A genome-wide survey reveals a deletion polymorphism associated with resistance to gastrointestinal nematodes in Angus cattle
- 528 Downloads
Gastrointestinal (GI) nematode infections are a worldwide threat to human health and animal production. In this study, we performed a genome-wide association study between copy number variations (CNVs) and resistance to GI nematodes in an Angus cattle population. Using a linear regression analysis, we identified one deletion CNV which reaches genome-wide significance after Bonferroni correction. With multiple mapped human olfactory receptor genes but no annotated bovine genes in the region, this significantly associated CNV displays high population frequencies (58.26 %) with a length of 104.8 kb on chr7. We further investigated the linkage disequilibrium (LD) relationships between this CNV and its nearby single nucleotide polymorphisms (SNPs) and genes. The underlining haplotype blocks contain immune-related genes such as ZNF496 and NLRP3. As this CNV co-segregates with linked SNPs and associated genes, we suspect that it could contribute to the detected variations in gene expression and thus differences in host parasite resistance.
KeywordsCopy number variation (CNV) Gastrointestinal nematodes Association
Copy number variation
Single nucleotide polymorphism
We thank Reuben Anderson and Alexandre Dimitriv for their technical assistance. This work was supported in part by AFRI grant no. 2011-67015-30183 from USDA NIFA. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer.
Conflict of interest
The authors declare that they have no competing interests.
- Araujo RN, Padilha T, Zarlenga D, Sonstegard T, Connor EE, Van Tassel C, Lima WS, Nascimento E, Gasbarre LC (2009) Use of a candidate gene array to delineate gene expression patterns in cattle selected for resistance or susceptibility to intestinal nematodes. Vet Parasitol 162:106–115PubMedCrossRefGoogle Scholar
- Bickhart DM, Hou Y, Schroeder SG, Alkan C, Cardone MF, Matukumalli LK, Song J, Schnabel RD, Ventura M, Taylor JF, Garcia JF, Van Tassell CP, Sonstegard TS, Eichler EE, Liu GE (2012) Copy number variation of individual cattle genomes using next-generation sequencing. Genome Res 22:778–790PubMedCrossRefPubMedCentralGoogle Scholar
- Crawford AM, Paterson KA, Dodds KG, Diez TC, Williamson PA, Roberts TM, Bisset SA, Beattie AE, Greer GJ, Green RS, Wheeler R, Shaw RJ, Knowler K, McEwan JC (2006) Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees. BMC Genomics 7:178PubMedCrossRefPubMedCentralGoogle Scholar
- Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225–2229PubMedCrossRefGoogle Scholar
- Harhay GP, Smith TP, Alexander LJ, Haudenschild CD, Keele JW, Matukumalli LK, Schroeder SG, Van Tassell CP, Gresham CR, Bridges SM, Burgess SC, Sonstegard TS (2010) An atlas of bovine gene expression reveals novel distinctive tissue characteristics and evidence for improving genome annotation. Genome Biol 11:R102PubMedCrossRefPubMedCentralGoogle Scholar
- Hou Y, Liu GE, Bickhart DM, Matukumalli LK, Li C, Song J, Gasberre LC, Van Tassell CP, Sonstegard TS (2011b) Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus cattle. Funct Integr Genomics 12:81–92PubMedCrossRefGoogle Scholar
- Hou Y, Bickhart DM, Hvinden ML, Li C, Song J, Boichard DA, Fritz S, Eggen A, Denise S, Wiggans GR, Sonstegard TS, Van Tassell CP, Liu GE (2012) Fine mapping of copy number variations on two cattle genome assemblies using high density SNP array. BMC Genomics 13:376PubMedCrossRefPubMedCentralGoogle Scholar
- Kim E, Sonstegard TS, Silva MVGB, Gasbarre LC, Van Tassell CP (2013) Identification of QTL affecting gastrointestinal nematodes resistance in an experimental Angus population. Animal Genetics AcceptedGoogle Scholar
- 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 (2010) Analysis of copy number variations among diverse cattle breeds. Genome Res 20:693–703PubMedCrossRefPubMedCentralGoogle Scholar
- Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N, Redon R, Bird CP, de Grassi A, Lee C, Tyler-Smith C, Carter N, Scherer SW, Tavare S, Deloukas P, Hurles ME, Dermitzakis ET (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315:848–853PubMedCrossRefPubMedCentralGoogle Scholar