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Introduction to quantitative genetics

01 Jan 1981-

TL;DR: The genetic constitution of a population: Hardy-Weinberg equilibrium and changes in gene frequency: migration mutation, changes of variance, and heritability are studied.
Abstract: Part 1 Genetic constitution of a population: Hardy-Weinberg equilibrium. Part 2 Changes in gene frequency: migration mutation. Part 3 Small populations - changes in gene frequency under simplified conditions. Part 4 Small populations - less simplified conditions. Part 5 Small populations - pedigreed populations and close inbreeding. Part 6 Continuous variation. Part 7 Values and means. Part 8 Variance. Part 9 Resemblance between relatives. Part 10 Heritability. Part 11 Selection - the response and its prediction. Part 12 Selection - the results of experiments. Part 13 Selection - information from relatives. Part 14 Inbreeding and crossbreeding - changes of mean value. Part 15 Inbreeding and crossbreeding - changes of variance. Part 16 Inbreeding and crossbreeding - applications. Part 17 Scale. Part 18 Threshold characters. Part 19 Correlated characters. Part 20 Metric characters under natural selection.
Topics: Genetic purging (55%), Inbreeding depression (54%), Population genetics (53%), Inbreeding (52%), Population fragmentation (52%)
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Journal ArticleDOI
Teri A. Manolio1, Francis S. Collins1, Nancy J. Cox2, David Goldstein3  +24 moreInstitutions (21)
08 Oct 2009-Nature
Abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

7,195 citations

Journal ArticleDOI
Simon A. Levin1Institutions (1)
01 Dec 1992-Ecology
Abstract: This book is the second of two volumes in a series on terrestrial and marine comparisons, focusing on the temporal complement of the earlier spatial analysis of patchiness and pattern (Levin et al. 1993). The issue of the relationships among pattern, scale, and patchiness has been framed forcefully in John Steele’s writings of two decades (e.g., Steele 1978). There is no pattern without an observational frame. In the words of Nietzsche, “There are no facts… only interpretations.”

5,508 citations

Journal ArticleDOI
01 Apr 2001-Genetics
TL;DR: It was concluded that selection on genetic values predicted from markers could substantially increase the rate of genetic gain in animals and plants, especially if combined with reproductive techniques to shorten the generation interval.
Abstract: Recent advances in molecular genetic techniques will make dense marker maps available and genotyping many individuals for these markers feasible. Here we attempted to estimate the effects of ∼50,000 marker haplotypes simultaneously from a limited number of phenotypic records. A genome of 1000 cM was simulated with a marker spacing of 1 cM. The markers surrounding every 1-cM region were combined into marker haplotypes. Due to finite population size (Ne = 100), the marker haplotypes were in linkage disequilibrium with the QTL located between the markers. Using least squares, all haplotype effects could not be estimated simultaneously. When only the biggest effects were included, they were overestimated and the accuracy of predicting genetic values of the offspring of the recorded animals was only 0.32. Best linear unbiased prediction of haplotype effects assumed equal variances associated to each 1-cM chromosomal segment, which yielded an accuracy of 0.73, although this assumption was far from true. Bayesian methods that assumed a prior distribution of the variance associated with each chromosome segment increased this accuracy to 0.85, even when the prior was not correct. It was concluded that selection on genetic values predicted from markers could substantially increase the rate of genetic gain in animals and plants, especially if combined with reproductive techniques to shorten the generation interval.

5,158 citations

Journal ArticleDOI
Eric S. Lander1, David Botstein1Institutions (1)
01 Jan 1989-Genetics
Abstract: The advent of complete genetic linkage maps consisting of codominant DNA markers [typically restriction fragment length polymorphisms (RFLPs)] has stimulated interest in the systematic genetic dissection of discrete Mendelian factors underlying quantitative traits in experimental organisms. We describe here a set of analytical methods that modify and extend the classical theory for mapping such quantitative trait loci (QTLs). These include: (i) a method of identifying promising crosses for QTL mapping by exploiting a classical formula of SEWALL WRIGHT; (ii) a method (interval mapping) for exploiting the full power of RFLP linkage maps by adapting the approach of LOD score analysis used in human genetics, to obtain accurate estimates of the genetic location and phenotypic effect of QTLs; and (iii) a method (selective genotyping) that allows a substantial reduction in the number of progeny that need to be scored with the DNA markers. In addition to the exposition of the methods, explicit graphs are provided that allow experimental geneticists to estimate, in any particular case, the number of progeny required to map QTLs underlying a quantitative trait.

4,779 citations

Journal ArticleDOI
Russell Lande1, Stevan J. Arnold1Institutions (1)
01 Nov 1983-Evolution
TL;DR: Measures of directional and stabilizing selection on each of a set of phenotypically correlated characters are derived, retrospective, based on observed changes in the multivariate distribution of characters within a generation, not on the evolutionary response to selection.
Abstract: Natural selection acts on phenotypes, regardless of their genetic basis, and produces immediate phenotypic effects within a generation that can be measured without recourse to principles of heredity or evolution. In contrast, evolutionary response to selection, the genetic change that occurs from one generation to the next, does depend on genetic variation. Animal and plant breeders routinely distinguish phenotypic selection from evolutionary response to selection (Mayo, 1980; Falconer, 1981). Upon making this critical distinction, emphasized by Haldane (1954), precise methods can be formulated for the measurement of phenotypic natural selection. Correlations between characters seriously complicate the measurement of phenotypic selection, because selection on a particular trait produces not only a direct effect on the distribution of that trait in a population, but also produces indirect effects on the distribution of correlated characters. The problem of character correlations has been largely ignored in current methods for measuring natural selection on quantitative traits. Selection has usually been treated as if it acted only on single characters (e.g., Haldane, 1954; Van Valen, 1965a; O'Donald, 1968, 1970; reviewed by Johnson, 1976 Ch. 7). This is obviously a tremendous oversimplification, since natural selection acts on many characters simultaneously and phenotypic correlations between traits are ubiquitous. In an important but neglected paper, Pearson (1903) showed that multivariate statistics could be used to disentangle the direct and indirect effects of selection to determine which traits in a correlated ensemble are the focus of direct selection. Here we extend and generalize Pearson's major results. The purpose of this paper is to derive measures of directional and stabilizing (or disruptive) selection on each of a set of phenotypically correlated characters. The analysis is retrospective, based on observed changes in the multivariate distribution of characters within a generation, not on the evolutionary response to selection. Nevertheless, the measures we propose have a close connection with equations for evolutionary change. Many other commonly used measures of the intensity of selection (such as selective mortality, change in mean fitness, variance in fitness, or estimates of particular forms of fitness functions) have little predictive value in relation to evolutionary change in quantitative traits. To demonstrate the utility of our approach, we analyze selection on four morphological characters in a population of pentatomid bugs during a brief period of high mortality. We also summarize a multivariate selection analysis on nine morphological characters of house sparrows caught in a severe winter storm, using the classic data of Bumpus (1899). Direct observations and measurements of natural selection serve to clarify one of the major factors of evolution. Critiques of the "adaptationist program" (Lewontin, 1978; Gould and Lewontin, 1979) stress that adaptation and selection are often invoked without strong supporting evidence. We suggest quantitative measurements of selection as the best alternative to the fabrication of adaptive scenarios. Our optimism that measurement can replace rhetorical claims for adaptation and selection is founded in the growing success of field workers in their efforts to measure major components of fitness in natural populations (e.g., Thornhill, 1976; Howard, 1979; Downhower and Brown, 1980; Boag and Grant, 1981; Clutton-Brock et

4,737 citations

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