3, the major gene for gait. We detected selection signatures encompassing several genes in the Baicha Iron Hoof horse that represent good biological candidates for hoof health, including the CSPG4, PEAK1, EXPH5, WWP2 and HAS3 genes. In addition, an analysis of regional subgroups (Asian compared to European) identified a single locus on ECA3 containing the ZFPM1 gene that is a marker of selection for the major domestication event leading to the DOM2 horse clade. CONCLUSIONS: Genomic variation at these loci in the Baicha Iron Hoof may be leveraged in other horse populations to identify animals with superior hoof health or those at risk of hoof-related pathologies. The overlap between the selection signature in Asian horses with the DOM2 selection peak raises questions about the nature of horse domestication events, which may have involved a prehistoric clade other than DOM2 that has not yet been identified.

Genomic diversity and breed composition of Vietnamese smallholder dairy cows.

Vietnamese smallholder dairy cows (VDC) are the result of crossbreeding between different zebu (ZEB) and taurine dairy breeds through many undefined generations. Thus, the predominant breed composition of VDC is currently unknown. This study aimed to evaluate the level of genetic diversity and breed composition of VDC. The SNP data of 344 animals from 32 farms located across four dairy regions of Vietnam were collected and merged with genomic reference data, which included three ZEB breeds: Red Sindhi, Sahiwal and Brahman, three taurine breeds: Holstein (HOL), Jersey (JER) and Brown Swiss (BSW), and a composite breed: Chinese Yellow cattle. Diversity and admixture analyses were applied to the merged data set. The VDC were not excessively inbred, as indicated by very low inbreeding coefficients (Wright's FIS ranged from -0.017 to 0.003). The genetic fractions in the test herds suggested that the VDC are primarily composed of HOL (85.0%); however, JER (6.0%), BSW 5.3%) and ZEB (4.5%) had also contributed. Furthermore, major genotype groupings in the test herds were pure HOL (48%), B3:15/16HOL_1/16ZEB (22%) and B2:7/8HOL_1/8ZEB (12%). The genetic makeup of the VDC is mainly components of various dairy breeds but also has a small percentage of ZEB; thus, the VDC could be a good genetic base for selecting high milk-producing cows with some degree of adaptation to tropical conditions.

An Epigenetic Aging Clock for Cattle Using Portable Sequencing Technology.

Extensively grazed cattle are often mustered only once a year. Therefore, birthdates are typically unknown or inaccurate. Birthdates would be useful for deriving important traits (growth rate; calving interval), breed registrations, and making management decisions. Epigenetic clocks use methylation of DNA to predict an individual's age. An epigenetic clock for cattle could provide a solution to the challenges of industry birthdate recording. Here we derived the first epigenetic clock for tropically adapted cattle using portable sequencing devices from tail hair, a tissue which is widely used in industry for genotyping. Cattle (n = 66) with ages ranging from 0.35 to 15.7 years were sequenced using Oxford Nanopore Technologies MinION and methylation was called at CpG sites across the genome. Sites were then filtered and used to calculate a covariance relationship matrix based on methylation state. Best linear unbiased prediction was used with 10-fold cross validation to predict age. A second methylation relationship matrix was also calculated that contained sites associated with genes used in the dog and human epigenetic clocks. The correlation between predicted age and actual age was 0.71 for all sites and 0.60 for dog and human gene epigenetic clock sites. The mean absolute deviation was 1.4 years for animals aged less than 3 years of age, and 1.5 years for animals aged 3-10 years. This is the first reported epigenetic clock using industry relevant samples in cattle.

Genomic prediction using low-coverage portable Nanopore sequencing.

Most traits in livestock, crops and humans are polygenic, that is, a large number of loci contribute to genetic variation. Effects at these loci lie along a continuum ranging from common low-effect to rare high-effect variants that cumulatively contribute to the overall phenotype. Statistical methods to calculate the effect of these loci have been developed and can be used to predict phenotypes in new individuals. In agriculture, these methods are used to select superior individuals using genomic breeding values; in humans these methods are used to quantitatively measure an individual's disease risk, termed polygenic risk scores. Both fields typically use SNP array genotypes for the analysis. Recently, genotyping-by-sequencing has become popular, due to lower cost and greater genome coverage (including structural variants). Oxford Nanopore Technologies' (ONT) portable sequencers have the potential to combine the benefits genotyping-by-sequencing with portability and decreased turn-around time. This introduces the potential for in-house clinical genetic disease risk screening in humans or calculating genomic breeding values on-farm in agriculture. Here we demonstrate the potential of the later by calculating genomic breeding values for four traits in cattle using low-coverage ONT sequence data and comparing these breeding values to breeding values calculated from SNP arrays. At sequencing coverages between 2X and 4X the correlation between ONT breeding values and SNP array-based breeding values was > 0.92 when imputation was used and > 0.88 when no imputation was used. With an average sequencing coverage of 0.5x the correlation between the two methods was between 0.85 and 0.92 using imputation, depending on the trait. This suggests that ONT sequencing has potential for in clinic or on-farm genomic prediction, however, further work to validate these findings in a larger population still remains.

