[Show abstract][Hide abstract] ABSTRACT: Following domestication, sheep (Ovis aries) have become an essential farmed animals across the world through adaptation to a diverse range of environments and varied production systems. Climate-mediated selective pressure has shaped phenotypic variation and has left genetic "footprints" in the genome of breeds raised in different agro-ecological zones. Unlike numerous studies that have searched for evidence of selection using only population genetics data, here, we conducted an integrated co-analysis of environmental data with SNP variation. By examining 49,034 SNPs from 32 old, autochthonous sheep breeds that are adapted to a spectrum of different regional climates, we identified 230 SNPs with evidence for selection that is likely due to climate-mediated pressure. Among them, 189 (82%) showed significant correlation (P ≤ 0.05) between allele frequency and climatic variables in a larger set of native populations from a worldwide range of geographic areas and climates. Gene ontology analysis of genes co-located with significant SNPs identified 17 candidates related to GTPase regulator and peptide receptor activities in the biological processes of energy metabolism and endocrine and autoimmune regulation. We also observed high linkage disequilibrium and significant extended haplotype homozygosity (EHH) for the core haplotype TBC1D12-CH1 of TBC1D12. The global frequency distribution of the core haplotype and allele OAR22_18929579-A showed an apparent geographic pattern and significant (P ≤ 0.05) correlations with climatic variation. Our results imply that adaptations to local climates have shaped the spatial distribution of some variants and they are candidates to underpin adaptive variation in sheep.
Molecular Biology and Evolution 12/2014; · 14.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNPs) have become the marker of choice for genetic studies in organisms of conservation, commercial, or biological interest. Most SNP discovery projects in non-model organisms apply a strategy for identifying putative SNPs based on filtering rules that account for random sequencing errors. Here, we analyze data used to develop 4723 novel SNPs for the commercially important deep-sea fish, orange roughy (Hoplostethus atlanticus), in order to measure the impact of not accounting for systematic sequencing errors when filtering identified polymorphisms to be added to the SNP chip. We used SAMtools to identify polymorphisms in a Velvet assembly of genomic DNA sequence data from seven individuals. The resulting set of polymorphisms were filtered to minimise ‘bycatch’ – polymorphisms caused by sequencing or assembly error. An Illumina Infinium SNP chip was used to genotype a final set of 7,714 polymorphisms across 1,734 individuals. Five predictors of SNP validity were examined for their effect on the probability of obtaining an assayable SNP: depth of coverage, number of reads that support a variant, polymorphism type (e.g., A/C), strand-bias, and SNP probe design score. Our results support a strategy of filtering out systematic sequencing errors in order to improve the efficiency of SNP discovery. We show that blastx can be used as an efficient tool to identify single-copy genomic regions in the absence of a reference genome. The results have implications for research aiming to identify SNPs and build SNP genotyping assays for non-model organisms.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Abstract Text: High-throughput genomic data present an enormous challenge to researchers, due to the “large P small N” problem. Recently a machine learning method, Random Forests (RF), has gained the popularity in addressing these problems. In this study, we examined the utility of RF in two livestock genome-wide association study (GWAS) datasets - a Spanish sheep pigmentation data and a tropical cattle pregnancy status data. The comparison of top 10 ranking SNPs identified by RF to single-marker GWAS methods found that: 1) RF confirmed the most strongly associated SNP (s26449) being the closest to the sheep pigmentation gene MCR1; 2) Five out of the top 10 SNPs identified by RF were close to the genes previously reported to link with reproductive performance in human or other species. The results indicate that RF can potentially be used in GWAS as an initial screening tool for candidate genes.
10th World Congress on Genetics Applied to Livestock Production; 08/2014
[Show abstract][Hide abstract] ABSTRACT: Abstract Text: This study proposed to use genotypes from pooled DNA samples of progeny to evaluate sires’ performance in a commercial flock. Blood samples were collected from 786 one year old Merino sheep in a commercial flock in southern Victoria, Australia. Animals were grouped into cohorts by dag score phenotype and sex. Eighty blood samples were collected within each cohort and randomly allocated to two equally sized pools. Pooled samples were assayed with the Ovine SNP 50 chip and allele frequencies estimated for each SNP in each pool. Blood was also collected from 33 sires of the commercial flock and genotyped. Sire allele contributions were estimated and these contributions were not randomly distributed across pool dag scores (P = 0.015). Genotyping pooled DNA of progeny and genotyping sires can be utilized as an estimate of sire performance for a difficult to measure, but commercially important trait.
