Home LiteratureArticle Details
PMID: 20212021 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Analysis of copy number variations among diverse cattle breeds.

Genome research ·Vol. 20 ·No. 5 ·2010-05-00 ·Pages 693-703

Liu GE, Hou Y, Zhu B, Cardone MF, Jiang L, Cellamare A, Mitra A, Alexander LJ, Coutinho LL, Dell'Aquila ME, Gasbarre LC, Lacalandra G, Li RW, Matukumalli LK, Nonneman D, Regitano LC, Smith TP, Song J, Sonstegard TS, Van Tassell CP, Ventura M, Eichler EE, McDaneld TG, Keele JW

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.

MeSH Terms
Animals Breeding Cattle/classification,genetics Comparative Genomic Hybridization DNA Copy Number Variations Gene Dosage Genetics, Population Genome Genomic Structural Variation Genomics In Situ Hybridization, Fluorescence Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction/methods Segmental Duplications, Genomic Species Specificity
Authors & Affiliations
24 authors, click to expand affiliations / ORCID
Liu George E
USDA-ARS, ANRI, Bovine Functional Genomics Laboratory, Beltsville, Maryland 20705, USA.
Hou Yali
Zhu Bin
Cardone Maria Francesca
Jiang Lu
Cellamare Angelo
Mitra Apratim
Alexander Leeson J
Coutinho Luiz L
Dell'Aquila Maria Elena
Gasbarre Lou C
Lacalandra Gianni
Li Robert W
Matukumalli Lakshmi K
Nonneman Dan
Regitano Luciana C de A
Smith Tim P L
Song Jiuzhou
Sonstegard Tad S
Van Tassell Curt P
Ventura Mario
Eichler Evan E
McDaneld Tara G
Keele John W
References (83)
83 references, click to expand
  1. Significant gene content variation characterizes the genomes of inbred mouse strains.
    Genome Res. 2007 Dec;17(12):1743-54 PMID: 17989247
  2. Genomic copy number and expression variation within the C57BL/6J inbred mouse strain.
    Genome Res. 2008 Jan;18(1):60-6 PMID: 18032724
  3. A physical map of the bovine genome.
    Genome Biol. 2007;8(8):R165 PMID: 17697342
  4. SNP discovery and allele frequency estimation by deep sequencing of reduced representation libraries.
    Nat Methods. 2008 Mar;5(3):247-52 PMID: 18297082
  5. Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies.
    Hum Mol Genet. 2008 Apr 15;17(8):1127-36 PMID: 18180252
  6. Distribution and functional impact of DNA copy number variation in the rat.
    Nat Genet. 2008 May;40(5):538-45 PMID: 18443591
  7. Nonrecurrent MECP2 duplications mediated by genomic architecture-driven DNA breaks and break-induced replication repair.
    Genome Res. 2008 Jun;18(6):847-58 PMID: 18385275
  8. Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster.
    Science. 2008 Jun 20;320(5883):1629-31 PMID: 18535209
  9. Mouse segmental duplication and copy number variation.
    Nat Genet. 2008 Jul;40(7):909-14 PMID: 18500340
  10. Detection of germline and somatic copy number variations in cattle.
    Dev Biol (Basel). 2008;132:231-7 PMID: 18817307
  11. Extending genome-wide association studies to copy-number variation.
    Hum Mol Genet. 2008 Oct 15;17(R2):R135-42 PMID: 18852202
  12. Copy-number variations associated with neuropsychiatric conditions.
    Nature. 2008 Oct 16;455(7215):919-23 PMID: 18923514
  13. Copy number variation and evolution in humans and chimpanzees.
    Genome Res. 2008 Nov;18(11):1698-710 PMID: 18775914
  14. Characterization of a novel microdeletion polymorphism on BTA5 in cattle.
    Anim Genet. 2008 Dec;39(6):655-8 PMID: 18699832
  15. Analysis of copy number variants and segmental duplications in the human genome: Evidence for a change in the process of formation in recent evolutionary history.
    Genome Res. 2008 Dec;18(12):1865-74 PMID: 18842824
  16. Mapping DNA structural variation in dogs.
    Genome Res. 2009 Mar;19(3):500-9 PMID: 19015322
  17. The genomic architecture of segmental duplications and associated copy number variants in dogs.
    Genome Res. 2009 Mar;19(3):491-9 PMID: 19129542
  18. Copy number variants, diseases and gene expression.
    Hum Mol Genet. 2009 Apr 15;18(R1):R1-8 PMID: 19297395
  19. Comparative map alignment of BTA27 and HSA4 and 8 to identify conserved segments of genome containing fat deposition QTL.
