James W Kijas

Pfizer Animal Health Australia, Sydney, New South Wales, Australia

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Publications (84)279.07 Total impact

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    ABSTRACT: Phenotypic variability in horn characteristics, such as their size, number and shape, offers the opportunity to elucidate the molecular basis of horn development. The objective of this study was to map the genetic determinant controlling the production of four horns in two breeds, Jacob sheep and Navajo-Churro, and examine whether an eyelid abnormality occurring in the same populations is related. Genome-wide association mapping was performed using 125 animals from the two breeds that contain two- and four-horned individuals. A case-control design analysis of 570 712 SNPs genotyped with the ovine HD SNP Beadchip revealed a strong association signal on sheep chromosome 2. The 10 most strongly associated SNPs were all located in a region spanning Mb positions 131.9-132.6, indicating the genetic architecture underpinning the production of four horns is likely to involve a single gene. The closest genes to the most strongly associated marker (OAR2_132568092) were MTX2 and the HOXD cluster, located approximately 93 Kb and 251 Kb upstream respectively. The occurrence of an eyelid malformation across both breeds was restricted to polled animals and those carrying more than two horns. This suggests the eyelid abnormality may be associated with departures from the normal developmental production of two-horned animals and that the two conditions are developmentally linked. This study demonstrated the presence of separate loci responsible for the polled and four-horned phenotypes in sheep and advanced our understanding of the complexity that underpins horn morphology in ruminants.
    No preview · Article · Jan 2016 · Animal Genetics
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    ABSTRACT: Genetic relatedness is currently estimated by a combination of traditional pedigree-based approaches (i.e. numerator relationship matrices, NRM) and, given the recent availability of molecular information, using marker genotypes (via genomic relationship matrices, GRM). To date, GRM are computed by genome-wide pair-wise SNP (single nucleotide polymorphism) correlations. We describe a new estimate of genetic relatedness using the concept of normalised compression distance (NCD) that is borrowed from Information Theory. Analogous to GRM, the resultant compression relationship matrix (CRM) exploits numerical patterns in genome-wide allele order and proportion, which are known to vary systematically with relatedness. We explored properties of the CRM in two industry cattle datasets by analysing the genetic basis of yearling weight, a phenotype of moderate heritability. In both Brahman (Bos indicus) and Tropical Composite (Bos taurus by Bos indicus) populations, the clustering inferred by NCD was comparable to that based on SNP correlations using standard principal component analysis approaches. One of the versions of the CRM modestly increased the amount of explained genetic variance, slightly reduced the ‘missing heritability’ and tended to improve the prediction accuracy of breeding values in both populations when compared to both NRM and GRM. Finally, a sliding window-based application of the compression approach on these populations identified genomic regions influenced by introgression of taurine haplotypes. For these two bovine populations, CRM reduced the missing heritability and increased the amount of explained genetic variation for a moderately heritable complex trait. Given that NCD can sensitively discriminate closely related individuals, we foresee CRM having possible value for estimating breeding values in highly inbred populations.
    Preview · Article · Oct 2015 · Genetics Selection Evolution
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    ABSTRACT: The identification of genes influencing fitness is central to our understanding of the genetic basis of adaptation and how it shapes phenotypic variation in wild populations. Here, we used whole genome resequencing of wild Rocky Mountain bighorn sheep (Ovis canadensis) to > 50 fold coverage to identify 2.8 million SNPs and genomic regions bearing signatures of directional selection (i.e., selective sweeps). A comparison of SNP diversity between the X chromosome and the autosomes indicated that bighorn males had a dramatically reduced long term effective population size compared to females. This likely reflects a long history of intense sexual selection mediated by male-male competition for mates. Selective sweep scans based on heterozygosity and nucleotide diversity revealed evidence for a selective sweep shared across multiple populations at RXFP2, a gene that strongly affects horn size in domestic ungulates. The massive horns carried by bighorn rams appear to have evolved in part via strong positive selection at RXFP2. We identified evidence for selection within individual populations at genes affecting early body growth and cellular response to hypoxia; however these must be interpreted more cautiously as genetic drift is strong within local populations and may have caused false positives. These results represent a rare example of strong genomic signatures of selection identified at genes with known function in wild populations of a non-model species. Our results also showcase the value of reference genome assemblies from agricultural or model species for studies of the genomic basis of adaptation in closely related wild taxa. This article is protected by copyright. All rights reserved.
