Multiple Alleles, Epistasis, and Pleiotropy

I. Multiple Alleles

Most genes exist in populations in more than two allelic forms.

EX.  ABO blood groups in human population:

Four possible phenotypes for one character:
A,  B, AB, or O type.

A, B, refer to two carbohydrates on the surface of red blood cells.

A:  A substance alone on the surface of RBC.

B:   B substance alone on the surface of RBC.

AB:  A and B substance, both exist on the
         surface of RBC.

O:     Neither A nor B substance exist on the
          surface of RBC.

IA:  code for the production of A substance.

IB:  code for the production of B substance.

i:     giving rise to neither A or B sunstance.

ii:  receive homozygous.
IA  and  IB alleles are codominant, both are
expressed in the AB phenotype, and both are dominant to the i allele.

Six genotypes are possible to control ABO character.
Phenotype group Genotype Antigen Antibodies present 
in blood serum
O ii No a + b
A IA IA        IAi A b
B IB IB        IBi B a
AB IA IB A  B no

Matching compatible blood groups is critical for blood transfusions.

O type can be a universal blood donor.

AB type can receive blood from A type, B type and O
type donor.

Pseudoscience:  Blood type and Character (Don’t believe it)

The personalities of each blood type.  Mr.Masahito and Toshitaka Nomi (November 23, 1997)

Type O Strongly purpose-oriented. Straight desire. Conscious of powerrelationship. Know how to take chances.  Dislike to be subordinate.Expressive.
Type A Considerate about everything. Prefer peaceful human relations.Slow to trust people. Observe social rules and customs.Regard social orderas important Restrain action and expression
Type B Dislike restrictions and one's own way. Non-stereotyped action.Non-stereotyped thinking. Self-conscious and not warped expressions. Makesless distinction of things. Not conscious of circumstances. Don't caresocial rules and customs.
Type AB Rational thinking. Good critic and analyst. To participateand contribute to the society. Good at adjusting human relations. Hopeto be in harmony with the society. Feels distant from the society.

  Epistasis:  When one gene masks or otherwise affects the expression of a different gene. (Do not confuse this with dominance relationships between alleles of the
                     same gene).  A person with genotype hh, there is no H antigen to bind to the A and B antigens, they can have any ABO genotype, even they have
                     blood type O based on phenotype (a blood type).  Fig 5.5

  Pleiotropy  --- One gene, many effects.  Figure 5.6

Multifactorial Traits

I. Characteristics of Multifactorial Traits

A. Continuous:  Characters vary in the population along a continuum.

B. Controlled by many genes (polygenic):  an addictive effect of two or more genes on a single
     phenotypic character.

C. Strongly influenced by environment:  sunshine on skin color, school/family on IQ?

D. Controlled by addictive genes with nodominance.

II. Examples of Multifactorial Traits:

Fingerprint patterns, height, eye color, and skin color...

Fingerprint pattern:  number of dermal ridges

Eye color:  iris colored by the pigment  -- melanin.

Blue eye:  just enough melanin, dark blue or green, brown, or black eyes, make increasingly more melanin in the iris.

Skin color:  melanin production by melanocytes in skin.  We all have about the same number of melanocytes per unit area of skin.  differences in skin color arise from the number and distribution of melanin pieces in the skin cells in the uppermost layers.

III.  Methods Used to Investigate Multifactorial Traits:

        Empiric Risk:  Pridictions of recurrence of certain diseases controlled by multifactorial trait, based on the trait's incidence
                              in a specific population. such as the number of new cases of a particular disorder diagnosed per year in a
                              populatioin of known size.  Table 7.1  cleft lip.

IV. Heritability of Multifactorial Traits

A.  Heritability:  A measure of the degree to which the variance in the distribution of
                         a phenotype is due to genetic causes.

It estimates the percentage of the phenotypic variation for a particular trait that is due to genes in a certain population at a certain time.  Fig. 7.8 and Table 7.2.

Heritability equals 1.0 for a trait that is completely the result of gene action, and 0 if it is entirly caused by an environmental influence.  Height has a heritability of 0.8; body mass is 0.55.
Heritability changes as the environment changes.

