Continuous Variation and Rh Blood Factor
Multiple Gene (Polygenic) Inheritance
Gamete ABC
AbC
aBC
abC
ABc
Abc
aBc
abc
s
ABC
6
5
5
4
5
4
4
3
ABc
5
4
4
3
4
3
3
2
AbC
5
4
4
3
4
3
3
2
Abc
4
3
3
2
3
2
2
1
aBC
5
4
4
3
4
3
3
2
aBc
4
3
3
2
3
2
2
1
abC
4
3
3
2
3
2
2
1
abc
3
2
2
1
2
1
1
0
Table 1. Polygenic inheritance in people showing a cross
between two mulatto parents (AaBbCc x AaBbCc). The
offspring contain seven different shades of skin color
based on the number of capital letters in each genotype.
Polygenic Inheritance: Human skin color is a good example of
polygenic (multiple gene) inheritance. Assume that three "dominant"
capital letter genes (A, B and C) control dark pigmentation because
more melanin is produced. The "recessive"alleles of these three genes
(a, b & c) control light pigmentation because lower amounts of
melanin are produced. The words dominant and recessive are placed
in quotation marks because these pairs of alleles are not truly
dominant and recessive as in some of the garden pea traits that
Gregor Mendel studied. A genotype with all "dominant" capital genes
(AABBCC) has the maximum amount of melanin and very dark skin.
A genotype with all "recessive" small case genes (aabbcc) has the
lowest amount of melanin and very light skin. Each "dominant"
capital gene produces one unit of color, so that a wide range of
intermediate skin colors are produced, depending on the number of
"dominant" capital genes in the genotype. For example, a genotype
with three "dominant" capital genes and three small case "recessive"
genes (AaBbCc) has a medium amount of melanin and an
intermediate skin color. This latter genotype would be characteristic
of a mulatto.
In the following cross between two mulatto genotypes (AaBbCc x
AaBbCc), each parent produces eight different types of gametes and
these gametes combine with each other in 64 different ways
resulting in a total of seven skin colors. The skin colors can be
represented by the number of capital letters, ranging from zero (no
capital letters) to six (all capital letters). The approximate shades of
skin color corresponding to each genotype are shown in Table 1.
Note: Skin color may involve at least four pairs of alleles with nine
(or more) shades of skin color.
The cross in Table 1 can also be shown with the bionomial
expansion (a + b)6 where the letter a = number of capital letters and
the letter b = number of small case letters. Each term in the
expression represents the number of offspring with a specific skin
color phenotype based on the number of capital letters in the
genotype. For example, 20 offspring have three capital letters in their
genotype and have a skin color that is intermediate between very
dark with all caps (AABBCC) and very light with no caps (aabbcc).
(a + b)6 = a6 + 6 a5b + 15 a4b2 + 20 a3b3 + 15 a2b4 + 6 ab5 + b6
6 Caps 5 Caps 4 Caps
3 Caps
2 Caps
1 Cap 0 Caps
Multiple gene (polygenic) inheritance explains many plant and
animal traits where there is a wide variation between extreme
phenotypes, with most individuals having intermediate phenotypes.
Some examples of polygenic inheritance are: human skin and eye
color; height, weight and inteligence in people; and kernel color of
wheat. In fact, kernel color in wheat is nicely shown in Table 2.
Table 2 is essential the same as Table 1, except the extremes in
color are dark red and white, rather than black and white. In
polygenic inheritance the "dominant" capital genes are additive,
each capital gene adding one unit of color to the genotype. With
more capital genes, the phenotype (appearance) gets darker. The
garden peas studied by Gregor Mendel involved pairs of alleles
with only three possible genotypes and two phenotypes per trait.
For example, the gene for round pea (R) is dominant over the gene
for wrinkled pea (r) and only three genotypes are possible: RR, Rr
and rr. These three genotypes produce only two phenotypes: Round
(RR and Rr) and wrinkled (rr). There are no intermediate traits
between round and wrinkled. If all human characteristics were
controlled by simple pairs of dominant and recessive alleles like the
one Mendel studied, we would have tall and short people with no
intermediates. Polygenic inheritance is yet another exception to
Mendel's genetic ratios.
Gamete ABC
AbC
aBC
abC
ABc
Abc
aBc
abc
s
ABC
6
5
5
4
5
4
4
3
ABc
5
4
4
3
4
3
3
2
AbC
5
4
4
3
4
3
3
2
Abc
4
3
3
2
3
2
2
1
aBC
5
4
4
3
4
3
3
2
aBc
4
3
3
2
3
2
2
1
abC
4
3
3
2
3
2
2
1
abc
3
2
2
1
2
1
1
0
Table 2. Polygenic inheritance in wheat showing a cross between two
intermediate parents (AaBbCc x AaBbCc). The offspring contain
seven different shades of kernel color based on the number of capital
letters in each genotype.
Rh Factor: Another Example Of Polygenic Inheritance
Rh Factor: Another interesting example of polygenic inheritance is the
Rh factor. Unlike the A-B-O blood types where all the alleles occur on
one pair of loci on chromosome pair #9, the Rh factor involves three
different pairs of alleles located on three different loci on chromosome
pair #1. In the following diagram, 3 pairs of Rh alleles (C & c, D & d, E
& e) occur at 3 different loci on homologous chromosome pair #1.