    Full-text · Article · Oct 2015 · Molecular Ecology
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    ABSTRACT: The last five years has witnessed the completion of reference genome projects for each of the major livestock species, along with the application of high throughput SNP genotyping to fast track gene discovery and genomic prediction. This paper explores one possible new direction in genomics and its possible impact on animal science. An international project has been initiated that aims to identify the genomic regions responsible for gene regulation, thereby providing functional annotation of animal genomes (FAANG). This seeks to increase our ability to interpret variation in genome sequence and predict the resulting phenotypic consequence. This has large implications for animal science and in particular animal breeding, given a key objective of genomic prediction is to use molecular data (currently SNP) to predict genetic merit. To successfully annotate the regulatory elements in genomic sequence, the FAANG Consortium has been created to provide coordination and standardisation in data collection, quality control and analysis. Aspects of the consortium are described, along with information on Australia's current and future contributions.
    Full-text · Conference Paper · Sep 2015
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    ABSTRACT: SNP chips are transforming animal breeding; low cost " assay-by-sequencing " methodologies and high quality reference genome sequences provide the opportunity for further significant improvement in both breeding and management. The Functional Annotation of ANimal Genomes (FAANG) consortium is applying methods developed by the human ENCODE project to annotate the genomes of livestock (sheep, cattle, pigs, etc.) with functional information including the probability that variation at a particular nucleotide has a causal role in any phenotype. We will contribute the detailed annotation of the transcriptome of the gastrointestinal tract of sheep to FAANG. We will undertake an integrated analysis of the variation in: genome sequence, transcription, gastrointestinal tract phenotypes and the environment across ~100 animals. This will be combined with analysis of a developmental time course of the gastrointestinal tract transcriptome from 30 days post conception to weaning, and an in-depth analysis of the gastrointestinal tract transcriptome from the new reference sheep, a North American Rambouillet. From this, and public FAANG data, we will estimate the probability that variation in a particular nucleotide has an impact on gastrointestinal phenotypes of interest (methane, nutrition, infection, microbial population) and identify the biological processes underlying the phenotype. This information will inform breeding schemes, identify management options and define phenotypes more precisely.
    Full-text · Conference Paper · Sep 2015
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    ABSTRACT: Merino and Merino-derived sheep breeds have been widely distributed across the world, both as purebred and admixed populations. They represent an economically and historically important genetic resource which over time has been used as the basis for the development of new breeds. In order to examine the genetic influence of Merino in the context of a global collection of domestic sheep breeds, we analyzed genotype data that were obtained with the OvineSNP50 BeadChip (Illumina) for 671 individuals from 37 populations, including a subset of breeds from the Sheep HapMap dataset. Based on a multi-dimensional scaling analysis, we highlighted four main clusters in this dataset, which corresponded to wild sheep, mouflon, primitive North European breeds and modern sheep (including Merino), respectively. The neighbor-network analysis further differentiated North-European and Mediterranean domestic breeds, with subclusters of Merino and Merino-derived breeds, other Spanish breeds and other Italian breeds. Model-based clustering, migration analysis and haplotype sharing indicated that genetic exchange occurred between archaic populations and also that a more recent Merino-mediated gene flow to several Merino-derived populations around the world took place. The close relationship between Spanish Merino and other Spanish breeds was consistent with an Iberian origin for the Merino breed, with possible earlier contributions from other Mediterranean stocks. The Merino populations from Australia, New Zealand and China were clearly separated from their European ancestors. We observed a genetic substructuring in the Spanish Merino population, which reflects recent herd management practices. Our data suggest that intensive gene flow, founder effects and geographic isolation are the main factors that determined the genetic makeup of current Merino and Merino-derived breeds. To explain how the current Merino and Merino-derived breeds were obtained, we propose a scenario that includes several consecutive migrations of sheep populations that may serve as working hypotheses for subsequent studies.
    Full-text · Article · Aug 2015 · Genetics Selection Evolution
