Quantitative genetics and the first golden age of genetics: Genetics and Analysis of Quantitative Traits by Michael Lynch and Bruce Walsh

Abstract

Sinauer Associates, 1998. $64.95 hbk (980 pages)ISBN 0 87893 481 2Genetics and Analysis of Quantitative Traits could not be more timely. The field of quantitative genetics ushered in the 20th century, paving the way for what will surely go down in scientific history as the golden age of genetics (or the first of many golden ages to come). As the 20th century winds down, quantitative genetics has renewed importance in the genetic dissection of complex trait etiologies. This encyclopedic volume provides comprehensive coverage of the philosophical and theoretical underpinnings of quantitative genetics (including the overlap with evolutionary biology), thorough derivation of methods, and numerous applications to human and nonhuman systems.The rediscovery in 1900 of Mendel’s work on the genetics of dichotomous traits was the true beginning of this golden age of genetics. At that time, Mendel’s principles were in direct contrast to the Biometrical school of thought which was begun by Galton in the late 19th century and assumed that continuously varying characteristics exhibited blending inheritance. In the early 20th century, there were fierce debates between the mendelians and the biometricians as to whether discrete and continuous traits shared the same hereditary and evolutionary properties. This clash was influenced more by personalities than facts, but delayed the eventual fusion of genetic and evolutionary principles.By the 1920s, quantitative genetics – as we know it today – was developed by Fisher and Wright as a synthesis of statistics, mendelian principles, and evolutionary biology. Quantitative genetics continues to be defined as a statistical branch of genetics based on fundamental mendelian principles extended to continuously varying characteristics, which may or may not also exhibit polygenic (multilocus) etiology. Quantitative genetics was almost immediately embraced by plant and animal breeders; extension into human models was developed theoretically but awaited developments in computer science and molecular biology to become feasible. Quantitative genetics also laid the foundation for many advances in theoretical and applied statistics, such as regression and correlation analyses, ANOVA, path analysis, and support/likelihood approaches.Since those early days of quantitative genetics, there has been an explosion of statistical techniques for genetic studies in human and non-human populations. There has been a further explosion of techniques in molecular biology and molecular genetics, exemplified by the Human Genome Project, which shows all signs of finishing years ahead of schedule. Most initial focus was on ‘simple’ single gene mendelian disorders. Now, as the 20th century draws to a close, there is renewed appreciation of the true complexity of virtually every transmitted trait, leading to an urgent need for the methods of quantitative genetics.We now realize a wide variety of etiologic complexities for even ‘simple’ dichotomous traits. Examples include environmental modifications that mediate the effect of a major locus, environmental triggers that act only on susceptible genotypes at a major locus, interaction of few (perhaps 4–6) loci; stochastic effects, differential mutations within a major locus that lead to different phenotypes and/or differential severity, repeat expansion disorders, uniparental disomy, maternal/paternal effects modifying phenotypic expression, etc. Similar complexities operate in continuously varying traits, with added complexities such as multilocus etiologies and latent traits. Undoubtedly, there are additional complexities yet to be discovered.Genetics and Analysis of Quantitative Traits comprehensively reviews current methods of general applicability to traits with a continuously varying phenotype, and also to dichotomous traits with underlying etiologic complexity. The volume is divided into three major sections – foundations of quantitative genetics, quantitative trait loci, and estimation procedures – plus appendices on topics such as path analysis, maximum likelihood estimation and likelihood ratio tests. A second volume is planned to cover topics on evolution and selection of quantitative traits. The book contains numerous fully-worked examples and illustrations of theoretical concepts, as well as over 2000 references with indexes by subject, author and organism. In addition, the authors maintain a World Wide Web site (http://nitro.biosci.arizona.edu/zbook/book.html) featuring up-to-date lists of computer programs and on-line resources, added information on various topics presented in the text, and updates on the progress of the second volume. Genetics and Analysis of Quantitative Traits is a valuable addition to the genetics book shelf, summarizing the current state of quantitative genetics after a century of development, and serving geneticists well as we begin to tackle complex and/or quantitative traits into the new millennium.