Genome-wide association (GWA) studies are being used in livestock, as in humans, to map genes affecting complex traits.
SNP panels for use in these GWA studies have recently become commercially available in cattle, dogs, sheep, chickens, pigs and horses.
GWA studies have successfully identified mutations causing single-gene traits, such as white spotting in dogs.
Associations for complex traits have been reported, but in most cases verification in independent studies has not yet occurred.
The SNP panels can be used in the selection of livestock even before they have been used to identify specific mutations causing variation in the economically important traits. This process is called genomic selection. It uses all the SNPs to estimate the genetic value of animals at a young age. By reducing the generation interval, the rate of genetic improvement can be doubled.
Genomic selection is already being implemented by dairy industries around the world, and other livestock industries are expected to follow in the near future.
Genome-wide panels of SNPs have recently been used in domestic animal species to map and identify genes for many traits and to select genetically desirable livestock. This has led to the discovery of the causal genes and mutations for several single-gene traits but not for complex traits. However, the genetic merit of animals can still be estimated by genomic selection, which uses genome-wide SNP panels as markers and statistical methods that capture the effects of large numbers of SNPs simultaneously. This approach is expected to double the rate of genetic improvement per year in many livestock systems.
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Meuwissen, T. H. E. & Goddard, M. E. The use of marker haplotypes in animal breeding schemes. Genet. Sel. Evol. 28, 161–176 (1996). Quantifies the benefits of MAS.
Falconer, D. S. & McKay, T. F. X. Introduction to Quantitative Genetics 4th edn (Longmans Green, UK, 1996).
Andersson, L. & Georges, M. Domestic animal genomics: deciphering the genetics of complex traits. Nature Rev. Genet. 5, 202–212 (2004).
Dekkers, J. C. M. & Hospital, F. Multifactorial genetics: the use of molecular genetics in the improvement of agricultural populations. Nature Rev. Genet. 3, 22–32 (2002).
Van Laere, A. S. et al. A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. Nature 425, 832–836 (2003).
Meuwissen, T. H. E., Hayes, B. J. & Goddard, M. E. Prediction of total genetic value using genome-wide dense marker maps. Genetics 157, 1819–1829 (2001). Introduced the concept and statistical methods for genomic selection.
Tolle, A. in Rep. VIth Int. Bloodgroup Congr. 40–52 (Inst. Blutgruppenforshung, Munich, Germany, 1959).
Neimann-Sorensen, A. & Robertson, A. The association between blood groups and several production characteristics in three Danish cattle breeds. Acta Agric. Scand. 11, 163–196 (1961).
Rendel, J. Relationships between blood groups and the fat percentage of the milk in cattle. Nature 189, 408–409 (1961).
Georges, M. et al. Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing. Genetics 139, 907–920 (1995).
Sved, J. A. Linkage disequilibrium and homozygosity of chromosome segments in finite populations. Theor. Popul. Biol. 2, 125–141 (1971).
Hayes, B. J. Visscher, P. M., McPartlan, H. & Goddard, M. E. A novel multilocus measure of linkage disequilibrium to estimate past effective population size. Genome Res. 13, 635–643 (2003).
Tenesa, A. et al. Recent human effective population size estimated from linkage disequilibrium. Genome Res. 17, 520–526 (2007).
De Roos, A. P. W., Hayes, B. J., Spelman, R. & Goddard, M. E. Linkage disequilibrium and persistence of phase in Holstein Friesian, Jersey and Angus cattle. Genetics 179, 1503–1512 (2008).
MacEachern, S., Hayes, B. J., McEwan, J. & Goddard, M. E. An examination of positive selection and changing effective population size in Angus and Holstein cattle populations (Bos taurus) using a high density SNP genotyping platform and the contribution of ancient polymorphism to genomic diversity in Domestic cattle. BMC Genomics 10, 181 (2009).
Sutter, N. B. et al. Extensive and breed-specific linkage disequilibrium in Canis familiaris. Genome Res. 14, 2388–2396 (2004).
Meuwissen, T. H. E. & Goddard, M. E. Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data. Genet. Sel. Evol. 36, 261–279 (2004).
Uleberg, E. et al. Fine mapping of a QTL for intramuscular fat on porcine chromosome 6 using combined linkage and linkage disequilibrium mapping. J. Anim. Breed Genet. 122, 1–6 (2005).
Gautier, M. et al. Fine mapping and physical characterization of two linked quantitative trait loci affecting milk fat yield in dairy cattle on BTA26. Genetics 172, 425–436 (2006).
Olsen, H. G., Meuwissen, T. H., Nilsen, H., Svendsen, M & Lien, S. Fine mapping of quantitative trait loci on bovine chromosome 6 affecting calving difficulty. J. Dairy Sci. 91, 4312–4322 (2008).
Tantia, M. S. et al. DGAT1 and ABCG2 polymorphism in Indian cattle (Bos indicus) and buffalo (Bubalus bubalis) breeds. BMC Vet. Res. 7, 32 (2006).