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    ABSTRACT: Basic understanding of linkage disequilibrium (LD) and population structure, as well as the consistency of gametic phase across breeds is crucial for genome-wide association studies and successful implementation of genomic selection. However, it is still limited in goats. Therefore, the objectives of this research were: (i) to estimate genome-wide levels of LD in goat breeds using data generated with the Illumina Goat SNP50 BeadChip; (ii) to study the consistency of gametic phase across breeds in order to evaluate the possible use of a multi-breed training population for genomic selection and (iii) develop insights concerning the population history of goat breeds. Average r(2) between adjacent SNP pairs ranged from 0.28 to 0.11 for Boer and Rangeland populations. At the average distance between adjacent SNPs in the current 50 k SNP panel (~0.06 Mb), the breeds LaMancha, Nubian, Toggenburg and Boer exceeded or approached the level of linkage disequilibrium that is useful (r(2) > 0.2) for genomic predictions. In all breeds LD decayed rapidly with increasing inter-marker distance. The estimated correlations for all the breed pairs, except Canadian and Australian Boer populations, were lower than 0.70 for all marker distances greater than 0.02 Mb. These results are not high enough to encourage the pooling of breeds in a single training population for genomic selection. The admixture analysis shows that some breeds have distinct genotypes based on SNP50 genotypes, such as the Boer, Cashmere and Nubian populations. The other groups share higher genome proportions with each other, indicating higher admixture and a more diverse genetic composition. This work presents results of a diverse collection of breeds, which are of great interest for the implementation of genomic selection in goats. The LD results indicate that, with a large enough training population, genomic selection could potentially be implemented within breed with the current 50 k panel, but some breeds might benefit from a denser panel. For multi-breed genomic evaluation, a denser SNP panel also seems to be required.
    Full-text · Article · Jun 2015 · BMC Genetics
  • Y Jiang · X Wang · J W Kijas · B P Dalrymple
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    ABSTRACT: Domestic sheep (Ovis aries) can be divided into two groups with significantly different responses to hypoxic environments, determined by two allelic beta-globin haplotypes. Haplotype A is very similar to the goat beta-globin locus, whereas haplotype B has a deletion spanning four globin genes, including beta-C globin, which encodes a globin with high oxygen affinity. We surveyed the beta-globin locus using resequencing data from 70 domestic sheep from 42 worldwide breeds and three Ovis canadensis and two Ovis dalli individuals. Haplotype B has an allele frequency of 71.4% in O. aries and was homozygous (BB) in all five wild sheep. This shared ancestry indicates haplotype B is at least 2-3 million years old. Approximately 40 kb of the sequence flanking the ~37-kb haplotype B deletion had unexpectedly low identity between haplotypes A and B. Phylogenetic analysis showed that the divergent region of sheep haplotype B is remarkably distinct from the beta-globin loci in goat and cattle but still groups with the Ruminantia. We hypothesize that this divergent ~40-kb region in haplotype B may be from an unknown ancestral ruminant and was maintained in the lineage to O. aries, but not other Bovidae, evolving independently of haplotype A. Alternatively, the ~40-kb sequence in haplotype B was more recently acquired by an ancestor of sheep from an unknown non-Bovidae ruminant, replacing part of haplotype A. Haplotype B has a lower nucleotide diversity than does haplotype A, suggesting a recent bottleneck, whereas the higher frequency of haplotype B suggests a subsequent spread through the global population of O. aries. © 2015 Stichting International Foundation for Animal Genetics.
    No preview · Article · Jun 2015 · Animal Genetics
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    ABSTRACT: One of the most economically important areas within the Welsh agricultural sector is sheep farming, contributing around £230 million to the UK economy annually. Phenotypic selection over several centuries has generated a number of native sheep breeds, which are presumably adapted to the diverse and challenging landscape of Wales. Little is known about the history, genetic diversity and relationships of these breeds with other European breeds. We genotyped 353 individuals from 18 native Welsh sheep breeds using the Illumina OvineSNP50 array and characterised the genetic structure of these breeds. Our genotyping data were then combined with, and compared to, those from a set of 74 worldwide breeds, previously collected during the International Sheep Genome Consortium HapMap project. Model based clustering of the Welsh and European breeds indicated shared ancestry. This finding was supported by multidimensional scaling analysis (MDS), which revealed separation of the European, African and Asian breeds. As expected, the commercial Texel and Merino breeds appeared to have extensive co-ancestry with most European breeds. Consistently high levels of haplotype sharing were observed between native Welsh and other European breeds. The Welsh breeds did not, however, form a genetically homogeneous group, with pairwise F ST between breeds averaging 0.107 and ranging between 0.020 and 0.201. Four subpopulations were identified within the 18 native breeds, with high homogeneity observed amongst the majority of mountain breeds. Recent effective population sizes estimated from linkage disequilibrium ranged from 88 to 825. Welsh breeds are highly diverse with low to moderate effective population sizes and form at least four distinct genetic groups. Our data suggest common ancestry between the native Welsh and European breeds. These findings provide the basis for future genome-wide association studies and a first step towards developing genomics assisted breeding strategies in the UK.
