Distinguishing recombination and intragenic gene 
conversion by linkage disequilibrium patterns

Wiehe, Thomas; Mountain, Joanna L.; Parham, Peter; Slatkin, Montgomery

doi:10.1017/s0016672399004036

Cited by 25 publications

(18 citation statements)

References 27 publications

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“…When two distinct gene pools meet, a mosaic genome is produced (Chapman and Thompson 2002), containing intact segments from each contributing founder population (Nordborg and Tavare 2002). Genomes that have undergone recent hybridization will have largely intact ancestral haplotypes, while recombination will act to disrupt these haplotypes in subsequent generations (Wiehe et al 2000). If admixture is ancient, reciprocal recombination, genetic drift, and mutation will have eroded the association between markers from parental populations and a greater density of markers will be required to detect significant associations.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Relative Ages of Admixture in the Bovine Hybrid Zones of Africa and the Near East Using X Chromosome Haplotype Mosaicism

et al. 2006

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Historical hybridization events between the two subspecies of cattle, Bos taurus and B. indicus, have occurred in several regions of the world, while other populations have remained nonadmixed. We typed closely linked X chromosome microsatellites in cattle populations with differing histories of admixture from Africa, Europe, the Near East, and India. Haplotype breakdown will occur as admixed populations age, and longer ancestral haplotypes will remain intact in more recently admixed populations compared to older ones. We genotyped male animals from these populations, obtaining unambiguous haplotypes, and measured levels of linkage disequilibrium (LD) and ancestral mosaicism. Extensive LD, likely to be the result of ongoing admixture, was discovered in hybrid cattle populations from the perimeter of the tsetse zone in West Africa. A Bayesian method to assign microsatellite allele ancestry was used to designate the likely origin of each chromosomal segment and assess the relative ages of admixture in the populations. A gradient of the age of admixture in the African continent emerged, where older admixture has produced more fragmented haplotypes in the south, and longer intact haplotypes, indicating more recent hybridization, feature in the northwest.

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Section: Discussionmentioning

confidence: 99%

Assessing the Relative Ages of Admixture in the Bovine Hybrid Zones of Africa and the Near East Using X Chromosome Haplotype Mosaicism

et al. 2006

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Section: Methodsmentioning

confidence: 99%

“…While the rate of decay of LD by crossing over increases as the distance between the markers increases, with gene conversion it is independent of distance for markers that are sufficiently far apart (Wiehe et al 2000). Therefore, the effects of gene conversion are significant only for short-range markers whereas the effects of crossing over dominate for long-range markers (Andolfatto and Nordborg 1998;Wiehe et al 2000).…”

Section: Methodsmentioning

confidence: 99%

Estimating Recombination Rates From Single-Nucleotide Polymorphisms Using Summary Statistics

Padhukasahasram¹,

Wall²,

Marjoram

et al. 2006

Genetics

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We describe a novel method for jointly estimating crossing-over and gene-conversion rates from population genetic data using summary statistics. The performance of our method was tested on simulated data sets and compared with the composite-likelihood method of R. R. Hudson. For several realistic parameter values, the new method performed similarly to the composite-likelihood approach for estimating crossingover rates and better when estimating gene-conversion rates. We used our method to analyze a human data set recently genotyped by Perlegen Sciences. M EIOTIC recombination is a fundamental biological mechanism that leads to the exchange of genetic material between homologous chromosomes. This process is believed to be associated with some important cellular functions such as the formation of synaptonemal complex and proper chromosomal segregation at the time of meiosis. In evolutionary biology, recombination is important because it generates novel allelic combinations and increases the genetic diversity within a population. The knowledge of how recombination levels vary across a genome is crucial for the design of association-mapping studies as well as evolutionary inference studies and is also of interest from the point of view of basic molecular biology. Therefore, characterizing this variation in the human genome has been the focus of several current research efforts (e.g., Crawford et al. 2004;McVean et al. 2004;Fearnhead and Smith 2005;Jeffreys et al. 2005;Myers et al. 2005).In particular, such studies have been extremely useful for detecting recombination hotspots across the genome as well as in identifying sequence features that are associated with them.Recombination rates can be estimated using a variety of techniques, such as sperm typing (e.g., Jeffreys et al. 2001), pedigree studies (e.g., Kong et al. 2002), and population genetic methods. Although sperm typing can provide estimates at the finest possible resolution, it is currently not practical for whole-genome studies. Existing pedigree studies, on the other hand, can offer wholegenome coverage but cannot provide the required resolution (i.e., at the kilobase scale). Therefore, population genetic approaches have proved to be valuable.These are faster and easier to implement than spermtyping techniques and can offer much higher resolution than is possible from current pedigree studies.Population genetic methods use polymorphism data from DNA sequences sampled from a population. They infer the population-scaled recombination rate r (¼ 4Nr) (where N denotes the effective population size and r denotes recombination fraction) on the basis of simplified models of population evolution. r estimation is a wellstudied problem in the field of population genetics and many different estimators are currently available. The simplest methods are based on ad hoc moment estimators. These are quick and easy to compute but are inaccurate since they do not use the available information efficiently (e.g., Hudson 1987;Hey and Wakeley 1997;Wakeley 1997). In con...