Possible genotypes will have one C or c, one D or d, and one E or e from
each chromosome. For example: CDE/cde; CdE/cDe; cde/cde; CDe/CdE;
etc.
In order to determine how many different genotypes are possible, you must
first determine how many different gametes are possible for each parent, then
match all the gametes in a genetic checkerboard (See the following Table 3).
Although the three pairs of genes are linked to one homologous pair of
chromosomes, there are a total of eight different possible gametes for each
parent: CDE, CDe, CdE, Cde, cDE, cDe, cdE, and cde. This number of
gametes is based on all the total possible ways these genes can be inherited
on each chromosome of homologous pair #1. [It is not based on the random
assortment of these genes during meiosis in the parents because all three
genes are closely linked together on the same chromosome; therefore, all
three genes tend to appear together in the same two gametes: CDE and cde.]
The possible different genotypes are shown in the following Table 3:
Gametes
CDE
CDe
CDE
CDE/
CDE
CDE/ CDE/ CDE/ CDE/ CDE/ CDE/ CDE/
CDe CdE Cde cDE cDe
cdE
cde
CDe/
CDE
CdE/
CDE
Cde/
CDE
cDE/
CDE
cDe/
CDE
cdE/
CDE
cde/
CDE
CDe/
CDe
CdE/
CDe
Cde/
CDe
cDE/
CDe
cDe/
CDe
cdE/
CDe
cde/
CDe
CDe
CdE
Cde
cDE
cDe
cdE
cde
CdE
CDe/
CdE
CdE/
CdE
Cde/
CdE
cDE/
CdE
cDe/
CdE
cdE/
CdE
cde/
CdE
Cde
CDe/
Cde
CdE/
Cde
Cde/
Cde
cDE/
Cde
cDe/
Cde
cdE/
Cde
cde/
Cde
cDE
cDe
CDe/ CDe/
cDE cDe
CdE/ CdE/
cDE cDe
Cde/ Cde/
cDE cDe
cDE/ cDE/
cDE cDe
cDe/ cDe/
cDE cDe
cdE/ cdE/
cDE cDe
cde/ cde/
cDE cDe
cdE
cde
CDe/ CDe/
cdE
cde
CdE/ CdE/
cdE
cde
Cde/ Cde/
cdE
cde
cDE/ cDE/
cdE
cde
cDe/ cDe/
cdE
cde
cdE/ cdE/
cdE
cde
cde/ cde/
cdE
cde
Table 3. Polygenic inheritance in the Rh blood factor. Every genotypic
combination with DD or Dd is classified as Rh Positive (red). This is
about 85% of the U.S. population because the D gene is more common
than the C and E genes. Every genotypic combination with dd is classified
as Rh Negative (blue). Since the ratio of C and E genes is much less than
D genes, approximately 15% of the U.S. population are Rh negative (dd).
Consolidating the duplicates, a total of 10 genotypes are homozygous
recessive for the d allele (dd); however, nine of these genotypes are
actually positive for the C and E factors: Cde/cde (0.46%), Cde/Cde
(0.0036%), cdE/cde (0.38%), cdE/cdE (0.0025%), Cde/cdE (0.006%),
CdE/cde (0.008%), CdE/Cde (0.0001%), CdE/cdE (0.0001%), and
CdE/CdE (0.00001%). Therefore, only about 0.86% of the U.S. population
are positive for C and E. Expressed as a decimal, this is 0.0086 or 8.6 out
of 1000. This is why Rh incompatibility involving the C and E genes is
rare in the U.S. population.
Antigen
Immune Antibodies (In Blood Plasma)
(RBC
Membrane)
anti-C
anti--D
anti-E
C (RhC)
------
------
------
D (RhD)
------
RhoGAM & Biology
TypingSerum
------
E (RhE)
------
------
------
Table 4. Rh antibodies primarily utilized in immunoglobulin serums.
More than 98% of all cases of hemolytic disease of the newborn
(maternal-fetal blood incompatibility) are caused by the D antigen, also
referred to as RhD and Rh Positive (+). This is why RhoGam and
standard blood typing kits for general biology labs only contain anti-RhD
(anti-D) antibodies. Anti-C and anti-E antibodies against the C and E
antigens can be associated with maternal-fetal blood incompatibility, but
this is uncommon and only occurs in a small percentage of non-RhD
cases. Apparently immune globulins (such as RhoGam) are not available
to prevent these rare cases. According to Dr. Kenneth J. Moise, Jr.,
formerly of the University of North Carolina Medical School at Chapel
Hill, more than 43 other RBC antigens have been implicated in the non
RhD cases. Especially problematic are the Kell (K1), c, Duffy (Fya) and
Kidd (Jka and Jkb) antigens. A recent study from a tertiary referral center
in New York found 550 cases of antibodies associated with hemolytic
disease of the newborn in 37,506 blood samples taken from women of
reproductive age (1.1% incidence). Anti-D occurred in 25% of the
samples, anti-Kell in 28%, anti-c in 7%, anti-Duffy in 7%, anti-Kidd in
2%, anti-E in 18%, anti-C in 6%, anti-MNS in 6%, and anti-Lutheran in
2%.