    Full-text · Article · Jun 2015 · BMC Genetics
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    ABSTRACT: Background Domestic goats (Capra hircus) have been selected to play an essential role in agricultural production systems, since being domesticated from their wild progenitor, bezoar (Capra aegagrus). A detailed understanding of the genetic consequences imparted by the domestication process remains a key goal of evolutionary genomics. Results We constructed the reference genome of bezoar and sequenced representative breeds of domestic goats to search for genomic changes that likely have accompanied goat domestication and breed formation. Thirteen copy number variation genes associated with coat color were identified in domestic goats, among which ASIP gene duplication contributes to the generation of light coat-color phenotype in domestic goats. Analysis of rapidly evolving genes identified genic changes underlying behavior-related traits, immune response and production-related traits. Conclusion Based on the comparison studies of copy number variation genes and rapidly evolving genes between wild and domestic goat, our findings and methodology shed light on the genetic mechanism of animal domestication and will facilitate future goat breeding. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1606-1) contains supplementary material, which is available to authorized users.
    Full-text · Article · Jun 2015 · BMC Genomics
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    ABSTRACT: We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0622-4) contains supplementary material, which is available to authorized users.
    Full-text · Article · Mar 2015 · Genome biology
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    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.
    Full-text · Article · Dec 2014 · Molecular Biology and Evolution
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    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.
    No preview · Article · Nov 2014 · Molecular Ecology Resources
  • James W Kijas
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    ABSTRACT: Domestic animals represent an extremely useful model for linking genotypic and phenotypic variation. One approach involves identifying allele frequency differences between populations, using FST, to detect selective sweeps. While simple to calculate, FST may generate false positives due to aspects of population history. This prompted the development of hapFLK, a metric that measures haplotype differentiation while accounting for the genetic relationship between populations. The focus of this paper was to apply hapFLK in sheep with available SNP50 genotypes. The hapFLK approach identified a known selective sweep on chromosome 10 with high precision. Further, five regions were identified centered on genes with strong evidence for positive selection (COL1A2, NCAPG, LCORL, and RXFP2). Estimation of global FST revealed many more genomic regions, providing empirical data in support of published simulation-based results concerning elevated type I error associated with FST when it is being used to characterize sweep regions. The findings, while conducted using sheep SNP data, are likely to be applicable across those domestic animal species that have undergone artificial selection for desirable phenotypic traits.
    No preview · Article · Oct 2014 · Genome
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    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. Keywords: Random Forests GWAS
    No preview · Conference Paper · Aug 2014
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    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
    No preview · Conference Paper · Aug 2014
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    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
    No preview · Conference Paper · Aug 2014
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    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
    Full-text · Conference Paper · Aug 2014
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    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.
    Full-text · Conference Paper · Jul 2014
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    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.
    No preview · Article · Jul 2014 · Animal Genetics

Publication Stats

2k Citations
279.07 Total Impact Points

Institutions

  • 2013-2014
    • Pfizer Animal Health Australia
      Sydney, New South Wales, Australia
  • 2010-2013
    • The Commonwealth Scientific and Industrial Research Organisation
      • Division of Livestock Industries
      Canberra, Australian Capital Territory, Australia
    • University of Adelaide
      • School of Animal and Veterinary Sciences
      Tarndarnya, South Australia, Australia
  • 2006-2012
    • Meat & Livestock Australia
      Sydney, New South Wales, Australia
  • 2009
    • University of Alberta
      • Department of Biological Sciences
      Edmonton, Alberta, Canada
  • 2007
    • Adnan Menderes University
      • Department of Animal Science
      Güsel Hissar, Aydın, Turkey
  • 2002-2004
    • Cornell University
      • • College of Veterinary Medicine
      • • Baker Institute for Animal Health
      Ithaca, NY, United States