Comparison of Genetic Merit for Weight and Meat Traits between the Polled and Horned Cattle in Multiple Beef Breeds.

Breeding for polled animals is deemed the most practical solution to eradicate horns naturally and circumvent management costs and risks on health and welfare. However, there has been a historical reluctance by some farmers to select polled animals due to perceived lower productivity of their calves. This study has compared estimated breeding values (EBVs) between horned and polled animals (N = 2,466,785) for 12 production and carcass traits to assess historical (before 2000) and recent (2000-2018) genetic implications of poll breeding. Older generations of the polled animals in most breeds had significantly lower (Bonferroni-corrected p = 0.05) genetic merits for live (birth to maturity) and carcass weights, milk, meat quality, and fat content traits. Substantial gains of genetic potential were achieved during 2000 to 2018 in each breed, such that polled animals have significantly improved for the majority of traits studied. Generally, polled cohorts showed advantageous EBVs for live and carcass weights irrespective of the lower birth weights in some breeds. While Polled Brahman showed inferior production parameters, the poll genetics' effect size (d) and correlation (r) were very small on recent birth weight (d = -0.30, r = -0.08), 200 days (-0.19, -0.05), 400 days (-0.06, -0.02), 600 days (-0.05, -0.01), mature cow live weight (-0.08, -0.02), and carcass weight (-0.19, -0.05). In conclusion, although there is some evidence that historical selection for polled breeding animals may have reduced productivity, there is strong evidence that more recent selection for polled genotypes in the breeds studied has not resulted in any adverse effects on genetic merit.

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%), but resulted in one of the fastest rates of genetic gain ($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%), but this conventional breeding scenario resulted in the slowest rate of genetic gain ($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.

Genome-wide association study of multiple traits linked to heat tolerance in emmer-derived hexaploid wheat genotypes.

Heat stress tolerance in plants is a complex trait controlled by multiple genes of minor effect which are influenced by the environment and this makes breeding and selection complicated. Emmer wheat (Triticum dicoccon Schrank) carries valuable diversity that can be used to improve the heat tolerance of modern bread wheat. A diverse set of emmer-based genotypes was developed by crossing emmer wheat with hexaploid wheat. These materials, along with their hexaploid recurrent parents and commercial cultivars, were evaluated at optimum (E1) and heat stressed (E2) sowing times in the field for three consecutive years (2014-2016). The material was genotyped using the Infinium iSelect SNP 90K SNP Assay. The phenotypic data were combined across years within each sowing time and best linear unbiased estimators calculated for each genotype in each environment. These estimates were used for GWAS analysis. Significant phenotypic and genotypic variation was observed for all traits. A total of 125 and 142 marker-trait associations (MTAs) were identified in E1 and E2, respectively. The highest number of MTAs were observed on the A genome (106), followed by the B (105) and D (56) genomes. MTAs with pleiotropic effects within and across the environments were observed. Many of the MTAs found were reported previously for various traits, and a few significant MTAs under heat stress were new and linked to emmer genome. Genomic regions identified on chromosomes 2B and 3A had a significant positive impact on grain yield under stress with a 7% allelic effect. Genomic regions on chromosomes 1A and 4B contributed 11% and 9% of the variation for thousand kernel weight (TKW) under heat stress respectively. Following fine mapping, these regions could be used for marker-assisted selection to improve heat tolerance in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01222-3.

Selection in Australian Thoroughbred horses acts on a locus associated with early two-year old speed.

