Essential Cell Biology 5th edition

Exploring Human Genetics
683
prevalence
of obese and
overweight males (%)
< 20.0
20.0 < 35.0
35.0 < 50.0
50.0 < 65.0
65.0 < 80.0
≥ 80.0
not available
according to the laws of Mendel, their sheer number greatly complicate
the analysis. More importantly, unlike monogenic disorders—which tend
to occur early in life—complex, multigenic diseases often occur much
later. Because of this delay, many of these disorders do not affect an individual’s
likelihood of reproducing. As a result, some of the risk-enhancing
alleles have become quite common in the population, as they are not
eliminated by selection. The resulting disorders can thus affect a large
proportion of the population (Figure 19−37).
Genome-wide Association Studies Can Aid the Search
for Mutations Associated with Disease
Given the complexity of many of the most common human diseases, identifying
the associated genes ECB5 can h17.03-19.37 be a difficult task. One way of uncovering
these genetic risk factors involves analyzing the patterns of inherited
polymorphisms. Investigators typically collect DNA samples from a large
number of people who have the disease and compare them to samples
from a group of people who do not. They look for variants—SNPs, for
example—that are more common among the people who have the disease.
Because DNA sequences that are close together on a chromosome
tend to be inherited together, the presence of such SNPs could indicate
that these variants themselves—or alleles that lie nearby— increase the
risk of the disease (Figure 19−38).
Such genome-wide association studies (GWAS)—which initially focused on
SNPs—have been used to search for genes that predispose individuals to
common diseases, including diabetes, coronary artery disease, rheumatoid
arthritis, and even depression. One such study is described in How
We Know, pp. 684–685. For many of these conditions, environmental as
healthy controls
individual A
B
C
D
E
affected individuals
individual A
B
C
D
E
Figure 19−37 Complex diseases are
widespread geographically and are
common in the human population. This
map shows the global distribution of
overweight and obese males, as determined
by an elevated body mass index (a measure
of an individual’s weight and height).
Conditions such as obesity, which depend
on complex interactions between genetics
and the environment, often occur at
frequencies that can be thousands of times
higher than those of simple, monogenic
disorders. (Adapted from M.A. Jobling
et al., Human Evolutionary Genetics,
2nd ed. New York: Garland Science, 2014.
With permission from Garland Science.)
Figure 19−38 Genes that affect the
risk of developing a common disease
can often be tracked down through
linkage to SNPs. Here, the patterns
of SNPs are compared between two
sets of individuals—a set of healthy
controls and a set affected by a particular
common disease. A segment of a typical
chromosome is shown. For most SNPs
in this segment, it is a random matter
whether an individual has one SNP variant
(red vertical bars) or another (blue vertical
bars); the same randomness is seen both
for the control group and for the affected
individuals. However, in the part of the
chromosome that is shaded in darker
gray, a bias is seen, such that most normal
individuals have the blue SNP variants,
whereas most affected individuals have the
red SNP variants. This finding suggests that
this region contains, or is very close to, a
gene that is involved in the disease. Using
carefully selected controls and thousands of
affected individuals, this approach can help
track down disease-related genes, even
when they confer only a slight increase in
the risk of developing the disease.