The study of human inheritance often tends to focus on relatively simple traits. But as we explored in Chapter 2 and elsewhere, there is a broad avenue of molecular and developmental events that connect the DNA with a phenotype. When the work of Gregor Mendel was "rediscovered" in 1900, various researchers attempted to repeat and confirm his observations using a variety of plants and animals, including humans. Some studies supported the Mendelian genetic models. But many other cases were unsuccessful either because the organisms they chose had unusual genetic characteristics, like honeybee drones that are haploid, or because the traits they looked at did not have the simple phenotypic basis that we see in those studied by Mendel. Some people attribute these latter studies to bad luck in choosing an experimental system. But in fact they were setting the stage to explore a parallel, and very important, dimension of genetic complexity.
This is illustrated historically by the work of people like Francis Galton, a cousin to Charles Darwin, and Karl Pearson, one of the founders of modern statistics. A key trait they studied, human height (Figure 10-1), is now known to be influenced both by a number of genes segregating independently and by many environmental variables. The genotypes were not simple, so the application of Mendelian rules could not be detected. Galton's initial work actually predates the rediscovery of Mendel's papers by several decades, and indeed it was hotly debated whether quantitative traits have the same underlying genetic basis as seen in simpler Mendelian traits like flower color and seed shape. But far from being a dead end, work by pioneers like these led to the establishment of an important field of genetics, biometrical or quantitative genetics, based on the statistical analysis of genetic relationships.
Human height was one of the earliest quantitative characters studied in detail. (a) Height distribution (inches) for 175 students in 1914 attending the Connecticut Agricultural College. (b) Graphical presentation of these student heights showing their close fit to a normal distribution. (a: Reprinted with permission from Albert and Blakeslee: Corn and Man. Journal of Heredity. 1914;5:51. Oxford University Press. b: Reprinted with permission from Brooker RJ: Genetics: Analysis & Principles, 3rd ed. New York: McGrawHill, 2008.)
Significant advances over the last couple of decades have seen the emergence of quantitative genetics as a field with important biomedical perspectives. It is leading to a deeper understanding of the way traits are influenced by quantitative trait loci (QTLs). This appreciation of the multilayered genetic underpinnings of normal phenotypic diversity and a large array of significant medical conditions reflects the continuing maturity of genetics as an explanatory science. In this chapter, we will discuss the basis of phenotype assessments and some of the ways this knowledge can be applied to benefit patients.