KEY POINTS * One effect of recombination is to determine the extent of linkage disequilibrium in population DNA samples. * Direct measurement of the recombination rate is difficult and often

impractical. For this reason, population-genetic methods are often used to infer recombination rates from patterns of variation among DNA sequences. * Population-genetic methods can detect

variation in the recombination rate at the level of single genes. * Although simple parsimony methods allow the number of recombination events to be counted, most recombination events are

missed using this approach. * Sophisticated statistical approaches use population-genetic models to estimate recombination rates. * Several statistical methods that estimate the population

biological processes. * Estimated recombination rates enable the detailed interpretation of linkage disequilibrium and haplotype data. ABSTRACT Obtaining an accurate measure of how

recombination rates vary across the genome has implications for understanding the molecular basis of recombination, its evolutionary significance and the distribution of linkage

disequilibrium in natural populations. Although measuring the recombination rate is experimentally challenging, good estimates can be obtained by applying population-genetic methods to DNA

sequences taken from natural populations. Statistical methods are now providing insights into the nature and scale of variation in the recombination rate, particularly in humans. Such

knowledge will become increasingly important owing to the growing use of population-genetic methods in biomedical research. Access through your institution Buy or subscribe This is a preview

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APPLICATIONS OF ANCESTRAL RECOMBINATION GRAPHS Article 30 September 2024 RANK-INVARIANT ESTIMATION OF INBREEDING COEFFICIENTS Article Open access 25 November 2021 GENETIC LOAD: GENOMIC

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Spencer and three anonymous referees for their helpful comments on earlier drafts of this manuscript. Generous support through research fellowships from the Wellcome Trust (to M.P.H.S) and

the Royal Society (to G.A.T.M.) is gratefully acknowledged. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biological Sciences, Imperial College of Science, Technology and

Medicine, London, SW7 2AY, UK Michael P. H. Stumpf * Department of Statistics, University of Oxford, Oxford, OX1 3TG, UK Gilean A. T. McVean Authors * Michael P. H. Stumpf View author

publications You can also search for this author inPubMed Google Scholar * Gilean A. T. McVean View author publications You can also search for this author inPubMed Google Scholar ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare that they have no competing financial interests. RELATED LINKS RELATED LINKS DATABASES LOCUSLINK _LTA_ _LTB_ FURTHER INFORMATION Michael

Stumpf's laboratory Gilean McVean's laboratory _LTA_ and _LTB_ genotypes SHOX genotypes Data of Gabriel _et al_. PHASE software GLOSSARY * LINKAGE DISEQUILIBRIUM (LD). A measure of

genetic associations between alleles at different loci, which indicates whether allelic or marker associations on the same chromosome are more common than expected. * MARGINAL GENEALOGY The

part of a genealogical graph that corresponds to a single locus or stretch of DNA that is inherited without recombination. * MARKER ASCERTAINMENT The process by which new genetic markers

are obtained — for example, by re-sequencing a subset of chromosomes in a population sample. If those markers are population-specific then inferences that are based on them in other

populations might be biased through so-called ascertainment bias. * HAPLOTYPE The combination of alleles or genetic markers that is found on a single chromosome of a given individual. *

INFINITE SITES MUTATION MODEL A model that assumes that there are an infinite number of nucleotide sites and consequently that each new mutation occurs at a different locus. * FOUR-GAMETE

TEST (FGT). If all four possible gametes are observed for two bi-allelic loci then this test infers that a recombination event must have occurred between them (under an infinite sites

mutation model). * PER-GENERATION RECOMBINATION RATE (_r_). The probability of a recombination event occurring during meiosis. * EFFECTIVE POPULATION SIZE (_N_e). The size of the ideal

constant-size population, in which the effects of random drift would be the same as those seen in the actual population. * POPULATION RECOMBINATION RATE (_ρ_). Population-genetic parameters

are generally proportional to the product of a molecular per-generation rate (for example, the per-generation recombination rate, _r_) and the effective population size (_N_e). The

population recombination rate has therefore often been defined as _ρ_ = 4_N_er. * CENSUS POPULATION SIZE Actual population size (total number of individuals) as compared to the theoretical

effective population size. * ESTIMATOR A statistical method that is used to obtain a numerical estimate for a quantity of interest, such as a model parameter. * SUMMARY STATISTIC A

statistical function that summarizes complex data in terms of simple numbers (examples include the mean and variance). * VARIANCE A statistic that quantifies the dispersion of data about the

mean. * LIKELIHOOD SURFACE The likelihood of a parameter is proportional to the probability of obtaining the observed data under a parametric model given the model parameter. The likelihood

surface is a function/curve that specifies how well the data agrees with the predictions made by a parametric model for different values of the model parameter. * MARKOV CHAIN MONTE CARLO A

computational technique for the efficient numerical calculation of likelihoods. * RECURSION A repeated mathematical operation that is often used to aid numerical analysis. * GENE CONVERSION

The non-reciprocal transfer of genetic information between homologous genes as a consequence of mismatch repair after heteroduplex formation. * PHASING Determining the haplotype phase (the

arrangement of alleles at two loci on homologous chromosomes) from genotype data using statistical methods. * ASSOCIATION STUDIES A set of methods that are used to correlate polymorphisms in

genotype to polymorphisms in phenotype in populations. * MODEL MIS-SPECIFICATION The consequence of using a parametric model in the inference process that is different from the true model

under which the data was generated. * CPG ISLANDS Genome sequences of >200 base pairs that have high G+C content and CpG frequency. * TEMPLATE SWITCHING The process by which RNA templates

are switched between viral genomes during reverse transcription. * BOTTLENECK A temporary marked reduction in population size. * SELECTIVE SWEEP The process by which positive selection for

a mutation eliminates neutral variation at linked sites. * HARDY–WEINBERG EQUILIBRIUM A state in which the frequency of each diploid genotype at a locus equals that expected from the random

union of alleles. * HAPLOTYPE-BASED APPROACH An approach to association studies in which the co-inheritance of phenotypes and haplotypes — as opposed to single markers — is statistically

analysed. * TAGGING APPROACH Identifying sub-sets of markers ('tags') that describe patterns of association or haplotypes among larger marker sets. * MINIMUM-DESCRIPTION LENGTH

APPROACHES A concept from information theory, in which all of the information contained in a system (for example, a sample of DNA sequences) is described in the most compact form possible.

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