Correlation coefficient:  To compare the actural proportion of pairs of people related in a certain manner who share a particular trit, to the expected proportion of pairs that would share it if it were inherited in a Mendelian fashion.  Table 7.3.

Skin Color, a controversial view:

A Biblical View of Inheritance in Human Skin Color.  (for your reference…)
1. Adam and Eve were the first parents of all the races. Adam and Eve contained all the genetic information from which eventually all the races came.

2. From Adam to Noah, all descendants of Adam and Eve were probably all mid-brown color since Adam and Eve were also mid-brown.

3. After the global flood and the tower of Babel incident, descendants of Noah separated into people groups according to their own languages and traveled to different parts of the world.

4. As different "people groups" were exposed to different environments, natural selection occurred resulting in certain genetic traits to be enhanced for adaptability (for example: darker skin pigmentation for environments with more intense sunlight due to the genetic "potential" to increase more melanin).

5. As the "people groups" were isolated and intermarried with each other with a certain group, they eventually lost certain genes that were not needed for adaptability. (That would explain, from this point of view, why African Negroes who move to different northern environments or European Whites who move down to Africa, do not change back to another color because over time they previously lost the genetic potential to do so.)

A Modern Molecular Biology Interpretation of this view:

There are at least three and perhaps four genes involved in skin color and several alleles at each gene producing differing amounts of melanin.

Adam and Eve would not necessarily need to possess the entire range of skin gene possibilities since there is some time for accumulation of mutations between them and Noah's sons. With that said, since Adam and Eve would both possess two copies of each gene, that means a possible total of at least 4 different alleles at each gene and if there are 3 different genes, that means 12 different alleles which could be combined 144 different ways. This would seem more than adequate to accommodate the full range of human skin color.

A case study showing the effect of three skin color genes (each gene with two alleles):  at each locus, one allele adds a measure of color, whereas the other adds none.

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.
Gametes ABC ABc AbC Abc aBC aBc abC abc
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

6: is the darhest color; 0: is the weakest color.

IQ  (Intelligence Quotient):

IQ is controlled by more than one genes, and is considered as quantitative traits.

A study of monozygotic twins (identical twins):

Bouchard and McCue (1981);
Bouchard, Lykken, McGue, Segal, & Tellegen (1990)

Dr. Bouchard at the U of MN has done extensive research on twins reared apart. He has tested about 86 pairs, all tested in adulthood. Most were separated within the first year of life and some did not even know the other existed until Bouchard got them together. 56 MZ twins reared apart.

RESULTS: there is a correlation between IQ scores of twins reared apart.

Concordance:  the percentage of pairs in which both twins express the traits.

IQ Corr

MZ reared together           0.86
MZ reared apart                0.72

Conclusions:  There is an inherited component to IQ. At most it accounts for about 50% of the variability.
                       The rest will be environmental?

Ten years later (August 8, 2000)…  BBC News Online: Sci/Tech

“Genius of Genes” by Pallab Ghosh

US researchers believe they have identified the parts of the human genome  involved in developing a person's intelligence.
The researchers, working for the US National Institutes of Health, analyzed the DNA of 200 of the brightest kids in America and compared them with the genetic material from ordinary children.
The team believes more than one gene is involved - and that these genes can  make a big difference to a person's intelligence. The research was led by Professor Robert Plomin.

"I think we need to recognize that genetic influences are important and that we will find genes for intelligence," he told the BBC. "Each may account for a small piece of the action, but together they give us a significant source of prediction for intelligence."

The next step will be to discover what these genius genes do. One theory is that they help make nerve cells. They help transmit signals, our thoughts if you like, from one part of the brain to another.

              The impact of this study…

V.  Some Multifactorial Traits:

1.  Heart Health

        E4:  An allele of a gene that encodes apolipoprotein E, increases the risk of a heart attack threefold in people who smoke.

        20 to 50 genes regulate blood pressure.

2.  Body weight.

    Leptin and associated proteins

    Environmental influences on obesity