Barendse, W., Harrison, B. E., Bunch, R. J. & Thomas, M. B. Variation at the calpain 3 gene is associated with meat tenderness in zebu and composite breeds of cattle. BMC Genet. 9, 41 (2008).
Visscher, P. M. Sizing up human height variation. Nature Genet. 40, 489–490 (2008). Uses published results to demonstrate the small effect size of most QTLs.
Karlsson, E. K. et al. Efficient mapping of mendelian traits in dogs through genome-wide association. Nature Genet. 39, 1321–1328 (2007). Shows how mapping the same locus within two different breeds of dog can lead to discovery of a causal mutation.
Charlier, C. et al. Highly effective SNP-based association mapping and management of recessive defects in livestock. Nature Genet. 40, 449–454 (2008).
Kolbehdari, D. et al. A whole-genome scan to map quantitative trait loci for conformation and functional traits in Canadian Holstein bulls. J. Dairy Sci. 91, 2844–2856 (2008).
Daetwyler, H. D., Schenkel, F. S., Sargolzaei, M. & Robinson, J. A. A genome scan to detect quantitative trait loci for economically important traits in Holstein cattle using two methods and a dense single nucleotide polymorphism map. J. Dairy Sci. 91, 3225–3236 (2008).
Barendse, W. et al. A validated whole-genome association study of efficient food conversion in cattle. Genetics. 176, 1893–1905 (2007).
Lillehammer, M., Hayes, B. J., Meuwissen, T. H. E. & Goddard, M. E. Gene by environment interactions for production traits in Australian dairy cattle. J. Dairy Sci. (in the press).
Long, N., Gianola, D., Rosa, G. J., Weigel, K. A. & Avendaño, S. Marker-assisted assessment of genotype by environment interaction: a case study of single nucleotide polymorphism-mortality association in broilers in two hygiene environments. J. Anim. Sci. 86, 3358–3366 (2008).
Hasenstein, J. R., Hassen, A. T., Dekkers, J. C. & Lamont, S. J. High resolution, advanced intercross mapping of host resistance to Salmonella colonization. Dev. Biol. 132, 213–218 (2008).
Beavis, W. D. in Molecular Dissection of Complex Traits (ed. Patterson, A. H.) 145–162 (CRC, New York, 1998).
Sanna, S. et al. Common variants in the GDF5-UQCC region are associated with variation in human height. Nature Genet. 40, 198–203 (2008).
Franke, A. et al. Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nature Genet. 40, 713–715 (2008).
Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).
Jones, P. et al. Single-nucleotide-polymorphism-based association mapping of dog stereotypes. Genetics 179, 1033–1044 (2008).
Spelman, R. J. Ford, C. A., McElhinney, P., Gregory, G. C. & Snell, R. G. Characterization of the DGAT1 gene in the New Zealand dairy population. J. Dairy Sci. 85, 3514–3517 (2002).
Dunner, S. et al. Haplotype diversity of the myostatin gene among beef cattle breeds. Genet. Sel. Evol. 35, 103–118 (2003).
Smith, C. Improvement of metric traits through specific genetic loci. Anim. Prod. 9, 349–358 (1967).
Fujii, J. et al. Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Science 253, 448–451 (1991).
Piper, L., R., Bindon, B. M. & Davis, G. H. in Genetics of Reproduction in Sheep (eds Land, R. B. & Robinson D. W) 115–125 (Butterworths, London, 1985).
Shuster, D. E., Kehrli, M. E. Jr, Ackermann, M. R. & Gilbert, R. O. Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle. Proc. Natl Acad. Sci. USA 89, 9225–9229 (1982).
Goldman, W. N. et al. Two alleles of a neural protein gene linked to scrapie in sheep. Proc. Natl Acad. Sci. USA 87, 2476–2480 (1990).
Davis, G. H. Major genes affecting ovulation rate in sheep. Genet. Sel. Evol. 37 (Suppl. 1), S11–S23 (2005).
Van Arendonk, J. A. M. et al. in From Jay L. Lush to Genomics: Visions for Animal Breeding and Genetics (eds Dekkers, J. C. M., Lamont, S. J. & Rothschild, M. F.) 60–69 (Iowa State Univ., Ames, 1999).
Plastow, G. S. et al. in Proceedings 28th Annual Meeting National Swine Improvement Federation 151–154 (Iowa State Univ., Ames, 2003).
Dekkers, J. C. Commercial application of marker- and gene-assisted selection in livestock: strategies and lessons. J. Anim. Sci. 82, E313–E328 (2004).
Schaeffer, L. R. Strategy for applying genome-wide selection in dairy cattle. J. Anim. Breed. Genet. 123, 218–223 (2006). Calculates the gain in selection response from genomic selection in dairy cattle.
VanRaden, P. M. et al. Reliability of genomic predictions for North American Holstein bulls. J. Dairy Sci. 92, 16–24 (2009).
Harris, B. L., Johnson, D. L. & Spelman, R. J. in Proc. Interbull Meeting, Bulletin 39 (Niagara Falls, Canada, 2008).