Keywords: genotype, phenotype, pooled DNA
10th World Congress on Genetics Applied to Livestock Production; 08/2014
[Show abstract][Hide abstract] ABSTRACT: Abstract Text: Understanding genetic relatedness between individuals, sire groups and breeds underpins genomic selection and GWAS. Here, we describe a new estimate of genetic relatedness using normalized compression distance (NCD). Clustering of Sheep breeds inferred by NCD broadly reflects SNP correlation using standard multi-dimensional scaling. The clustering appears consistent with country of origin and population history. For example, the 4 British sheep meat breeds (Poll Dorset, Southdown, Suffolk and White Suffolk) clearly cluster with each other, but separate to unrelated breeds (Border Leicester, Merino and Texel). We show that the compression-based relationship matrix (CRM) and the genomic relationship matrix (GRM) are closely related. The quadratic relationship between pairwise NCD (CRM) and pairwise SNP correlation (GRM) implies CRM will perform better with closely related individuals, while the converse is true for GRM. For example, CRM resolves Merino from Poll Merino where GRM cannot.
Keywords: Genetic relationship matrix, Information compression, Sheep
10th World Congress on Genetics Applied to Livestock Production; 08/2014
[Show abstract][Hide abstract] ABSTRACT: We inferred a step-wise pattern of changing ancestral demography using whole-genome sequence data from four domestic sheep (Ovis aries) and four wild sheep (O. canadensis and O. dalli). The inferred demography indicates clear differences between the wild sheep and domestic sheep. Furthermore we identified marked changes in effective population size which correspond to known historical events, including glaciation events and sheep domestication. Keywords: demography effective population size runs of homozygosity sequence error correction Introduction
Proceedings, 10 th World Congress of Genetics Applied to Livestock Production, Vancouver, Canada; 08/2014
[Show abstract][Hide abstract] ABSTRACT: Sheep (Ovis aries) have been well adapted to thrive in a diverse range of climates during the domestication and breed development process. These climate-mediated selective pressures have shown to influence phenotypic variation within and among breeds and, meanwhile, left genetic “footprints” in their genome. Unlike numerous studies that searched for evidence of selection using only population genetic data, here we have scanned the sheep genome for selection signals by integrating genetic and climatic data. From the International Sheep HapMap Project, genome-wide data of ca. 50K SNPs in a diverse collection of 32 old and autochthonous breeds, which have been under different regional climates for a long term, were selected for the analyses. We first performed a variety of selection tests to detect variants under natural selective pressures. We demonstrated strong evidence for selective signals at a total of 230 SNPs associated with local adaptation to different climates. A great majority (82%, 189/230) of the candidate SNPs showed significant (P ˂ 0.05) correlations between allele frequencies and climatic variables in a large subset of native populations from a world-wide range of geographic origins and climates. Our results imply that adaptations to local climates have shaped the spatial distribution of particular variants and, thus, such loci are likely involved in sheep adaptation to environmental challenges. Further molecular and functional studies of candidate genes close to significant markers will help to elucidate the genetic architecture of climate-mediated adaptive traits in sheep and other farm animals.
34th International Society of Animal Genetics (ISAG), Xi’an, China; 07/2014
[Show abstract][Hide abstract] ABSTRACT: The extent of linkage disequilibrium (LD) between genetic loci has implications for both association studies and the accuracy of genomic prediction. To characterise the persistence of LD in diverse sheep breeds, two SNP genotyping platforms were used. First, existing SNP genotypes from 63 breeds obtained using the ovine SNP50 BeadChip (49 034 loci) were used to estimate LD decay in populations with contrasting levels of genetic diversity. Given the paucity of marker pairs separated by short physical distances on the SNP50 BeadChip, genotyping was subsequently performed for four breeds using the recently developed ovine HD BeadChip that assays approximately 600 000 SNPs with an average genomic spacing of 5 kb. This facilitated a highly accurate estimate of LD over short genomic distances (<30 kb) and revealed LD varies considerably between sheep breeds. Further, sheep appear to contain generally lower levels of LD than do other domestic species, likely a reflection of aspects of their past population history.
