Review
Admixture as the basis for genetic mapping

https://doi.org/10.1016/j.tree.2008.07.008Get rights and content

Genetic mapping in natural populations is increasing rapidly in feasibility and accessibility. As with many areas in genetics, advances in molecular techniques and statistics are drastically altering how we can investigate inheritance in wild organisms. For ecology and evolution, this is particularly significant and promising, because many of the organisms of interest are not amenable to conventional genetic approaches. Admixture mapping falls within a family of statistical approaches that use natural recombination and linkage disequilibrium between genetic markers and phenotypes as the basis for mapping. Our aim in this review is to provide a snapshot of previous and ongoing research, existing methods and challenges, the nature of questions that can be investigated and prospects for the future of admixture mapping.

Section snippets

Genetics in species colliders

A greater understanding of the genetic basis of adaptations, and of reproductive isolation between species, is a long-standing goal for biologists, in part because the genetics can inform us about the history and processes of adaptation and speciation 1, 2. A variety of methods are utilized for associating phenotypes with particular genotypes, including traditional approaches to genetic mapping, which involve statistical analyses of experimental crosses or populations with known pedigrees.

Applications in ecology and evolution

Although the potential of admixture mapping in evolutionary biology has been recognized for 15–20 years 25, 26, the first successful applications were focused on human traits of medical interest. Examples include recent studies of hypertension, susceptibility to multiple sclerosis, prostate cancer risk and white blood cell count 27, 28, 29, 30, 31. However, multiple studies have identified genetic variants associated with lighter and darker skin pigmentation in humans 32, 33, 34, a trait that

Statistical methods and data acquisition

Progress in admixture mapping is being driven by its application to a growing number of biological systems, outlined above, as well as by the rapid development of new statistical approaches and modeling and of molecular markers with increasing coverage of the genome. Below we provide a brief overview of advances in statistics and markers.

Individuals are expected to have genotypes at focal loci that are consistent with the ancestry of the remainder of their genome. Individual loci that depart

Prospects

The list of organisms studied by admixture mapping is growing. The ongoing studies outlined in this paper are promising and will be good tests of the value of admixture mapping in diverse taxa. In addition to the methodological challenges discussed in the preceding section, the prospects for admixture mapping also depend on the genomic architecture of traits of interest. For example, the genomic architecture of reproductive isolation might be complex in a highly diverged species pair with many

Acknowledgements

C.A.B. first encountered the analogy between species and particle colliders in a presentation by Michael Wade. We thank Jenny Boughman, Bret Payseur, Katie Peichel, Qiurong Wang, four anonymous referees and the editor for their valuable suggestions for improvement to the manuscript. C.A.B.’s research on admixture mapping is supported by a grant from the U.S. NSF (0701757) and an NIH INBRE grant to the University of Wyoming. C.L.’s work on within-species variation for genomic isolation in

Glossary

Admixture
the mixing of genomes of divergent parental taxa; meant as a more general term than ‘hybridization,’ so as to include taxa that we would not typically refer to as hybridizing (i.e. mating between human populations and between subspecific populations). The mixing of parental genomes can occur at the level of individuals (individual admixture; the focus in this paper) and at the level of populations through mixing of individuals from different source populations (population admixture;

References (84)

  • C.L. Pfaff

    Population structure in admixed populations: effect of admixture dynamics on the pattern of linkage disequilibrium

    Am. J. Hum. Genet.

    (2001)
  • C.J. Hoggart

    Design and analysis of admixture mapping studies

    Am. J. Hum. Genet.

    (2004)
  • C.D. Jiggins et al.

    Bimodal hybrid zones and speciation

    Trends Ecol. Evol.

    (2000)
  • J.A. Coyne et al.

    Speciation

    (2004)
  • H.A. Orr

    The genetic theory of adaptation: a brief history

    Nat. Rev. Genet.

    (2005)
  • L.H. Rieseberg

    Hybrid zones and the genetic architecture of a barrier to gene flow between two sunflower species

    Genetics

    (1999)
  • C. Lexer

    Admixture in European Populus hybrid zones makes feasible the mapping of loci that contribute to reproductive isolation and trait differences

    Heredity

    (2007)
  • S.M. Rogers

    Combining the analyses of introgressive hybridisation and linkage mapping to investigate the genetic architecture of population divergence in the lake whitefish (Coregonus clupeaformis, Mitchill)

    Genetica

    (2001)
  • A. Darvasi et al.

    The beauty of admixture

    Nat. Genet.

    (2005)
  • M.W. Smith et al.

    Mapping by admixture linkage disequilibrium: advances, limitations and guidelines

    Nat. Rev. Genet.

    (2005)
  • L.H. Rieseberg et al.

    Genetic mapping in hybrid zones

    Am. Nat.

    (2002)
  • D.T. Redden

    Regional admixture mapping and structured association testing: conceptual unification and an extensible general linear model

    PLoS Genet.

    (2006)
  • E. Setakis

    Logistic regression protects against population structure in genetic association studies

    Genome Res.

    (2006)
  • K. Zhao

    An Arabidopsis example of association mapping in structured samples

    PLoS Genet.

    (2007)
  • J. Yu

    A unified mixed-model method for association mapping that accounts for multiple levels of relatedness

    Nat. Genet.

    (2006)
  • N.A. Rosenberg et al.

    A general population-genetic model for the production by population structure of spurious genotype-phenotype associations in discrete, admixed or spatially distributed populations

    Genetics

    (2006)
  • G. Luikart

    The power and promise of population genomics: from genotyping to genome typing

    Nat. Rev. Genet.

    (2003)
  • J.F. Storz

    Using genome scans of DNA polymorphism to infer adaptive population divergence

    Mol. Ecol.

    (2005)
  • J.R. Stinchcombe et al.

    Combining population genomics and quantitative genetics: finding the genes underlying ecologically important traits

    Heredity

    (2008)
  • D. Falush

    Traces of human migrations in Helicobacter pylori populations

    Science

    (2003)
  • G. Liti

    Sequence diversity, reproductive isolation and species concepts in Saccharomyces

    Genetics

    (2006)
  • R. Chakraborty et al.

    Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci

    Proc. Natl. Acad. Sci. U. S. A.

    (1988)
  • D. Briscoe

    Linkage disequilibrium in admixed populations: applications in gene mapping

    J. Hered.

    (1994)
  • D. Reich

    A whole-genome admixture scan finds a candidate locus for multiple sclerosis susceptibility

    Nat. Genet.

    (2005)
  • X. Zhu

    Admixture mapping for hypertension loci with genome-scan markers

    Nat. Genet.

    (2005)
  • M.L. Freedman

    Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men

    Proc. Natl. Acad. Sci. U. S. A.

    (2006)
  • R.C. Deo

    A high-density admixture scan in 1,670 African Americans with hypertension

    PLoS Genet.

    (2007)
  • R.L. Lamason

    SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans

    Science

    (2005)
  • H.L. Norton

    Genetic evidence for the convergent evolution of light skin in Europeans and East Asians

    Mol. Biol. Evol.

    (2007)
  • R.G. Harrison

    Hybrid zones: windows on evolutionary process

    Oxf. Surv. Evol. Biol.

    (1990)
  • N.H. Barton et al.

    Genetic analysis of hybrid zones

  • B.A. Payseur

    Differential patterns of introgression across the X chromosome in a hybrid zone between two species of house mice

    Evolution

    (2004)

    • Cited by (0)

    View full text
    Copyright © 2008 Elsevier Ltd. All rights reserved.