Page 61 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

3.1 Extensions to Mendel for Single-Gene Inheritance 53

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A allele prove fatal to the animal carrying them, whereas seemingly normal newborns remain healthy for five to six
one copy of the allele produces a yellow coat. This means months but then develop blindness, paralysis, mental im-
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that the A allele affects two different traits: It is domi- pairment, and other symptoms of a deteriorating nervous
nant to A in the determination of coat color, but it is re- system; the disease usually proves fatal by the age of six.
cessive to A in the production of lethality. An allele, such Tay-Sachs disease results from the absence of an active ly-
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as A , that negatively affects the survival of a homozy- sosomal enzyme called hexosaminidase A, leading to the
gote is known as a recessive lethal allele. Note that the accumulation of a toxic waste product inside nerve cells.
same two alleles (A and A) can display different domi- The approximate incidence of Tay-Sachs among live births
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nance relationships when looked at from the point of is 1/35,000 worldwide, but it is 1/3000 among Jewish peo-
view of different phenotypes; we return later to this im- ple of Eastern European descent. Reliable tests that detect
portant point. carriers, in combination with genetic counseling and edu-
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Because the A allele is dominant for yellow coat cational programs, have all but eliminated the disease in
color, it is easy to detect carriers of this particular reces- the United States.
sive lethal allele in mice. Such is not the case, however, for Recessive alleles causing prenatal or early childhood
the vast majority of recessive lethal mutations, as these lethality can be passed on to subsequent generations only
usually do not simultaneously show a visible dominant by heterozygous carriers because affected homozygotes
phenotype for some other trait. Lethal mutations can arise die before they can mate. However, for late-onset diseases
in many different genes, and as a result, most animals, in- causing death in adults, homozygous patients can pass on
cluding humans, carry some recessive lethal mutations. the lethal allele before they become debilitated. An exam-
Such mutations usually remain hidden, except in rare cases ple is provided by the degenerative disease Friedreich
of homozygosity, which in people are often caused by con- ataxia: Some homozygotes first display symptoms of ataxia
sanguineous matings (that is, matings between close rela- (loss of muscle coordination) at age 30–35 and die about
tives). If a mutation produces an allele that prevents five years later from heart failure.
production of a crucial molecule, homozygous individuals Dominant alleles causing late-onset lethality can also
will not make any of the vital molecule and will not sur- be transmitted to subsequent generations; Figure 2.22 illus-
vive. Heterozygotes, by contrast, with only one copy of the trates this fact for the inheritance of Huntington disease. By
deleterious mutation and one wild-type allele, can produce contrast, if the lethality caused by a dominant allele occurs
50% of the wild-type amount of the normal molecule; this instead during fetal development or early childhood, the
is usually sufficient to sustain normal cellular processes allele will not be passed on, so all dominant early lethal
such that life goes on. mutant alleles must be new mutations.
Table 3.1 summarizes Mendel’s basic assumptions
about dominance, the number and viability of one gene’s
Delayed lethality alleles, and the effects of each gene on phenotype, and
In the preceding discussion, we have described recessive then compares these assumptions with the extensions con-
alleles that result in the death of homozygotes prenatally; tributed by his twentieth-century successors. Through
that is, in utero. With some mutations, however, homozy- carefully controlled monohybrid crosses, these later ge-
gotes may survive beyond birth and die later from the del- neticists analyzed the transmission patterns of the alleles
eterious consequences of the genetic defect. An example of single genes, challenging and then confirming the law
is seen in human infants with Tay-Sachs disease. The of segregation.

TABLE 3.1 For Traits Determined by One Gene: Alterations of the 3:1 Monohybrid Ratio

Extension’s Effect on
Extension’s Effect on Ratios Resulting from
What Mendel Described Extension Heterozygous Phenotype an F 1 × F 1 Cross

Complete dominance Incomplete dominance Unlike either homozygote Phenotypes coincide with
Codominance genotypes in a ratio of 1:2:1
Two alleles Multiple alleles Multiplicity of phenotypes A series of 3:1 or 1:2:1 ratios
All alleles are equally viable Recessive lethal alleles Heterozygotes survive but may 2:1 instead of 3:1
have visible phenotypes
One gene determines one Pleiotropy: One gene Several traits affected in Different ratios, depending
trait influences several traits different ways, depending on dominance relations for
on dominance relations each affected trait