[Show abstract][Hide abstract] ABSTRACT: Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.
[Show abstract][Hide abstract] ABSTRACT: Summary To date, investigations of genetic diversity and the origins of domestication in sheep have utilised autosomal microsatellites and variation in the mitochondrial genome. We present the first analysis of both domestic and wild sheep using genetic markers residing on the ovine Y chromosome. Analysis of a single nucleotide polymorphism (oY1) in the SRY promoter region revealed that allele A-oY1 was present in all wild bighorn sheep (Ovis canadensis), two subspecies of thinhorn sheep (Ovis dalli), European Mouflon (Ovis musimon) and the Barbary (Ammontragis lervia). A-oY1 also had the highest frequency (71.4%) within 458 domestic sheep drawn from 65 breeds sampled from Africa, Asia, Australia, the Caribbean, Europe, the Middle East and Central Asia. Sequence analysis of a second locus, microsatellite SRYM18, revealed a compound repeat array displaying fixed differences, which identified bighorn and thinhorn sheep as distinct from the European Mouflon and domestic animals. Combined genotypic data identified 11 male-specific haplotypes that represented at least two separate lineages. Investigation of the geographical distribution of each haplotype revealed that one (H6) was both very common and widespread in the global sample of domestic breeds. The remaining haplotypes each displayed more restricted and informative distributions. For example, H5 was likely founded following the domestication of European breeds and was used to trace the recent transportation of animals to both the Caribbean and Australia. A high rate of Y chromosomal dispersal appears to have taken place during the development of domestic sheep as only 12.9% of the total observed variation was partitioned between major geographical regions.
[Show abstract][Hide abstract] ABSTRACT: The extent of linkage disequilibrium (LD) between molecular markers impacts genome-wide association studies and implementation of genomic selection. The availability of high-density single nucleotide polymorphism (SNP) genotyping platforms makes it possible to investigate LD at an unprecedented resolution. In this work, we characterised LD decay in breeds of beef cattle of taurine, indicine and composite origins and explored its variation across autosomes and the X chromosome.
In each breed, LD decayed rapidly and r2 was less than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into three groups of similar LD decay that distinguished the three main cattle types. At short distances between markers (< 10 kb), taurine breeds showed higher LD (r2 = 0.45) than their indicine (r2 = 0.25) and composite (r2 = 0.32) counterparts. This higher LD in taurine breeds was attributed to a smaller effective population size and a stronger bottleneck during breed formation. Using all SNPs on only the X chromosome, the three cattle types could still be distinguished. However for taurine breeds, the LD decay on the X chromosome was much faster and the background level much lower than for indicine breeds and composite populations. When using only SNPs that were polymorphic in all breeds, the analysis of the X chromosome mimicked that of the autosomes.
The pattern of LD mirrored some aspects of the history of breed populations and showed a sharp decay with increasing physical distance between markers. We conclude that the availability of the HD chip can be used to detect association signals that remained hidden when using lower density genotyping platforms, since LD dropped below 0.2 at distances of 50 kb.
[Show abstract][Hide abstract] ABSTRACT: Genomic information allows population relatedness to be inferred and selected genes to be identified. Single nucleotide polymorphism microarray (SNP-chip) data, a proxy for genome composition, contains patterns in allele order and proportion. These patterns can be quantified by compression efficiency (CE). In principle, the composition of an entire genome can be represented by a CE number quantifying allele representation and order.
We applied a compression algorithm (DEFLATE) to genome-wide high-density SNP data from 4,155 human, 1,800 cattle, 1,222 sheep, 81 dogs and 49 mice samples. All human ethnic groups can be clustered by CE and the clusters recover phylogeography based on traditional fixation index (FST) analyses. CE analysis of other mammals results in segregation by breed or species, and is sensitive to admixture and past effective population size. This clustering is a consequence of individual patterns such as runs of homozygosity. Intriguingly, a related approach can also be used to identify genomic loci that show population-specific CE segregation. A high resolution CE 'sliding window' scan across the human genome, organised at the population level, revealed genes known to be under evolutionary pressure. These include SLC24A5 (European and Gujarati Indian skin pigmentation), HERC2 (European eye color), LCT (European and Maasai milk digestion) and EDAR (Asian hair thickness). We also identified a set of previously unidentified loci with high population-specific CE scores including the chromatin remodeler SCMH1 in Africans and EDA2R in Asians. Closer inspection reveals that these prioritised genomic regions do not correspond to simple runs of homozygosity but rather compositionally complex regions that are shared by many individuals of a given population. Unlike FST, CE analyses do not require ab initio population comparisons and are amenable to the hemizygous X chromosome.