Hayes, B. J., Bowman, P. J., Chamberlain, A. C. & Goddard, M. E. Genomic selection in dairy cattle: progress and challenges. J. Dairy Sci. 92, 433–443 (2008).
Legarra A., Robert-Granié, C., Manfredi, E. & Elsen, J. M. Performance of genomic selection in mice. Genetics. 180, 611–618 (2008).
Lee, S. H., van der Werf, J. H., Hayes, B. J., Goddard, M. E. & Visscher, P. M. Predicting unobserved phenotypes for complex traits from whole-genome SNP data. PLoS Genet. 4, e1000231 (2008).
González-Recio, O., Gianola, D., Rosa, G. J., Weigel, K. A., Kranis, A. Genome-assisted prediction of a quantitative trait measured in parents and progeny: application to food conversion rate in chickens. Genet. Sel. Evol. 41, 3 (2009).
Goddard, M. E. Genomic selection: prediction of accuracy and maximisation of long term response. Genetica 14 Aug 2008 (doi: 10.1007/s10709-008-9308-0). Presents formulae for the accuracy of genomic selection and the optimization of long-term selection response.
Goddard, M. E. & Hayes, B. J. Genomic selection. J. Anim. Breed. Genet. 124, 323–330 (2007).
Hayes, B. J., Visscher, P. M. & Goddard, M. E. Increased accuracy of selection by using the realised relationship matrix. Genet. Res. 91, 47–60 (2009).
Dalton, R. No bull: genes for better milk. Nature 457, 369 (2009).
Maher, B. The case of the missing heritability. Nature 456, 18–21 (2008).
Willer, C. J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature Genet. 41, 25–34 (2009).
Grisart, B. et al. Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition. Genome Res. 12, 222–231 (2002).
Hayes, B. J. & Goddard, M. E. The distribution of the effects of genes affecting quantitative traits in livestock. Genet. Sel. Evol. 33, 209–229 (2001).
Weller, J. I. Shlezinger, M. & Ron, M. Correcting for bias in estimation of quantitative trait loci effects. Genet. Sel. Evol. 37, 501–522 (2005).
Bellinge, R. H., Liberles, D. A., Iaschi, S. P., O'Brien, P. A. & Tay, G. K. Myostatin and its implications on animal breeding: a review. Anim. Genet. 36, 1–6 (2005).
Clop, A. et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nature Genet. 38, 813–818 (2006).
The Bovine HapMap Consortium. Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds. Science 324, 528–532 (2009).
Drögemüller, C. et al. A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321, 1462 (2008).
Awano, T. et al. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc. Natl Acad. Sci. USA 106, 2794–2799 (2009).
Wiik, A. C. et al. A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund. Genome Res. 18, 1415–1421 (2008).
Salmon Hillbertz, N. H. et al. Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs. Nature Genet. 39, 1318–1320 (2007).
The authors would like to thank H. Campbell and H. Burrow for cattle pictures used in this Review.
- Quantitative trait
A measurable trait that depends on the cumulative action of many genes and the environment, and that can vary among individuals over a given range to produce a continuous distribution of phenotypes.
- Estimated breeding value
An estimate of the additive genetic merit for a particular trait that an individual will pass on to its descendents.
The proportion of phenotypic variance caused by additive genetic variation.
- Genetic improvement
Deliberate genetic change in a population of domestic animals or plants brought about by human control of their selection and breeding that makes them more suitable for the purpose for which they are kept.
- Genomic selection
Selection of animals for breeding based on estimated breeding values calculated from the joint effects of genetic markers covering the whole genome.
- Linkage disequilibrium
The absence of linkage equilibrium so that the allele at one locus is correlated with the allele at another locus.
- Effective population size
The number of individuals in an idealized population with random mating and no selection that would lead to the same rate of inbreeding as observed in the real population. The effective population size can be much less than the actual population size owing to the unequal genetic contribution of individuals to the next generation.
- Linear model
A statistical model that assumes that the observed phenotypic value can be explained by the sum of the effects of independent variables and a random error, which is usually assumed to be normally distributed.
- Polygenic breeding value
The additive genetic merit an individual passes on to its descendents owing to the combined contribution of many genes of small effect, but possibly excluding some specified genes.
A population or sample of individuals derived from more than one race or breed and that have not undergone random mating.
- LD phase
If linkage disequilibrium (LD) exists between genes A and B, each with two alleles (A or a and B or b), then gametes that carry allele A can carry B or b. Thus, LD can exist in one of two phases: gametes that are more commonly AB and ab, or gametes that are more commonly Ab and aB.
- Beavis effect
The tendency for statistically significant effects to be overestimated when many effects are tested for significance.
- Minor allele frequency
The frequency of the less frequent allele in a two-allele polymorphism.
- Genomic breeding value
An estimate of an animal's genetic merit, including genomic information
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Goddard, M., Hayes, B. Mapping genes for complex traits in domestic animals and their use in breeding programmes. Nat Rev Genet 10, 381–391 (2009). https://doi.org/10.1038/nrg2575
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