The term pleiotropy (Greek: pleion = more) is used to describe a gene that affects more than one characteristic of the individual. A gene with multiple phenotype effects is called pleiotropic.

The genetic disorder sickle cell anemia is a classic example how the alleles at a single locus can have pleiotropic effect. There is a wide range of symptoms characteristic of an individual who is homozygous, recessive for the disorder sickle cell. (Symptoms: Blood flow to the body parts is reduced resulting in periodic fever, sever pain, damage to various organs including heart, brain, kidneys, causing anemia, paralysis, pneumonia, rheumatism, kidney failure and spleen damage.) 

What is Epistasis?

When gene present on one gene locus suppresses expression of gene present on the same or other chromosome, it is called epistasis.

Types of epistasis
The epistatic gene may be dominant or recessive.

Dominant epistasis
The epistatic gene is dominant over its own allele.
It can exert epistatic effect in homozygous as well as in heterozygous condition.

Recessive epistasis
The recessive epistatic gene can have its epistatic influence only in homozygous condition.

Duplicate Recessive Epistasis
Complementary genes, are two pairs of genes present on separate gene loci that interact jointly to produce only one phenotypic character, neither of them if present alone expresses itself. It means these genes are complementary to each other.

Example 1
In sweet peas, it would appear that there are two genes affecting pigmentation and that being homozygous recessive in either gene results in a lack of color. If the two varieties of white plants are crossed, the have purple flowers but among the F2, 9/16 have purple flowers. Since the ratio is in sixteenths, the F, plants must have been di-hybrid as shown in figure.

The 9:7 ratio instead of a 9:3:3:1 ratio can be explained assuming that both a dominant A allele and a dominant B allele are required for pigmentation to result. Although the exact details of pigmentation synthesis are known, the metabolic pathway is hypothesized.

If the A allele codes for the first enzyme and the B allele codes for the second enzyme. Then being homozygous recessive for either gene would result in white instead of purple flowers. A similar situation occurs in mammalian animals. If individuals inherit any one of several defects in the metabolic pathway for the synthesis of melanin, the individual is an albino.

Example 2: Bombay Phenotype
The expression of ABO blood type antigens by lA or lB gene depends upon the presence of another gene H. ABO locus is on chromosome 9, while H locus is on chromosome 19. H gene changes a precursor substance into substance H. It produces an enzyme that inserts a sugar onto a precursor glycoprotein on the surface of RBC. Only then antigen A or antigen B specified by IA or IB gene could attach to this sugar of substance H. The recessive allele h cannot insert sugar molecule to glycoprotein. Therefore, hh individuals lack the site of attachment for antigen A or antigen B. A and B antigens cannot adhere to their RBC and fall away. Their RBC lack A and B antigens although they do not lack IA and IB genes. They are phenotypically like O, but are not genotypically O. their phenotype is called Bombay Phenotype.

Problem: How type A and AB parents could produce a child of blood type O.
Solution: Either parents have Bombay Phenotype or A is heterozygous IA i and the other parent is of Bombay phenotype. 

Blood Group – The ABO System

A well-known example of multiple allele is the ABO blood grouping system in human. It was discovered by Karl Landsteiner in 1901. An antigen is usually a foreign substance that enters the body. Antibody is a protein that has been formed in response to antigen. The red blood cells have antigen. The plasma has antibodies. Two antigens A and B and corresponding antibodies have been distinguished. Sometimes clumping occurs when red blood cells of one person are mixed with the blood plasma of another person. On the basis of the reactions mankind are divided into four groups, A, B, AB, O. Some people were found to have ‘A’ antigen some had B and some had both A and B and some had neither A nor B antigen. Those with A type blood did not carry the corresponding anti A antibody, but they did carry anti-B in their plasma. B type people carry anti A but not B. Persons with AB type blood have both A and B antigens associated with the red blood cells, but no Anti A or Anti B antibodies in their plasma. O type individuals have no A and B antigens but carry both anti A and Anti B antibodies in the plasma.

Multiple Alleles for the ABO blood group 
When two different blood groups are mixed, antigen of one reacts with the antibodies (agglutinin which acts as an antibody) of the other, then the RBC clump with one another. The clumping of RBC is known as agglutination.

Genotype of ABO Blood Group
In 1925 Berstein explained the genetic basis of ABO system. Blood group is controlled by autosomal single polymorphic gene I on chromosome. The gene locus (place) is represented by the symbol I (which stands for isohaemagglutinogen). There are three alleles represented by the symbol A, B (these letters refer to two carbohydrates designated A and B which are found on the surface of RBC) and i. The alleles A and B are equally dominant so they are called co-dominant and i is recessive to both A and B.

The genotype I^i would give rise to the agglutinogen A on the red blood cell membrane and the plasma would contain agglutinin anti-B. The blood group would be A. Blood group A may be homozygous AA and heterozygous Ai. Blood group B may be heterozygous Bi, blood group AB is heterozygous AB (co-dominant). Blood group O is always homozygous ii. The four blood groups do not change during the life time of any human being.