We conclude with a discussion of the implications of CE for a complex systems science view of genome evolution. CE allows one to clearly visualise the evolution of individual genomes and populations through a formal, mathematically-rigorous information space. Overall, CE makes a set of biological predictions, some of which are unique and await functional validation.
[Show abstract][Hide abstract] ABSTRACT: DNA-based parentage determination accelerates genetic improvement in sheep by increasing pedigree accuracy. Single nucleotide polymorphism (SNP) markers can be used for determining parentage and to provide unique molecular identifiers for tracing sheep products to their source. However, the utility of a particular "parentage SNP" varies by breed depending on its minor allele frequency (MAF) and its sequence context. Our aims were to identify parentage SNPs with exceptional qualities for use in globally diverse breeds and to develop a subset for use in North American sheep. Starting with genotypes from 2,915 sheep and 74 breed groups provided by the International Sheep Genomics Consortium (ISGC), we analyzed 47,693 autosomal SNPs by multiple criteria and selected 163 with desirable properties for parentage testing. On average, each of the 163 SNPs was highly informative (MAF≥0.3) in 48±5 breed groups. Nearby polymorphisms that could otherwise confound genetic testing were identified by whole genome and Sanger sequencing of 166 sheep from 54 breed groups. A genetic test with 109 of the 163 parentage SNPs was developed for matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The scoring rates and accuracies for these 109 SNPs were greater than 99% in a panel of North American sheep. In a blinded set of 96 families (sire, dam, and non-identical twin lambs), each parent of every lamb was identified without using the other parent's genotype. In 74 ISGC breed groups, the median estimates for probability of a coincidental match between two animals (PI), and the fraction of potential adults excluded from parentage (PE) were 1.1×10(-39) and 0.999987, respectively, for the 109 SNPs combined. The availability of a well-characterized set of 163 parentage SNPs facilitates the development of high-throughput genetic technologies for implementing accurate and economical parentage testing and traceability in many of the world's sheep breeds.
PLoS ONE 01/2014; 9(4):e94851. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Europe, especially in Mediterranean areas, the sheep has been traditionally exploited as a dual purpose species, with income from both meat and milk. Modernization of husbandry methods and the establishment of breeding schemes focused on milk production have led to the development of "dairy breeds." This study investigated selective sweeps specifically related to dairy production in sheep by searching for regions commonly identified in different European dairy breeds. With this aim, genotypes from 44,545 SNP markers covering the sheep autosomes were analysed in both European dairy and non-dairy sheep breeds using two approaches: (i) identification of genomic regions showing extreme genetic differentiation between each dairy breed and a closely related non-dairy breed, and (ii) identification of regions with reduced variation (heterozygosity) in the dairy breeds using two methods. Regions detected in at least two breeds (breed pairs) by the two approaches (genetic differentiation and at least one of the heterozygosity-based analyses) were labeled as core candidate convergence regions and further investigated for candidate genes. Following this approach six regions were detected. For some of them, strong candidate genes have been proposed (e.g. ABCG2, SPP1), whereas some other genes designated as candidates based on their association with sheep and cattle dairy traits (e.g. LALBA, DGAT1A) were not associated with a detectable sweep signal. Few of the identified regions were coincident with QTL previously reported in sheep, although many of them corresponded to orthologous regions in cattle where QTL for dairy traits have been identified. Due to the limited number of QTL studies reported in sheep compared with cattle, the results illustrate the potential value of selection mapping to identify genomic regions associated with dairy traits in sheep.
