Page 75 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

3.2 Extensions to Mendel for Two-Gene Inheritance 67

each homozygous for recessive, nonfunctional alleles of or separate genes is a naturally occurring version of an
different genes, were both white. experimental genetic tool called the complementation
test. Simply put, when what appears to be an identical
recessive phenotype arises in two separate breeding
Evidence for locus heterogeneity lines, geneticists want to know whether mutations in the
in human pedigrees same gene are responsible for the phenotype in both
Careful examination of many family pedigrees can reveal lines. They answer this question by setting up a mating
whether locus heterogeneity—a property of a trait where between affected individuals from the two lines. If
mutations in any one of two or more genes results in the offspring receiving the two mutations—one from each
same mutant phenotype—explains the inheritance pat- parent—express the wild-type phenotype, complementation
tern of a trait. In the case of deafness, for example, has occurred. The observation of complementation
whether a particular nonhearing man and a particular means that the original mutations affected two different
nonhearing woman carry mutations in the same gene or genes, and for both genes, the normal allele from one
different ones can be determined if they have children parent can provide what the mutant allele of the same
together. If they have only children who can hear, the gene from the other parent cannot. Note that a finding of
parents most likely carry mutations at two different complementation implies that the trait in question must
genes, and the children carry one normal, wild-type al- be heterogeneous.
lele for both of those genes (Fig. 3.23a). By contrast, if You previously saw an example of complementation in
all of their children are deaf, it is likely that both parents Fig. 3.15b. There, the white parental plants were homozy-
are homozygous for a mutation in the same gene, and all gous for nonfunctional alleles of different genes required
of their children are also homozygous for this same mu- for purple pigment synthesis. The F 1 were purple because
tation (Fig. 3.23b). the gamete of each parent provided the wild-type allele that
the other lacked. The pedigree for deafness in Fig. 3.23a, in
which all the children of two deaf parents had normal hear-
Complementation and complementation tests ing, provides another example of this same phenomenon.
The method outlined in Fig. 3.23 for discovering whether By contrast, if all the offspring of affected parents express
a particular phenotype arises from mutations in the same the mutant phenotype, no complementation has occurred.
Each offspring received two recessive mutant alleles—one
from each parent—of the same gene (Fig. 3.23b). A lack of
complementation does not exclude the possibility that a
Figure 3.23 Locus heterogeneity in humans: Mutations trait could be heterogeneous, but instead it simply indicates
in many genes can cause deafness. (a) Two deaf parents can
have hearing offspring if the mother and father are homozygous for that the parents involved in the particular cross had mutant
recessive mutations in different genes. (b) Two deaf parents with alleles of the same gene.
mutations in the same gene may produce all deaf children. You can quiz your understanding of the related con-
(a) Mutations in two di erent genes cepts of locus heterogeneity and complementation by con-
I sidering a form of albinism known as ocular-cutaneous
1 2 albinism (OCA). People with this inherited condition have
P AA bb aa BB
little or no pigment in their skin, hair, and eyes (Fig. 3.24a).
II
1 2 3 4 5 The horizontal inheritance pattern seen in Fig. 3.24b sug-
Complementation gests that OCA is determined by the recessive allele of one
gene, with albino family members being homozygotes for
F 1 Aa Bb that allele. But a 1952 paper on albinism reported a family
Genetic mechanism of in which two albino parents produced three normally pig-
complementation
(b) Mutations in the same gene mented children (Fig. 3.24c). How would you explain this
phenomenon?
I The answer is that albinism is another example of
1 2
locus heterogeneity: Mutant alleles at any one of several
P AA bb AA bb
II different genes can cause the condition. The reported
1 2 3 4 mating was, in effect, an inadvertent complementation
Noncomplementation
test. The complementation observed showed that one
albino parent was homozygous for an OCA-causing muta-
tion in gene A, while the other albino parent was
F 1 AA bb
Genetic mechanism of homozygous for an OCA-causing mutation in a different
noncomplementation gene, B.