30.5: Complex Traits

Last updated
Save as PDF

Page ID: 41197

\( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \) \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)\(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\) \(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\)\(\newcommand{\AA}{\unicode[.8,0]{x212B}}\)

Linkage analysis has proven to be highly effective in studying the genetic basis of Mendelian (single gene) diseases. In the past three decades, thousands of genes have been identified as contributing to Mendelian diseases. We have identified the genetic basis of disease such as sickle cell anemia, cystic fibrosis, muscular dystrophy, and severe forms of common diseases such as diabetes and hypertension. For these diseases, mutations are severe and obvious; the environment, behavior, and chance have little effect. Figure 30.5 shows this explosion in published associations.

However, most diseases (and many other traits of interest) are not Mendelian. These complex traits arise from the interactions of many genes and possibly the environment and behavior. A canonical complex trait is human height: it is highly heritable, but environmental factors can affect it. Recently, researchers have identified hundreds of variants which are associated with height [2, 25].

Linkage analysis is not a viable approach to find these variants. The first complex trait mapping occured in 1920 by Altenburg and Muller and involved the genetic basis of truncated wing in D. Melanogaster. The polygenicity, or distribution of a complex trait across a large number of genes, provides a fundamental challenge to determining which genes are associated with a phenotype. In complex traits, instead of one gene determining a disease or trait (as in Mendelian inheritance), many genes each exert a small influence. The effect of all of these genes, as well as environmental influences, combine to determine an individual outcome. Furthermore, most common diseases work this way. This is due to the fact that selection agains each individual genotypic difference is very small, because there is no one difference that is causal for the disease. This way, complex traits ”survive” evolution, because they are not targets for selection.

source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Figure 30.6: Different types of genetic variation