CHAPTER 18 INTRODUCTION

CORE CONCEPTS

18.1 Complex traits are those influenced both by the action of many genes and by environmental factors.

18.2 Genetic effects on complex traits are reflected in resemblance between relatives.

18.3 Twin studies help separate the effects of genotype and environment on variation in a trait.

18.4 Many common diseases and birth defects are affected by multiple genetic and environmental risk factors.

Biologists initially had a hard time accepting the principles of Mendelian inheritance because they seem so at odds with everyday observations. Common and easily observed traits like height, weight, hair color, and skin color give no evidence of segregation in pedigrees, and simple phenotypic ratios like 3:1 or 9:3:3:1 are not observed for them. The lack of these characteristic ratios raised serious doubt whether Mendel’s principles are valid for common traits—some biologists concluded that they apply only to seemingly trivial traits like round and wrinkled seeds in peas.

At about the time that Mendel was studying inheritance in garden peas, the biologist Francis Galton, a friend and cousin of Charles Darwin, was studying common traits including human height. From studies of height and other common traits in parents and their offspring, Galton discovered general principles in the inheritance of such traits. For example, parents who are tall tend to have offspring who are taller than average but not as tall as themselves. Galton’s principles for the inheritance of common traits did not invoke genes, segregation, independent assortment, or other features of Mendelian inheritance, but they did describe the observations. Not only were genes—what Mendel called “hereditary factors”—thought to be unnecessary in Galton’s theory of inheritance, but also many biologists thought that Galton’s theories and Mendel’s were incompatible.

This, it turned out, was not the case. The traits that Mendel studied are now called single-gene traits because each one is determined by variation at a single gene and the traits are for the most part not influenced by the environment. By focusing on single-gene traits, Mendel was able to infer underlying mechanisms of inheritance based on physical factors we now call genes. By contrast, complex traits, such as human height, are influenced by multiple genes as well as by the environment. As a result, their inheritance patterns are more difficult to follow and simple phenotypic ratios are not observed.

In many ways, complex traits are more important than single-gene Mendelian traits. One reason is their prevalence—complex traits are found everywhere and include most of the traits we can see around us. By contrast, there are relatively few examples of single-gene traits. Complex traits are also important in human health and disease. In the most common disorders—among them heart disease, diabetes, and cancer—single-gene Mendelian inheritance is seldom found. It is therefore important to understand the inheritance of complex traits and common disorders, which are the subjects of this chapter. We begin by describing some of the features of complex traits, and then show how these principles are not only compatible with, but in fact predicted by, Mendelian inheritance. Finally, we describe how modern molecular genetics and genomics have allowed the identification of genes affecting complex traits.