Review Article | Published:

Harnessing genomic information for livestock improvement

Abstract

The world demand for animal-based food products is anticipated to increase by 70% by 2050. Meeting this demand in a way that has a minimal impact on the environment will require the implementation of advanced technologies, and methods to improve the genetic quality of livestock are expected to play a large part. Over the past 10 years, genomic selection has been introduced in several major livestock species and has more than doubled genetic progress in some. However, additional improvements are required. Genomic information of increasing complexity (including genomic, epigenomic, transcriptomic and microbiome data), combined with technological advances for its cost-effective collection and use, will make a major contribution.

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Related links

dbSNP: https://www.ncbi.nlm.nih.gov/projects/SNP

International Mouse Phenotype Consortium: http://www.mousephenotype.org

NCBI Genome database: https://www.ncbi.nlm.nih.gov/genome

Online Mendelian Inheritance in Animals: http://www.omia.org/home

Online Mendelian Inheritance in Man: https://www.omim.org

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Acknowledgements

C.C. is Senior Research Associate of the Fonds de la Recherche Scientifique (FRS-FNRS). Research in animal genomics conducted by the authors is funded by the European Research Council (ERC) Advanced DAMONA, H2020 GpE and WALInnov CAUSEL grants to M.G. and the DGARNE Rilouke and ULiège RetroBlue grants to C.C. The authors are grateful to T. Druet for fruitful discussions and comments on the manuscript and to M. Goddard for excellent discussions over the years.

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Nature Reviews Genetics thanks D. Garrick and A. Legarra for their contribution to the peer review of this work.

Author information

All authors researched data for the article, made substantial contributions to discussions of the content and reviewed and/or edited the manuscript before submission. M.G. and B.H. wrote the article.

Competing interests

The authors declare no competing interests.

Correspondence to Michel Georges.

Supplementary information

  1. Supplementary Tables 1 and 2

Glossary

Within-breed selection

A process by which sires and dams that have above average breeding values are selected as parents to produce the next generation of animals.

Genetic gains

Differences in the average breeding values of the population before and after selection. Genetic gain is a function of the amount of genetic variance, the accuracy of selection, the intensity of selection and the generation interval.

Quantitative trait loci

(QTL). Regions in the genome that encompass genetic variants with an effect on a quantitative trait of interest.

Genome-wide association studies

(GWAS). Scan of the entire genome to identify genetic variants for which variation in genotype is associated with variation for one or more phenotypes of interest.

Genomic selection

(GS). An ensemble of methods to estimate the breeding values of individual animals on the basis of genome-wide single-nucleotide polymorphism genotype information.

Single-nucleotide polymorphism arrays

(SNP arrays). Microarrays used to determine the genotype of individuals for hundreds to millions of SNPs at once.

Progeny testing

(PT). An approach by which the breeding value of an animal is estimated from phenotypic measures made on its progeny.

Genetic architecture

The description of the number, location and effects of the genetic variants that affect a phenotype of interest.

Genotype imputation

The in silico prediction of the genotype of an individual for ungenotyped variants on the basis of known genotypes at neighbouring variants and a reference population with genotype information for all variants. Imputation exploits the nonrandom association of alleles at neighbouring variants, referred to as linkage disequilibrium.

Soft sweeps

The process by which the frequency of a favourable old variant rapidly increases in the population by positive selection until eventual fixation. Soft sweeps are not associated with the concomitant fixation of one predominant haplotype, as the variant has been distributed over multiple haplotypes by recombination before selection. Old variants that are substrates for new selection constitute the standing variation in the population.

Epigenome

The combination of chemical modifications of the DNA sequence (such as cytosine methylation) or nucleosomes (such as methylation of Lys 27 of histone H3) that mark functionally distinct segments of the genome (such as active enhancers) and are inherited mitotically and/or meiotically.

ChIP-Seq

A combination of chromatin immunoprecipitation and next-generation sequencing for genome-wide mapping of binding sites occupied by specific DNA-binding proteins or chromatin regions enriched in specific histone modifications.

DNase-Seq

A method based on next-generation sequencing for genome-wide detection of gene-switch components on the basis of their open chromatin conformation and resulting hypersensitivity to digestion by DNase I.