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“…For example, if three loci, A/a, B/b and C/c, are on a chromosome in that order and only B/b is within a conversion track, LD between A/a and B/b and between B/b and C/c is affected by conversion but the LD between A/a and C/c is not. Several methods for inferring the relative rates of gene conversion and recombination have been based on this idea [74][75][76][77][78] .…”

Section: Inbreeding Inversions and Gene Conversionmentioning

confidence: 99%

Linkage disequilibrium — understanding the evolutionary past and mapping the medical future

2008

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Linkage disequilibrium -the nonrandom association of alleles at different loci -is a sensitive indicator of the population genetic forces that structure a genome. Because of the explosive growth of methods for assessing genetic variation at a fine scale, evolutionary biologists and human geneticists are increasingly exploiting linkage disequilibrium in order to understand past evolutionary and demographic events, to map genes that are associated with quantitative characters and inherited diseases, and to understand the joint evolution of linked sets of genes. This article introduces linkage disequilibrium, reviews the population genetic processes that affect it and describes some of its uses. At present, linkage disequilibrium is used much more extensively in the study of humans than in non-humans, but that is changing as technological advances make extensive genomic studies feasible in other species.Linkage disequilibrium (LD) is one of those unfortunate terms that does not reveal its meaning. As every instructor of population genetics knows, the term is a barrier not an aid to understanding. LD means simply a nonrandom association of alleles at two or more loci, and detecting LD does not ensure either linkage or a lack of equilibrium. The term was first used in 1960 by Lewontin and Kojima 1 and it persists because LD was initially the concern of population geneticists who were not picky about terminology as long as the mathematical definition was clear. At first, there were few data with which to study LD, and its importance to evolutionary biology and human genetics was unrecognized outside of population genetics. However, interest in LD grew rapidly in the 1980s once the usefulness of LD for gene mapping became evident and large-scale surveys of closely linked loci became feasible. By then, the term was too well established to be replaced.LD is of importance in evolutionary biology and human genetics because so many factors affect it and are affected by it. LD provides information about past events and it constrains the potential response to both natural and artificial selection. LD throughout the genome reflects the population history, the breeding system and the pattern of geographic subdivision, whereas LD in each genomic region reflects the history of natural selection, gene conversion, mutation and other forces that cause gene-frequency evolution. How these factors affect LD between a particular pair of loci or in a genomic region depends on local recombination rates. The population genetics theory of LD is well developed and is being widely used to provide insight into evolutionary history and as the basis for mapping genes in humans and in other species. HHS Public AccessAuthor manuscript Nat Rev Genet. Author manuscript; available in PMC 2016 November 27. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptIn this article, I will review the definitions of LD and the problems with assessing it, then outline the basic population genetics of LD that tells us how natural select...

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Distinguishing recombination and intragenic gene conversion by linkage disequilibrium patterns

Cited by 25 publications

References 27 publications

Assessing the Relative Ages of Admixture in the Bovine Hybrid Zones of Africa and the Near East Using X Chromosome Haplotype Mosaicism

Assessing the Relative Ages of Admixture in the Bovine Hybrid Zones of Africa and the Near East Using X Chromosome Haplotype Mosaicism

Estimating Recombination Rates From Single-Nucleotide Polymorphisms Using Summary Statistics

Linkage disequilibrium — understanding the evolutionary past and mapping the medical future

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