Page 43 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

2.3 Mendelian Inheritance in Humans 35

TABLE 2.2 How to Recognize Dominant the carrier who supplied the original CF allele, but we do
and Recessive Traits in Pedigrees not know if it was the male or the female. As with an am-
biguous dominant phenotype in peas, the unknown second
Dominant Traits allele is indicated by a dash (–).
1. Affected children always have at least one affected parent. In Fig. 2.24a, a mating between the unrelated carriers
VI-1 and VI-2 produced a child with cystic fibrosis. How
2. Dominant traits show a vertical pattern of inheritance: The
trait shows up in every generation. likely is such a marriage between unrelated carriers for a re-
cessive genetic condition? The answer depends on the gene in
3. Two affected parents can produce unaffected children, if both
parents are heterozygotes. question and the particular population into which a person is
born. As Table 2.1 shows, the incidence of genetic diseases
Recessive Traits
(and thus the frequency of their carriers) varies markedly
1. Affected individuals can be the children of two unaffected among populations. Such variation reflects the distinct genetic
carriers, particularly as a result of consanguineous matings.
histories of different groups. The area of genetics that analyzes
2. All the children of two affected parents should be affected. differences among groups of individuals is called population
3. Rare recessive traits show a horizontal pattern of inheritance: genetics, a subject we cover in detail in Chapter 21. Notice that
The trait first appears among several members of one in Fig. 2.24a, several unrelated, unaffected people, such as II-1
generation and is not seen in earlier generations. and II-4, married into the family under consideration. Al-
4. Recessive traits may show a vertical pattern of inheritance if though it is highly probable that these individuals are homozy-
the trait is extremely common in the population. gotes for the normal allele of the gene (CF CF ), a small
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chance (whose magnitude depends on the population) exists
not they are related, carrier parents are both heterozygotes. that any one of them could be a carrier of the disease.
Thus among their offspring, the proportion of unaffected to Genetic researchers identified the cystic fibrosis gene
affected children is expected to be 3:1. To look at it another in 1989, soon after the Huntington disease gene was identi-
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way, the chances are that 1 out of 4 children of two heterozy- fied. The normal, dominant CF allele makes a protein
gous carriers will be homozygous cystic fibrosis sufferers. called cystic fibrosis transmembrane conductance regula-
You can gauge your understanding of this inheritance tor (CFTR). CFTR protein forms a channel in the cell
pattern by assigning a genotype to each person in Fig. 2.24 membranes that controls the flow of chloride ions through
and then checking your answers against the caption. Note lung cells. Recessive CF disease alleles either produce no
that for several individuals, such as the generation I indi- CFTR or produce nonfunctional or less functional versions
viduals in part (a) of the figure, it is impossible to assign a of the protein (Fig. 2.25). Because of osmosis, water flows
full genotype. We know that one of these people must be into lung cells without CFTR, while a thick, dehydrated

Figure 2.25 Why the allele for cystic fibrosis is recessive. The CFTR protein regulates the passage of chloride ions (green
spheres) through the cell membrane. People who are homozygous for a cystic fibrosis disease allele (CF CF) have the disease because
recessive disease alleles either specify no CFTR protein as shown, or encode abnormal CFTR proteins that do not function at all or do not
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function as well as the normal protein (not shown). Disease alleles (CF) are recessive because CF CF heterozygotes produce CFTR from the
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normal (CF ) allele, and this amount of CFTR is sufficient for normal lung function.

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CF CF or CF CF + CF CF
Outside of the cell
Outside of the cell
mucus

Lipid bilayer of
cell membrane
Inside of the cell
Inside of the cell CFTR protein

–
Cl ions

Normal Cystic fibrosis