Copy number variants in the sheep genome detected using multiple approaches.
Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs.



In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %).



This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs.
AbacusBio Limited, 442 Moray Place, PO Box 5585, Dunedin, 9058, New Zealand. gjenkins@abacusbio.co.nz.
Gemma M
GM
Jenkins
Victorian Department of Economic Development, Jobs, Transport and Resources, Bundoora, VIC, 3083, Australia.
Michael E
ME
Goddard
Department of Biochemistry, University of Otago, 710 Cumberland St, Dunedin, 9054, New Zealand.
Michael A
MA
Black
AgResearch, Invermay Agricultural Centre, PB 50034, Mosgiel, 9053, New Zealand.
Rudiger
R
Brauning
Department of Biochemistry, University of Otago, 710 Cumberland St, Dunedin, 9054, New Zealand.
Benoit
B
Auvray
AgResearch, Invermay Agricultural Centre, PB 50034, Mosgiel, 9053, New Zealand.
Ken G
KG
Dodds
CSIRO Animal, Food and Health Sciences, Queensland Bioscience Precinct, 306 Carmody Road, St Lucia, QLD 4067, Australia.
James W
JW
Kijas
Utah State University, 1435 Old Main Hill, Logan, UT, 84322-1435-1435, USA.
Noelle
N
Cockett
AgResearch, Invermay Agricultural Centre, PB 50034, Mosgiel, 9053, New Zealand.
John C
JC
McEwan
D000818:Animals; D033481:Chromosomes, Mammalian; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D016678:Genome; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012756:Sheep / Q000235:genetics*
Array CGH; Copy number variants; SNP; Sequence; Sheep