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Domestic-animal genomics: deciphering the genetics of complex traits

Key Points

  • Domestic animals provide unique opportunities for unravelling the genetic basis of phenotypic variation, in particular with regards to complex traits. This is partly because of the extensive diversity among breeds, despite their short evolutionary history, and the possibility of using segregation analysis to map loci that explain phenotypic differences.

  • The progress in domestic-animal genomics has been hampered by a lack of genomic resources, but this will be remediated by the generation of high-quality draft genome sequences for several domestic animals in the near future. The status of ongoing genome projects in domestic animals is reviewed.

  • Genetic analyses of complex traits are challenging because of the small effect of each locus and the environmental noise that affects the phenotype. Epistatic interaction between loci and epigenetic inheritance might further complicate the analysis.

  • The combined use of linkage and linkage-disequilibrium analysis using extended multi-generation families of domestic animals is a promising approach to improve markedly the poor resolution when mapping genes that underlie complex traits. This approach has already led to the identification of the causative mutations for some important quantitative trait loci in domestic animals.

  • A selective sweep occurs when a favourable allele becomes fixed in the population, and it affects the degree of genetic polymorphism at closely linked loci owing to hitch-hiking. The selective sweeps that have occurred during domestication and selective breeding leave footprints in the genome that can be exploited for the identification of haplotypes containing functionally important mutations.

Abstract

One of the 'grand challenges' in modern biology is to understand the genetic basis of phenotypic diversity within and among species. Thousands of years of selective breeding of domestic animals has created a diversity of phenotypes among breeds that is only matched by that observed among species in nature. Domestic animals therefore constitute a unique resource for understanding the genetic basis of phenotypic variation. When the genome sequences of domestic animals become available the identification of the mutations that underlie the transformation from a wild to a domestic species will be a realistic and important target.

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Figure 1: Identical-by-descent mapping.
Figure 2: Loss of heterozygosity owing to a selective sweep of a favourable mutation.
Figure 3: Approaches to mapping and positional cloning of QTLs in domestic animals.

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Acknowledgements

We thank K. Lindblad-Toh and two anonymous reviewers for their useful comments, and M. Fredholm, B. Liu, W. Warren and G. Weinstock for their updates on the status of genome sequencing projects.

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Correspondence to Leif Andersson.

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DATABASES

Entrez

DGAT

LocusLink

Agouti

GHR

IGF2

KITLG

myostatin

PRKAG3

RYR1

FURTHER INFORMATION

Leif Andersson's laboratory

ArkDB

A BAC fingerprint map of the bovine genome

BBSRC ChickEST Database

Beijing Genomics Institute

Bovine genome project

Broad Institute dog genome project

Cat genome project

Chicken genome project

ChickNET

CSIRO cattle genomics

Dog genome project

DogMap

GenBank's trace archive

Horse genome project

Mapping the caprine genome

NHGRI genome sequencing proposals

USDA MARC gene mapping information

UK sheep genome mapping project

US pig gene mapping coordination program

US poultry genome project

The Institute for Genomic Research

Glossary

COMPOSITE INTERVAL MAPPING AND MULTIPLE QTL MAPPING

Methods that increase quantitative trait locus (QTL) mapping resolution in a chromosome interval of interest, by accounting for genetic background noise due to segregation at other QTLs by means of the inclusion of multiple markers as cofactors in the statistical model.

EPISTASIS

The phenotypic expression of genotypes at one locus depends on the genotype at another locus or other loci.

EFFECTIVE POPULATION SIZE

The number of individuals in a theoretically ideal population that are subject to the same amount of genetic drift as the actual population

HETEROZYGOSITY

The frequency of heterozygotes at a locus.

LINKAGE DISEQUILIBRIUM

The non-random association of alleles at different loci.

MALIGNANT HYPERTHERMIA AND HALOTHANE SENSITIVITY

A disorder in which uncontrolled muscle contractions can cause lethal overheating. In pigs, this pathological condition might be induced by stress or exposure to halothane anesthesia. Susceptibility to malignant hyperthermia in pigs and in some human families is caused by mutations in the RYR1 gene, which encodes ryanodine receptor 1.

MÜLLERIAN DUCTS

The structures from which the vagina, cervix, uterus and oviducts derive in the female embryo.

EPIGENETIC INHERITANCE

Inheritance of a molecular modification of DNA (methylation or chromatin structure) that affects gene expression.

ADVANCED INTERCROSS LINES

The subsequent generations (F3, F4 and so on) of an intercross, which are maintained to allow the high-resolution mapping of quantitative trait loci.

HAPLOTYPE

A combination of alleles at different loci that is transmitted together from one generation to the next.

WHOLE-GENOME SHOT-GUN

The random generation of short DNA-sequence reads from the whole genome.

FINGERPRINT MAP

A map of a clone or a genome that is based on the pattern of fragments that are generated by restriction enzyme digestions.

INTERCROSSES

Crosses between different populations.

METHYLATION STATUS

The degree of methylation of the cytosine base in DNA.

SKIM SEQUENCING

The partial random sequencing of a large-insert clone.

ADMIXTURE

The mixing of two genetically differentiated populations.

INTROGRESSION

The transfer of genetic material from one population to another by repeated backcrossing.

GENETICAL GENOMICS

Segregation analysis of gene expression data using genetic markers to trace the inheritance of individual chromosome segments.

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Andersson, L., Georges, M. Domestic-animal genomics: deciphering the genetics of complex traits. Nat Rev Genet 5, 202–212 (2004). https://doi.org/10.1038/nrg1294

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