    Mamm Genome. 2000 Aug;11(8):682-8 PMID: 10920240
  20. High resolution discovery and confirmation of copy number variants in 90 Yoruba Nigerians.
    Genome Biol. 2009;10(11):R125 PMID: 19900272
  21. Large, rare chromosomal deletions associated with severe early-onset obesity.
    Nature. 2010 Feb 4;463(7281):666-70 PMID: 19966786
  22. Origins and functional impact of copy number variation in the human genome.
    Nature. 2010 Apr 1;464(7289):704-12 PMID: 19812545
  23. The impact of copy number variation on local gene expression in mouse hematopoietic stem and progenitor cells.
    Nat Genet. 2009 Apr;41(4):430-7 PMID: 19270704
  24. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility.
    Science. 2005 Mar 4;307(5714):1434-40 PMID: 15637236
  25. Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains.
    Nat Genet. 2005 May;37(5):532-6 PMID: 15852006
  26. Segmental duplications and copy-number variation in the human genome.
    Am J Hum Genet. 2005 Jul;77(1):78-88 PMID: 15918152
  27. Fine-scale structural variation of the human genome.
    Nat Genet. 2005 Jul;37(7):727-32 PMID: 15895083
  28. Analysis of chromosome breakpoints in neuroblastoma at sub-kilobase resolution using fine-tiling oligonucleotide array CGH.
    Genes Chromosomes Cancer. 2005 Nov;44(3):305-19 PMID: 16075461
  29. Concerted and birth-and-death evolution of multigene families.
    Annu Rev Genet. 2005;39:121-52 PMID: 16285855
  30. Mechanisms of change in gene copy number.
    Nat Rev Genet. 2009 Aug;10(8):551-64 PMID: 19597530
  31. Common variants conferring risk of schizophrenia.
    Nature. 2009 Aug 6;460(7256):744-7 PMID: 19571808
  32. Common variants on chromosome 6p22.1 are associated with schizophrenia.
    Nature. 2009 Aug 6;460(7256):753-7 PMID: 19571809
  33. Characterization and distribution of retrotransposons and simple sequence repeats in the bovine genome.
    Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12855-60 PMID: 19625614
  34. The genome response to artificial selection: a case study in dairy cattle.
    PLoS One. 2009;4(8):e6595 PMID: 19672461
  35. Copy number variation in human health, disease, and evolution.
    Annu Rev Genomics Hum Genet. 2009;10:451-81 PMID: 19715442
  36. Large-scale copy number polymorphism in the human genome.
    Science. 2004 Jul 23;305(5683):525-8 PMID: 15273396
  37. Detection of large-scale variation in the human genome.
    Nat Genet. 2004 Sep;36(9):949-51 PMID: 15286789
  38. Genomic segmental polymorphisms in inbred mouse strains.
    Nat Genet. 2004 Sep;36(9):952-4 PMID: 15322544
  39. Circular binary segmentation for the analysis of array-based DNA copy number data.
    Biostatistics. 2004 Oct;5(4):557-72 PMID: 15475419
  40. Mapping segmental and sequence variations among laboratory mice using BAC array CGH.
    Genome Res. 2005 Feb;15(2):302-11 PMID: 15687294
  41. A high-resolution survey of deletion polymorphism in the human genome.
    Nat Genet. 2006 Jan;38(1):75-81 PMID: 16327808
  42. Common deletions and SNPs are in linkage disequilibrium in the human genome.
    Nat Genet. 2006 Jan;38(1):82-5 PMID: 16327809
  43. Widening the spectrum of human genetic variation.
    Nat Genet. 2006 Jan;38(1):9-11 PMID: 16380720
  44. Structural variation in the human genome.
    Nat Rev Genet. 2006 Feb;7(2):85-97 PMID: 16418744
  45. Common deletion polymorphisms in the human genome.
    Nat Genet. 2006 Jan;38(1):86-92 PMID: 16468122
  46. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans.
    Nature. 2006 Feb 16;439(7078):851-5 PMID: 16482158
  47. Hotspots for copy number variation in chimpanzees and humans.
    Proc Natl Acad Sci U S A. 2006 May 23;103(21):8006-11 PMID: 16702545
  48. Complex patterns of copy number variation at sites of segmental duplications: an important category of structural variation in the human genome.
    Hum Genet. 2006 Sep;120(2):270-84 PMID: 16838144
  49. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon.