ATAC-Seq

An assay based on next-generation sequencing for genome-wide detection of gene-switch components on the basis of their open chromatin conformation and resulting increased accessibility to transposase Tn5.

Expression quantitative trait loci

(eQTL). Quantitative trait loci that influence the transcript levels of specific genes. Cis-eQTL are due to regulatory variants that control the levels of RNA molecules transcribed from gene copies located on the same DNA molecule as the variant. Trans-eQTL are due to regulatory variants that can also control the levels of RNA molecules transcribed from gene copies located on different DNA molecules to the variant (homologous or other chromosomes).

Pleiotropy

The ability of a genetic variant to affect more than one phenotype.

Hypomorphic

Pertaining to an allele with partial loss of function when compared with the wild-type allele.

Overdominance

The phenotypic superiority (for example, on a quantitative scale) of heterozygotes (‘Aa’) over both homozygous classes (‘AA’ and ‘aa’).

Haplosufficient

Pertaining to genes for which one functional copy is sufficient to ensure normal development and function.

Compound heterozygosity

Pertaining to the inheritance of two distinct mutations in different alleles of the same gene, one from each parent.

Autozygosity mapping

Mapping of a recessive mutation on the basis that all affected individuals will be homozygous for the same (autozygous) haplotype. Typically applied in genetically isolated populations in which the hypothesis of allelic homogeneity is reasonable.

Modifier locus

A locus with variants that may (depending on the genotype of the individual) affect the phenotypic expression conferred by specific variants at another locus. The effects of modifier loci include suppression and epistasis.

Reverse genetic screens

Process aimed at completing the phenotype–genotype map by sorting individuals according to their genotype at a variant with unknown function and searching for shared phenotypes, as opposed to forward genetics, which consists of sorting individuals according to a phenotype and searching for shared variants.

Haplotypes

A combination of alleles at multiple variant positions transmitted by a gamete. The term is often used to describe variants that are located close to each other in the genome.

Linkage disequilibrium

(LD). The nonrandom association of alleles at two or more loci, which is manifest by the over-representation of specific haplotypes and the concomitant under-representation of others.

Selection index

A weighted sum of breeding values for several traits, each weighted by economic or perceived relevance.

Kinship coefficient

A measure of genetic relatedness between two individuals. The kinship coefficient corresponds to the probability that two alleles (one from each individual) drawn at random from the two possible alleles (maternal and paternal) for each individual for a randomly selected locus in the genome are identical by descent. The kinship coefficient between two individuals corresponds to the expected inbreeding coefficient of their putative offspring.

Hard sweeps

The process by which the frequency of a favourable new variant rapidly increases in the population by positive selection until eventual fixation of the variant and the haplotype upon which it occurred.

Balancing selection

A selective force on a locus that leads to a steady state whereby multiple alleles are simultaneously maintained in the population, rather than one allele becoming fixed at the expense of the others.

Non-synonymous

Variants that cause a change in the amino acid sequence of a protein. By contrast, synonymous variants are variants in the open reading frame of a protein-coding gene that do not change the amino acid sequence. Most non-synonymous variants affect the first and second codon positions, while most synonymous variants affect the third codon position.

Intermediate phenotypes

Phenotypes that mediate the link between a causative variant and the end-point disease or agricultural phenotype of interest — includes transcript, protein and metabolite levels.

Gene flow

The passage of alleles between populations as a result of migration or interbreeding.

Polygenic adaptation

The process by which a phenotype caused by many genes evolves in a population under selection, not by massive changes in the frequency of a few variants with major effects on the phenotype (hard and soft sweeps) but by very small changes in the frequency of many variants with minor effects on the phenotype.

Mosaicism

The occurrence of mutations in some but not all cells of an organism that is entirely derived from a single zygote.

Gartner hype cycle

A model first proposed by the Gartner firm to explain the phases of maturation, adoption and social application of new technologies.

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Further reading

Fig. 1: Identification of mutations and genes causing monogenic defects in livestock.
Fig. 2: Selection procedure of elite dairy sires and cows.
Fig. 3: Identifying cows with subclinical mastitis by bulk genotyping of tank milk.