PLoS ONE 01/2014; 9(5):e94623. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most published genomewide association studies (GWAS) in sheep have investigated recessively inherited monogenic traits. The objective here was to assess the feasibility of performing GWAS for a dominant trait for which the genetic basis was already known. A total of 42 Manchega and Rasa Aragonesa sheep that segregate solid black or white coat pigmentation were genotyped using the SNP50 BeadChip. Previous analysis in Manchegas demonstrated a complete association between the pigmentation trait and alleles of the MC1R gene, setting an a priori expectation for GWAS. Multiple methods were used to identify and quantify the strength of population substructure between black and white animals, before allelic association testing was performed for 49 034 SNPs. Following correction for substructure, GWAS identified the most strongly associated SNP (s26449) was also the closest to the MC1R gene. The finding was strongly supported by the permutation tree-based random forest (RF) analysis. Importantly, GWAS identified unlinked SNP with only slightly lower p-values than for s26449. Random forest analysis indicated these were false positives, suggesting interpretation based on both approaches was beneficial. The results indicate that a combined analytical approach can be successful in studies where a modest number of animals are available and substantial population stratification exists.
Journal of Animal Breeding and Genetics 12/2013; 130(6):468-75. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This work aimed to investigate the population history and patterns of genetic diversity present within the isolated population of New Zealand Arapawa sheep. In order to identify genetic regions associated with reversion to a feral lifestyle, a selection sweep analysis was performed comparing 40 Arapawas to related breeds using Wright’s fixation index (FST). Comparisons were graphed as the moving average of 5 FST values. A threshold of 0.25 was used to identify significant regions; 8 genomic regions were identified for the Arapawa and Florida Gulf Coast Native, 9 for the Arapawa and Castellana and 3 for the Arapawa and Australian Merino breed pair comparisons. One region on chromosome 2 was identified in all three comparisons with two underlying genes, CFDP2 and NAB1. Other genes identified were RXFP2, IFT88, SLC9A3, HERC2, NIPA1, NIPA2 and DACH2. The current work confirms Arapawa sheep are an important reservoir of unique gene variants available to the New Zealand sheep industry.
Association for the Advancement of Animal Breeding and Genetics, Napier, New Zealand; 10/2013
[Show abstract][Hide abstract] ABSTRACT: When domesticated species are not reproductively isolated from their wild relatives, the opportunity arises for artificially selected variants to be re-introduced into the wild. However, the evolutionary consequences of introgression of domesticated genes back into the wild are poorly understood. By combining high-throughput genotyping with 25 years of long-term ecological field data, we describe the occurrence and consequences of admixture between a primitive sheep breed, the free-living Soay sheep of St Kilda, and more modern breeds. Utilizing data from a 50 K ovine SNP chip, together with forward simulations of demographic scenarios, we show that admixture occurred between Soay sheep and a more modern breed, consistent with historical accounts, approximately 150 years ago. Haplotype-sharing analyses with other breeds revealed that polymorphisms in coat colour and pattern in Soay sheep arose as a result of introgression of genetic variants favoured by artificial selection. Because the haplotypes carrying the causative mutations are known to be under natural selection in free-living Soay sheep, the admixture event created an opportunity to observe the outcome of a 'natural laboratory' experiment where ancestral and domesticated genes competed with each other. The haplotype carrying the domesticated light coat colour allele was favoured by natural selection, while the haplotype associated with the domesticated self coat pattern allele was associated with decreased survival. Therefore, we demonstrate that introgression of domesticated alleles into wild populations can provide a novel source of variation capable of generating rapid evolutionary changes.
[Show abstract][Hide abstract] ABSTRACT: Modern livestock breeding practices provide new opportunities for producing animals that are adapted to their production environment and are free of disease. Using current knowledge of biology and by seeking 'the desired outcome' animal selection strategies can be designed that deliver more precisely defined results so maximising genetic gain and minimising risk. This review briefly describes the evolution of genetic selection in livestock and considers some of the positive and negative aspects of selection practices over time. The selection of sheep to withstand gastro-intestinal nematode parasitism is used as an example to explain how developments in selection strategy have improved genetic progress for complex traits. Re-evaluation of the understanding of the outcomes of selection for parasite resistance is used here to examine whether a more sophisticated approach is desirable, and to propose a number of additional phenotype measurement strategies that could complement and improve the quality of information used for animal selection. Finally some ideas are presented for creating a situation where a designed, highly defined breeding objective might be used to increase precision and reduce risk. This may become possible via research to adapt or develop tools for more sophisticated phenotypic evaluation, to discover biological processes integral to desired breed changes, and to define desired animal types which match economic and societal expectations.
The Veterinary Journal 05/2013; · 2.42 Impact Factor