Mathematical And Statistical Methods For Genetic Analysis

Geneticists now stand on the threshold of sequencing the genome in its entirety. The unprecedented insights into human disease and evolution offered by mapping and sequencing are transforming medicine and agriculture. This revolution depends vitally on the contributions made by applied mathematicians, statisticians, and computer scientists. Kenneth Lange has written a book to enable graduate students in the mathematical sciences to understand and model the epidemiological and experimental data encountered in genetics research. Mathematical, statistical, and computational principles relevant to this task are developed hand-in-hand with applications to gene mapping, risk prediction, and the testing of epidemiological hypotheses. The book covers many topics previously only accessible in journal articles, such as pedigree analysis algorithms, Markov chain, Monte Carlo methods, reconstruction of evolutionary trees, radiation hybrid mapping, and models of recombination. The whole is backed by numerous exercise sets.

Written to equip students in the mathematical siences to understand and model the epidemiological and experimental data encountered in genetics research. This second edition expands the original edition by over 100 pages and includes new material. Sprinkled throughout the chapters are many new problems.

This book covers the statistical models and methods that are used to understand human genetics, following the historical and recent developments of human genetics. Starting with Mendel’s first experiments to genome-wide association studies, the book describes how genetic information can be incorporated into statistical models to discover disease genes. All commonly used approaches in statistical genetics (e.g. aggregation analysis, segregation, linkage analysis, etc), are used, but the focus of the book is modern approaches to association analysis. Numerous examples illustrate key points throughout the text, both of Mendelian and complex genetic disorders. The intended audience is statisticians, biostatisticians, epidemiologists and quantitatively- oriented geneticists and health scientists wanting to learn about statistical methods for genetic analysis, whether to better analyze genetic data, or to pursue research in methodology. A background in intermediate level statistical methods is required. The authors include few mathematical derivations, and the exercises provide problems for students with a broad range of skill levels. No background in genetics is assumed.

Although the basic statistical theory behind modern genetics is not very difficult, most statistical genetics papers are not easy to read for beginners in the field, and formulae quickly become very tedious to fit a particular area of application. Introduction to Statistical Methods in Modern Genetics distinguishes between the necessary and unnecessary complexity in a presentation designed for graduate-level statistics students. The author keeps derivations simple, but does so without losing the mathematical details. He also provides the required background in modern genetics for those looking forward to entering this arena. Along with some of the statistical tools important in genetics applications, students will learn: How a gene is found How scientists have separated the genetic and environmental aspects of a person's intelligence How genetics are used in agriculture to improve crops and domestic animals What a DNA fingerprint is and why there are controversies about it Although the author assumes students have a foundation in basic statistics, an appendix provides the necessary background beyond the elementary, including multinomial distributions, inference on frequency tables, and discriminant analysis. With clear explanations, a multitude of figures, and exercise sets in each chapter, this text forms an outstanding entrée into the rapidly expanding world of genetic data analysis.

Statistics is strongly tied to applications in different scientific disciplines, and the most challenging statistical problems arise from problems in the sciences. In fact, the most innovative statistical research flows from the needs of applications in diverse settings. This volume is a testimony to the crucial role that statistics plays in scientific disciplines such as genetics and environmental sciences, among others. The articles in this volume range from human and agricultural genetic DNA research to carcinogens and chemical concentrations in the environment and to space debris and atmospheric chemistry. Also included are some articles on statistical methods which are sufficiently general and flexible to be applied to many practical situations. The papers were refereed by a panel of experts and the editors of the volume. The contributions are based on the talks presented at the Workshop on Statistics and the Sciences, held at the Centro Stefano Franscini in Ascona, Switzerland, during the week of May 23 to 28, 1999. The meeting was jointly organized by the Swiss Federal Institutes of Technology in Lausanne and Zurich, with the financial support of the Minerva Research Foundation. As the presentations at the workshop helped the participants recognize the po tential role that statistics can play in the sciences, we hope that this volume will help the reader to focus on the central role of statistics in the specific areas presented here and to extrapolate the results to further applications.

Heterogeneity, or mixtures, are ubiquitous in genetics. Even for data as simple as mono-genic diseases, populations are a mixture of affected and unaffected individuals. Still, most statistical genetic association analyses, designed to map genes for diseases and other genetic traits, ignore this phenomenon. In this book, we document methods that incorporate heterogeneity into the design and analysis of genetic and genomic association data. Among the key qualities of our developed statistics is that they include mixture parameters as part of the statistic, a unique component for tests of association. A critical feature of this work is the inclusion of at least one heterogeneity parameter when performing statistical power and sample size calculations for tests of genetic association. We anticipate that this book will be useful to researchers who want to estimate heterogeneity in their data, develop or apply genetic association statistics where heterogeneity exists, and accurately evaluate statistical power and sample size for genetic association through the application of robust experimental design.

A Statistical Approach to Genetic Epidemiology After studying statistics and mathematics at the University of Munich and obtaining his doctoral degree from the University of Dortmund, Andreas Ziegler received the Johann-Peter-Süssmilch-Medal of the German Association for Medical Informatics, Biometry and Epidemiology for his post-doctoral work on “Model Free Linkage Analysis of Quantitative Traits” in 1999. In 2004, he was one of the recipients of the Fritz-Linder-Forum-Award from the German Association for Surgery.