Genetic Variation: A Laboratory Manual

Genetic Variation: A Laboratory Manual Michael P. Weiner, Stacey B. Gabriel, Claiborne Stephens, eds. 472 pages. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2007. $165.00. ISBN 978–087969780–8. Genetic variation is central to all evolutionary change. Hence, the study of genetic variation spans plant and animal breeding, conservation biology, human genetics, and comparative genomics. Despite its fundamental importance in several areas of genetics, there has been a long period of “struggle to measure genetic variation.”1 It was a struggle because markers used to measure genetic variation, such as morphological and biochemical markers, often were limited and influenced by environmental factors. These limitations also impeded progress toward understanding genetic architecture and its influence on phenotype, including human disorders. Fortunately, advances in molecular biology since the late 1970s, specifically our knowledge of single-nucleotide polymorphisms (SNPs) and, more recently, copy number variations (CNVs), have revolutionized our ability to describe variation at all levels of genetic organization: genes, individuals, populations, species, and genera. Unfortunately, molecular techniques to quantify genetic variation are scattered in molecular biology laboratory manuals or buried in specialized publications and specific laboratory protocols. It is therefore a challenge for geneticists, population biologists, genetic epidemiologists, and especially scientists in developing countries to access these resources and use them in their own work. From this perspective, the book Genetic Variation: A Laboratory Manual by Weiner, Gabriel, and Stephens is poised to fulfill this need. An impressive array of investigators, representing both private and academic institutions active in discovering and evaluating genetic variation in plants, animals, and humans have contributed to this volume, although the work is skewed toward describing human genetic variation. The book consists of 5 sections, which represent a logical progression from project initiation to data analysis for any genetic variation project: study design, laboratory protocols, data analysis, variation studies in model organisms, and insights into human variation. In any genetic study, particularly those involving humans and animals, it is absolutely essential to pay attention to legal, ethical, and privacy aspects before collecting biological samples. Insights on the ecological and evolutionary aspects of the population(s) considered in a given project have a direct bearing on the amount of genetic variation detected and its influence on qualitative and quantitative traits. For instance, a limited number of founders, as in the Ashkenazi Jewish, Finnish, or Icelandic populations, could profoundly affect genetic variation in subsequent generations and may also have important health consequences in humans. Estimation of power and sample sizes for performing linkage and association studies, popular software programs to perform these tests, databases maintained by the National Heart, Lung, and Blood Institute on human genetic variation, and methods for mining the HapMap project are adequately covered in the first section. Actual screenshots from the HapMap Web site are included and are indeed very helpful. Section 2 consists of DNA and RNA isolation protocols. Isolation of DNA from a wide variety of tissues, including cell cultures, saliva, and forensic samples, is presented in great detail. This is indeed a very helpful compilation of laboratory procedures. Nevertheless, although RNA isolation for corn is presented, similar approaches are not presented for humans. Isolation of DNA in species such as conifers, which are known to contain large amounts of secondary compounds, would have been helpful. Similarly, many genetic variation studies involve collection of blood and tissue samples in the field under varied environmental conditions. Protocols and insights on this important aspect would have been helpful to field biologists and anthropologists. The discovery of SNPs and CNVs is providing unprecedented insights on the distribution of genetic variation, particularly in humans. Parts 2 and 3 of this section describe SNP and CNV discovery extremely well, including the diverse platforms used for detecting these variants. The editors have aptly categorized microsatellite variation under CNVs, as microsatellites have many demonstrable similarities with CNVs. In fact, major emphasis is given to SNPs and CNVs in the manual. Section 3 deals with the selection of informative SNPs and visualizing the organization of SNPs in the genome using the Haploview program. Similarly, approaches for the analysis of CNVs are discussed briefly in one chapter. From a biologist’s perspective, Mark Daly has given a comprehensive and easily understandable account of determining statistical significance in whole-genome association studies. Likewise, the chapter on detecting natural selection at the molecular level is excellent. Despite these excellent chapters, the population genetic approaches that are used to quantify the distribution of genetic variation, such as nucleotide diversity and F–statistics, and that are so well presented in standard population genetics text books have received cursory attention. It is a pleasure to read the 8 chapters on model organisms in section 4. Each of these chapters provides an overview of the domestication history of the species, within-species diversity, the species’ importance as a model organism, and previous work and significant achievements using it. The authors of the chapter on rice have provided a very useful discussion of the application of newly discovered molecular markers in breeding programs, called marker-assisted selection. The morphological and molecular aspects of diversification of domesticated cats and dogs, along with the levels of admixture, within a given breed provide fascinating examples of evolution under domestication. These chapters could provide insights toward understanding diversity in other domesticated animals, such as horses, cattle, and sheep. Curiously, although Arabidopsis, maize, and rice have found their place in this book, equally important model organisms, such as tomato, drosophila, Caenorhabditis elegans, and zebrafish, are not mentioned. Section 5 is very short, consisting of only 3 chapters. The first chapter by Stoneking and Keyser deals with quantifying human genetic variation by using the paternally inherited Y chromosome and maternally inherited mtDNA markers. The authors have applied almost all the commonly used population genetic approaches to understand the human diversity and evolution in Micronesia. Indeed these studies point toward the broader perspective of what genetic variation is and how it could be applied to understand all the microevolutionary processes of our own species. Butler’s presentation on forensic DNA testing provides one of the most fascinating and successful applications of genetic variation to humans. He has presented every facet of