Page 41 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

2.3 Mendelian Inheritance in Humans 33

Figure 2.23 Why the allele for Huntington disease is A Horizontal Pattern of Inheritance
+
dominant. People who are HD HD or HD HD exhibit Huntington Indicates a Rare Recessive Trait
disease because the HD allele produces an abnormal Htt protein
+
that damages nerve cells. Homozygotes for the normal allele (HD Unlike Huntington disease, most confirmed single-gene
+
HD ) produce only normal Htt protein and do not have the disease. diseases in humans are caused by recessive alleles. One
The disease allele (HD) is dominant because even when the normal
+
protein is present—in HD HD heterozygotes—the abnormal protein reason is that, with the exception of late-onset traits, delete-
damages nerve cells. HD HD homozygosity is possible because the rious dominant alleles are unlikely to be transmitted to the
abnormal Htt protein retains some function of the normal protein. next generation. For example, if people affected with Hun-

+
HD HD + HD HD + HD HD tington disease all died by the age of 10, the disease would
Normal Disease disappear from the population. In contrast, individuals can
carry one allele for a recessive disease without ever being
affected by any symptoms.
Figure 2.24 shows three pedigrees for cystic fibrosis,
the most commonly inherited recessive disease among
Caucasian children in the United States. A double dose of
+
HD + Normal Htt protein the recessive CF allele (meaning the absence of a CF
allele) causes a fatal disorder in which the lungs, pancreas,
HD Abnormal Htt protein and other organs become clogged with a thick, viscous
mucus that can interfere with breathing and digestion. One
in every 2000 white Americans is born with cystic fibrosis,
and only 10% of them survive into their 30s.
molecular mechanisms that may result in a disease allele Note two salient features of the cystic fibrosis pedigrees.
that is dominant to the normal allele of a particular gene. First, the family pattern of people showing the trait is often
No effective treatment yet exists for Huntington dis- horizontal: The parents, grandparents, and great-grandparents
ease, and because of its late onset, there was until the 1980s of children born with cystic fibrosis do not themselves
no way for children of a Huntington parent to know before manifest the disease, while several brothers and sisters in a
middle age—usually until well after their own childbearing single generation may. A horizontal pedigree pattern is a
years—whether they carried the Huntington disease allele strong indication that the trait is recessive. The unaffected
(HD). Most people with the disease allele are HD HD parents are heterozygous carriers: They bear a dominant
+
heterozygotes, so their children would have a 50% proba-
bility of inheriting HD and, before they are diagnosed, a
25% probability of passing the defective allele on to one of Figure 2.24 Cystic fibrosis: A recessive condition. In (a),
the two affected individuals (VI-4 and VII-1) are CF CF; that is,
their children. homozygotes for the recessive disease allele. Their unaffected
In the mid-1980s, with new knowledge of the gene, parents must be carriers, so V-1, V-2, VI-1, and VI-2 must all be CF
molecular geneticists developed a DNA test that deter- CF . Individuals II-2, II-3, III-2, III-4, IV-2, and IV-4 are probably also
+
mines whether an individual carries the HD allele. (This carriers. We cannot determine which of the founders (I-1 or I-2) was
+
test will be explained in detail in Chapter 11.) Because of a carrier, so we designate their genotypes as CF –. Because the CF
allele is relatively rare, it is likely that II-1, II-4, III-1, III-3, IV-1, and
the lack of effective treatment for the disease, some young IV-3 are CF CF homozygotes. The genotype of the remaining
+
+
adults whose parents died of Huntington disease prefer not unaffected people (VI-3, VI-5, and VII-2) is uncertain (CF –). (b and
+
to be tested so that they will not learn their own fate prema- c) These two families demonstrate horizontal patterns of inheritance.
turely. However, other at-risk individuals employ the test Without further information, the unaffected children in each
+
for the HD allele to guide their decisions about having chil- pedigree must be regarded as having a CF – genotype.
dren. If someone whose parent had Huntington disease (a) I 1 2
does not have HD, he or she has no chance of developing
the disease or of transmitting it to offspring. If the test II 1 2 3 4
shows the presence of HD, the at-risk person and his or her III
partner might choose to conceive a child using in vitro fer- 1 2 3 4
tilization (IVF) technology (described in Chapter 11) that IV 1 2 3 4
allows for genotyping of early-stage embryos. Using IVF, V (b) I 1 2
only embryos lacking the HD disease allele would be intro- 1 2
duced into the mother’s womb. VI II 1 2 3 4 5 6
The Genetics and Society Box Developing Guidelines 1 2 3 4 5
for Genetic Screening discusses significant social and VII (c) I 1 2
ethical issues raised by information obtained from family 1 2 II
pedigrees and molecular tests. 1 2 3 4 5