    Am J Hum Genet. 2006 Sep;79(3):439-48 PMID: 16909382
  50. Genomic organization and evolution of the ULBP genes in cattle.
    BMC Genomics. 2006;7:227 PMID: 16953885
  51. Global variation in copy number in the human genome.
    Nature. 2006 Nov 23;444(7118):444-54 PMID: 17122850
  52. Hereditary pancreatitis caused by triplication of the trypsinogen locus.
    Nat Genet. 2006 Dec;38(12):1372-4 PMID: 17072318
  53. A deletion of the paracellin-1 gene is responsible for renal tubular dysplasia in cattle.
    Genomics. 2000 Sep 15;68(3):229-36 PMID: 10995564
  54. Genetic evidence for Near-Eastern origins of European cattle.
    Nature. 2001 Apr 26;410(6832):1088-91 PMID: 11323670
  55. Segmental duplications: an 'expanding' role in genomic instability and disease.
    Nat Rev Genet. 2001 Oct;2(10):791-800 PMID: 11584295
  56. Partial deletion of the bovine ED1 gene causes anhidrotic ectodermal dysplasia in cattle.
    Genome Res. 2001 Oct;11(10):1699-705 PMID: 11591646
  57. Neocentromeres in 15q24-26 map to duplicons which flanked an ancestral centromere in 15q25.
    Genome Res. 2003 Sep;13(9):2059-68 PMID: 12915487
  58. An Alu transposition model for the origin and expansion of human segmental duplications.
    Am J Hum Genet. 2003 Oct;73(4):823-34 PMID: 14505274
  59. Segmental copy number variation shapes tissue transcriptomes.
    Nat Genet. 2009 Apr;41(4):424-9 PMID: 19270705
  60. Development and characterization of a high density SNP genotyping assay for cattle.
    PLoS One. 2009;4(4):e5350 PMID: 19390634
  61. The genome sequence of taurine cattle: a window to ruminant biology and evolution.
    Science. 2009 Apr 24;324(5926):522-8 PMID: 19390049
  62. Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds.
    Science. 2009 Apr 24;324(5926):528-32 PMID: 19390050
  63. Breakpoint regions and homologous synteny blocks in chromosomes have different evolutionary histories.
    Genome Res. 2009 May;19(5):770-7 PMID: 19342477
  64. Genomic organization and classification of the bovine WC1 genes and expression by peripheral blood gamma delta T cells.
    BMC Genomics. 2009;10:191 PMID: 19393067
  65. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.
    Nature. 2009 May 28;459(7246):569-73 PMID: 19404257
  66. A whole-genome assembly of the domestic cow, Bos taurus.
    Genome Biol. 2009;10(4):R42 PMID: 19393038
  67. Copy number variation at 1q21.1 associated with neuroblastoma.
    Nature. 2009 Jun 18;459(7249):987-91 PMID: 19536264
  68. Finding the missing heritability of complex diseases.
    Nature. 2009 Oct 8;461(7265):747-53 PMID: 19812666
  69. The origins and impact of primate segmental duplications.
    Trends Genet. 2009 Oct;25(10):443-54 PMID: 19796838
  70. The role of copy number variation in susceptibility to amyotrophic lateral sclerosis: genome-wide association study and comparison with published loci.
    PLoS One. 2009;4(12):e8175 PMID: 19997636
  71. Analysis of recent segmental duplications in the bovine genome.
    BMC Genomics. 2009;10:571 PMID: 19951423
  72. A comprehensive analysis of common copy-number variations in the human genome.
    Am J Hum Genet. 2007 Jan;80(1):91-104 PMID: 17160897
  73. Relative impact of nucleotide and copy number variation on gene expression phenotypes.
    Science. 2007 Feb 9;315(5813):848-53 PMID: 17289997
  74. Strong association of de novo copy number mutations with autism.
    Science. 2007 Apr 20;316(5823):445-9 PMID: 17363630
  75. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans.
    Am J Hum Genet. 2007 Jun;80(6):1037-54 PMID: 17503323
  76. A high-resolution map of segmental DNA copy number variation in the mouse genome.
    PLoS Genet. 2007 Jan 5;3(1):e3 PMID: 17206864
  77. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity.
    Nat Genet. 2007 Jun;39(6):721-3 PMID: 17529978
  78. Copy-number variation and association studies of human disease.
    Nat Genet. 2007 Jul;39(7 Suppl):S37-42 PMID: 17597780
  79. Copy number variants and genetic traits: closer to the resolution of phenotypic to genotypic variability.
    Nat Rev Genet. 2007 Aug;8(8):639-46 PMID: 17637735
  80. Gene duplication: a drive for phenotypic diversity and cause of human disease.
    Annu Rev Genomics Hum Genet. 2007;8:17-35 PMID: 17386002
  81. Paired-end mapping reveals extensive structural variation in the human genome.
    Science. 2007 Oct 19;318(5849):420-6 PMID: 17901297
  82. Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies.
    PLoS Genet. 2007 Oct;3(10):1787-99 PMID: 17953491
  83. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data.
    Genome Res. 2007 Nov;17(11):1665-74 PMID: 17921354
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1549-5469
DOI
10.1101/gr.105403.110
Published
2010-05-00
Epub
2010-00-08
Pages
693-703
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC2860171
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058815 · United States
NIGMS NIH HHS · GM058815 · United States
Databases
GEO
GSE19866
External Links
PubMed source DOI: 10.1101/gr.105403.110 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2