Page 67 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

3.2 Extensions to Mendel for Two-Gene Inheritance 59

Figure 3.13 A biochemical explanation for coat color see in Fig. 3.13 why ee is epistatic to both alleles of gene B:
in Labrador retrievers. Protein E activates an enzyme that In ee dogs, no eumelanin is present, so the dogs are yellow
generates eumelanin from a colorless precursor. When protein E is regardless of whether they are B− or bb.
present, only eumelanin is produced. Protein B deposits eumelanin
densely so that the hair is black. Pigment is deposited less densely
without protein B, producing brown hair (chocolate). In the absence The Bombay phenotype in humans An understanding of
of protein E, no eumelanin is produced and instead, pheomelanin recessive epistasis made it possible to resolve an intriguing
(yellow pigment) is synthesized. Homozygous ee dogs are always puzzle in human genetics. In rare instances, two parents
yellow regardless of the gene B genotype. The reason is that who appear to have blood type O, and thus would be pre-
protein B affects eumelanin only, but these ee animals have no dicted to be genotype ii, produce a child who is either blood
eumelanin. A B
EE, Ee BB, Bb type A (genotype I i) or blood type B (genotype I i). This
phenomenon occurs because an extremely rare trait, called
Colorless Protein E Eumelanin Protein B Eumelanin the Bombay phenotype after its discovery in Bombay,
India, superficially resembles blood type O. As Fig. 3.14a
deposited
precursor densely
shows, the Bombay phenotype actually arises from homo-
bb zygosity for a mutant recessive allele (hh) of a second gene
EE, Ee that masks the effects of any ABO alleles that might be
present.
No Protein B Eumelanin
Colorless Protein E Eumelanin not Here’s how it works at the molecular level (Fig. 3.14a).
precursor deposited In the construction of the red blood cell surface molecules
densely that determine blood type, type A individuals make an
ee BB, Bb, bb enzyme that adds polysaccharide A onto a sugar polymer
known as substance H; type B individuals make an altered
No protein E Protein B No form of the enzyme that adds polysaccharide B onto the sugar
eumelanin
No eumelanin deposited polymer H; and type O individuals make neither A-adding
Colorless
precursor No Protein B nor B-adding enzyme and thus have an exposed substance H
in the membranes of their red blood cells. All people of A, B,
or O phenotype carry at least one dominant wild-type H allele
Pheomelanin Pheomelanin for the second gene and thus produce some substance H. In
No protein E deposited contrast, the rare Bombay-phenotype individuals, with

Figure 3.14 Recessive epistasis in humans causes a rare blood type. (a) Homozygosity for the h Bombay allele is epistatic to
the I gene determining ABO blood types. hh individuals fail to produce substance H, which is needed for the addition of A or B sugars at the
A
B
surface of red blood cells. (b) Because h is epistatic to I, rare individuals may appear to have blood type O despite having an I or I allele.
When the masked I allele is expressed in their Hh progeny, these people may be surprised by their child’s blood type.
(a) Molecular basis of the Bombay phenotype (b) How epistasis causes unexpected inheritance pattern of
ABO blood type
Apparent
Type O Type O
A A
hh I I HH ii
A B
I I H– genotype AB phenotype
P

Substance H A
Hh I i
ii H– genotype O phenotype
A sugar No
substance H
B sugar F 1

Type A
hh genotype Bombay phenotype
(Appears to be O)