Thoroughbred horse racing is a global sport with major hubs in Europe, North America, Australasia and Japan. Regional preferences for certain traits have resulted in phenotypic variation that may result from adaptation to the local racing ecosystem. Here, we test the hypothesis that genes selected for regional phenotypic variation may be identified by analysis of selection signatures in pan-genomic SNP genotype data. Comparing Australian to non-Australian Thoroughbred horses (n = 99), the most highly differentiated loci in a composite selection signals (CSS) analysis were on ECA6 (34.75-34.85 Mb), ECA14 (33.2-33.52 Mb and 35.52-36.94 Mb) and ECA16 (24.28-26.52 Mb) in regions containing candidate genes for exercise adaptations including cardiac function (ARHGAP26, HBEGF, SRA1), synapse development and locomotion (APBB3, ATXN7, CLSTN3), stress response (NR3C1) and the skeletal muscle response to exercise (ARHGAP26, NDUFA2). In a genome-wide association study for field-measured speed in two-year-olds (n = 179) SNPs contained within the single association peak (33.2-35.6 Mb) overlapped with the ECA14 CSS signals and spanned a protocadherin gene cluster. Association tests using higher density SNP genotypes across the ECA14 locus identified a SNP within the PCDHGC5 gene associated with elite racing performance (n = 922). These results indicate that there may be differential selection for racing performance under racing and management conditions that are specific to certain geographic racing regions. In Australia breeders have principally selected horses for favourable genetic variants at loci containing genes that modulate behaviour, locomotion and skeletal muscle physiology that together appear to be contributing to early two-year-old speed.

Optimized Genetic Testing for Polledness in Multiple Breeds of Cattle.

Many breeds of modern cattle are naturally horned, and for sound husbandry management reasons the calves frequently undergo procedures to physically remove the horns by disbudding or dehorning. These procedures are however a welfare concern. Selective breeding for polledness - absence of horns - has been effective in some cattle breeds but not in others (Bos indicus genotypes) due in part to the complex genetics of horn phenotype. To address this problem different approaches to genetic testing which provide accurate early-in-life prediction of horn phenotype have been evaluated, initially using microsatellites (MSAT) and more recently single nucleotide polymorphism (SNP). A direct gene test is not effective given the genetic heterogeneity and large-sized sequence variants associated with polledness in different breeds. The current study investigated 39,943 animals of multiple breeds to assess the accuracy of available poll testing assays. While the standard SNP-based test was an improvement on the earlier MSAT haplotyping method, 1999 (9.69%) out of 20,636 animals tested with this SNP-based assay did not predict a genotype, most commonly associated with the Indicus-influenced breeds. The current study has developed an optimized poll gene test that resolved the vast majority of these 1999 unresolved animals, while the predicted genotypes of those previously resolved remained unchanged. Hence the optimized poll test successfully predicted a genotype in 99.96% of samples assessed. We demonstrated that a robust set of 5 SNPs can effectively determine PC and PF alleles and eliminate the ambiguous and undetermined results of poll gene testing previously identified as an issue in cattle.

A Population Genomics Analysis of the Native Irish Galway Sheep Breed.

The Galway sheep population is the only native Irish sheep breed and this livestock genetic resource is currently categorised as 'at-risk'. In the present study, comparative population genomics analyses of Galway sheep and other sheep populations of European origin were used to investigate the microevolution and recent genetic history of the breed. These analyses support the hypothesis that British Leicester sheep were used in the formation of the Galway. When compared to conventional and endangered breeds, the Galway breed was intermediate in effective population size, genomic inbreeding and runs of homozygosity. This indicates that, although the Galway breed is declining, it is still relatively genetically diverse and that conservation and management plans informed by genomic information may aid its recovery. The Galway breed also exhibited distinct genomic signatures of artificial or natural selection when compared to other breeds, which highlighted candidate genes that may be involved in production and health traits.

Genomic Characterisation of the Indigenous Irish Kerry Cattle Breed.

Kerry cattle are an endangered landrace heritage breed of cultural importance to Ireland. In the present study we have used genome-wide SNP array data to evaluate genomic diversity within the Kerry population and between Kerry cattle and other European breeds. Patterns of genetic differentiation and gene flow among breeds using phylogenetic trees with ancestry graphs highlighted historical gene flow from the British Shorthorn breed into the ancestral population of modern Kerry cattle. Principal component analysis (PCA) and genetic clustering emphasised the genetic distinctiveness of Kerry cattle relative to comparator British and European cattle breeds. Modelling of genetic effective population size (Ne) revealed a demographic trend of diminishing Ne over time and that recent estimated Ne values for the Kerry breed may be less than the threshold for sustainable genetic conservation. In addition, analysis of genome-wide autozygosity (FROH) showed that genomic inbreeding has increased significantly during the 20 years between 1992 and 2012. Finally, signatures of selection revealed genomic regions subject to natural and artificial selection as Kerry cattle adapted to the climate, physical geography and agro-ecology of southwest Ireland.

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., NCAPG-LCORL, 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.