Copy number variation of individual cattle genomes using next-generation sequencing

Bickhart, D.M.
Hou, Y.
Schroeder, S.G.
Alkan C.
Cardone, M.F.
Matukumalli L.K.
Song J.
Schnabel, R.D.
Ventura M.
Taylor J.F.
Source Title
Genome Research
Print ISSN
Electronic ISSN
778 - 790
Journal Title
Journal ISSN
Volume Title

Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome - wide copy number differences among five taurine (three Angus, one Holstein, and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1265 CNV regions comprising ∼55.6-Mbp sequence-476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with array comparative genomic hybridization (aCGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH), achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (∼52%, χ 2 test; P-value <0.05). In contrast, genes related to pathogen- and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and WC1, suggesting that some CNVs may be associated with breed-specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome-wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome. © 2012 by Cold Spring Harbor Laboratory Press.

Other identifiers
Book Title
apolipoprotein, fatty acid binding protein 2, taurine, adaptation, article, beef cattle, breeding, cattle, chromosome map, comparative genomic hybridization, copy number variation, fluorescence in situ hybridization, gene duplication, gene sequence, genome analysis, lipid metabolism, lipid transport, molecular genetics, nonhuman, nucleotide sequence, pedigree analysis, polymerase chain reaction, priority journal, promoter region, quantitative analysis, quantitative trait locus, sequence analysis, Animals, Cattle, Chromosome Mapping, Chromosomes, Mammalian, Comparative Genomic Hybridization, DNA Copy Number Variations, Fatty Acid-Binding Proteins, Female, Gene Dosage, Gene Duplication, Genome, Genomics, In Situ Hybridization, Fluorescence, Male, Polymerase Chain Reaction, Sequence Analysis, DNA, Species Specificity, Bos
Published Version (Please cite this version)