Page 40 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

32 Chapter 2 Mendel’s Principles of Heredity

would require that the fewest genetically unrelated people Figure 2.22 Huntington disease: A rare dominant trait.
carry the allele. Only the father in Fig. 2.21 would need to All individuals represented by filled-in symbols are heterozygotes
have a dominant disease-causing allele, but both parents (except I-1, who could instead have been homozygous for the
would need to carry a recessive disease-causing allele (the dominant HD disease allele); all individuals represented by open
symbols are homozygotes for the recessive HD normal allele.
+
father two copies and the mother one). However, even the Among the 14 children of the consanguineous mating, DNA testing
information that the trait is rare does not allow us to draw shows that some are HD HD, some are HD HD , and some are HD
+
+
the firm conclusion that it is inherited in a dominant fash- HD . The diamond designation masks personal details to protect
+
ion. The pedigree in the figure is so limited that we cannot confidentiality.
be sure the two parents are themselves unrelated. As we I
discuss later in more detail, related parents might have both 1 2
received the same rare recessive allele from their common II
ancestor. This example illustrates why human geneticists try 1 2 3 4
to collect family histories that cover several generations. III
We now look at more extensive pedigrees for the dom- 1 2 3 4 5 6 7 8 9
inant trait of Huntington disease and for the recessive con- IV
dition of cystic fibrosis. The patterns by which these traits 1 2 3 4 5 6
appear in the pedigrees provide important clues that can V 14
indicate modes of inheritance and allow geneticists to as- 1 2 3
sign genotypes to family members.

A Vertical Pattern of Inheritance Indicates In tracking a dominant allele through a pedigree, you
a Rare Dominant Trait can view every mating between an affected and an unaf-
fected partner as analogous to a testcross. If some of the
Huntington disease is named for George Huntington, the offspring do not have Huntington disease, you know the
New York physician who first described its course. This parent showing the trait is a heterozygote. As an exercise,
illness usually shows up in middle age and slowly destroys you should check your own genotype assignments against
its victims both mentally and physically. Symptoms in- the answers in the caption to Fig. 2.22.
clude intellectual deterioration, severe depression, and Notice also in the legend to Fig. 2.22 that human
jerky, irregular movements, all caused by the progressive geneticists use different symbols than Mendel’s for alleles
death of nerve cells. If one parent develops the symptoms, of genes. In human genotypes, all alleles are written in
his or her children usually have a 50% probability of suffer- uppercase. If the allele specifies a normally functioning
ing from the disease, provided they live to adulthood. Be- gene product, the allele symbol has a superscript +. Alleles
cause symptoms are not present at birth and manifest that specify no gene product or abnormal gene products
themselves only later in life, Huntington disease is known sometimes have no superscript at all, as in the Fig. 2.22
as a late-onset genetic trait. legend, but in other cases they have a superscript other than
How would you proceed in assigning genotypes to the + that signifies a particular type of abnormal allele. (See
individuals in the Huntington disease pedigree depicted in the Appendix Guidelines for Gene Nomenclature for
Fig. 2.22? First, you would need to find out if the disease- further discussion of genetic notation.)
producing allele is dominant or recessive. Several clues Like Mendel’s pea genes, the gene that causes Hun-
suggest that Huntington disease is transmitted by a domi- tington disease has been identified and studied at the
nant allele of a single gene. Everyone who develops the molecular level. In fact, in 1988 this was the first hu-
disease has at least one parent who shows the trait, and in man disease gene identified molecularly using methods
several generations, approximately half of the offspring are that will be described in Chapter 11. The protein prod-
affected. The pattern of affected individuals is thus vertical: uct of the Huntington disease gene, called Huntingtin or
If you trace back through the ancestors of any affected in- Htt, is needed for the proper physiology of nerve cells,
dividual, you would see at least one affected person in each but the protein’s precise role in these cells is not yet
generation, giving a continuous line of family members understood. The dominant disease allele (HD) specifies
with the disease. When a disease is rare in the population as a defective Htt protein that over time damages nerve
a whole, a vertical pattern is strong evidence that a domi- cells (Fig. 2.23).
nant allele causes the trait; the alternative would require The disease allele is dominant to the normal allele be-
that many unrelated people carry a rare recessive allele. (A cause the presence of the normal Htt protein in heterozy-
recessive trait that is extremely common might also show gotes does not prevent the abnormal protein from damaging
up in every generation; we examine this possibility in Prob- the cells. It is important to note that this explanation for the
lem 40 at the end of this chapter.) Huntington disease allele is only one of many different