title: Analysis of copy number variations among diverse cattle breeds.
abstract: Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or approximately 1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.
authors.affiliation: USDA-ARS, ANRI, Bovine Functional Genomics Laboratory, Beltsville, Maryland 20705, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Liu
authors.forename: Yali
authors.initials: Y
authors.lastname: Hou
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Cardone
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Angelo
authors.initials: A
authors.lastname: Cellamare
authors.forename: Apratim
authors.initials: A
authors.lastname: Mitra
authors.forename: Leeson J
authors.initials: LJ
authors.lastname: Alexander
authors.forename: Luiz L
authors.initials: LL
authors.lastname: Coutinho
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Dell'Aquila
authors.forename: Lou C
authors.initials: LC
authors.lastname: Gasbarre
authors.forename: Gianni
authors.initials: G
authors.lastname: Lacalandra
authors.forename: Robert W
authors.initials: RW
authors.lastname: Li
authors.forename: Lakshmi K
authors.initials: LK
authors.lastname: Matukumalli
authors.forename: Dan
authors.initials: D
authors.lastname: Nonneman
authors.forename: Luciana C de A
authors.initials: LC
authors.lastname: Regitano
authors.forename: Tim P L
authors.initials: TP
authors.lastname: Smith
authors.forename: Jiuzhou
authors.initials: J
authors.lastname: Song
authors.forename: Tad S
authors.initials: TS
authors.lastname: Sonstegard
authors.forename: Curt P
authors.initials: CP
authors.lastname: Van Tassell
authors.forename: Mario
authors.initials: M
authors.lastname: Ventura
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Tara G
authors.initials: TG
authors.lastname: McDaneld
authors.forename: John W
authors.initials: JW
authors.lastname: Keele
mesh_terms: D000818:Animals; D001947:Breeding; D002417:Cattle / Q000145:classification* / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D018628:Gene Dosage; D005828:Genetics, Population; D016678:Genome; D056914:Genomic Structural Variation; D023281:Genomics; D017404:In Situ Hybridization, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D056916:Segmental Duplications, Genomic; D013045:Species Specificity