Importance of blood group
Blood grouping is important in:
(a) Transfusion
(b) Establishment of paternity

If a person with blood group A gives blood to a person with type B there will be clumping of blood due to presence of anti A in the blood group B and the recipient will probably die. A person with blood group AB has neither anti A nor anti B plasma antibody and can safely receive A, B or O blood group. A person with blood group O has no cell antigen and can safely give blood to any of the other type. The person with blood group O is therefore known as a universal donor.

Rh Blood Group
The Rh blood group was named after the Rhesus monkey, in which it was first studied by Landsteiner in 1930’s. In humans this group includes antigens or factors called Rh factor. If Rh factor is present in the red blood cell membranes, the blood is said to be Rh positive and if the red blood cells lack Rh factor, the blood is called Rh negative.

Genes of Rh factor
Rh blood group is encoded by three genes C, D, and E. These genes occupy two tightly linked loci. D occupy one locus called locus D. The genes C and E alternatively occupy other loci. The most important of these is D locus.

Gene D
Gene D has two alleles, D and d. Gene D is completely dominant over gene d. Persons having genotype DD or Dd have Rh factor on their red blood cells and are Rh positive. Persons with genotype dd do not have Rh factor and are Rh negative.

Antibody against Rh antigen
This antibody is not present in the ABO blood groups. It is only formed when Rh antigen comes in contact with A/B/AB/O blood groups. So the blood of the Rh negative person contains neither Rh antigen on its cells or Rh antibody in plasma. If the Rh negative person is given Rh positive blood, it will stimulate the plasma to produce antibody. If the same Rh negative person is given Rh positive blood, the antibody already formed in the plasma against Rh positive will react with donated blood. The person can even die. So for the transfusion of the blood, not only blood group A, AB, B, O is matched but the Rh factor is also matched i.e. Rh positive blood can be given only to Rh positive person and Rh negative blood can be given only to Rh negative person. So ABO blood group is written as:

Erythroblastosis Fetalis
The Rh factor is particularly important during pregnancy. Rh positive is dominant over Rh negative. If the mother is Rh negative (dd) and father's genotype is DD, all the offspring (Dd) will be Rh positive.
DD (Father) x dd (mother) = Dd (child)
If the father is heterozygous (Dd) the child has a fifty percent chance of being Rh positive.
Dd (father) x dd (mother) = Dd, Dd, dd, dd (child)
The red blood cells of an Rh+ child will leak across the placental barrier into the mother's circulatory system because placental tissues normally break down before and at birth. The presence of these Rh antigens causes the mother to produce anti- Rh antibodies. In this or a subsequent pregnancy with an Rh-positive baby, anti-Rh antibodies produced by the mother may cross the placenta and destroy this child's red blood cells. This is called hemolytic disease of the now born or erythroblastosis fetalis. This anemia may lead to abortion or still birth. Even if the pregnancy continues, the liver and spleen of the fetus swell as they rapidly produce red blood cells. The breakdown product is called bilirubin. Haemolysis continues after the baby is born. Due to red blood cell destruction followed by haeme breakdown, bilirubin rises in the blood. Excess bilirubin can lead to brain damage, mental retardation, jaundice and even death.
Haemolytic disease of the new born
Prevention: The problem has been solved by giving Rh- negative women an Rh immunoglobin injection either midway through the first pregnancy or no later than 72 hours after giving birth to an Rh-positive child. This injection contains anti-Rh antibodies that attack any of the baby's red blood cells in the mother's blood before these cells stimulate her immune system to produce her own antibodies. This injection is not beneficial if the woman has already begun to produce antibodies, therefore, the timing of the injection is most important.

Test of Rh factor: To test if an individual is Rh negative or Rh positive blood is mixed with an anti Rh antibodies. When Rh-positive blood is mixed with anti-Rh antibodies, agglutination occurs.

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Multiple Alleles

Many traits (characteristics) are controlled by more than two alleles. However, usually only two alleles are present at a time. The two alleles act together to produce the trait in any organism. There are many examples of multiple alleles: Different coat color in rabbit, (b) Blood group, etc.

Dominance Relations

There are four types of dominance relations among alleles:

(A)   Complete Dominance     
(B)   Incomplete Dominance
(C)   Co-Dominance
(D)   Over-Dominance

Complete Dominance
When one allele is completely dominant over the other, presence of recessive allele is functionally hidden. It is seen in heterozygous condition. We have already seen that round allele (R) is completely dominant over wrinkle allele (r) in heterozygous (Rr) condition in the F1 generation and all the contrasting pairs of alleles for all the seven characters selected by Mendel. Many breeding experiments have produced novel phenotypes and phenotypic ratio that cannot be explained on the basis of complete dominance.

Incomplete Dominance
In 1899 Carl Correns was working on four O'clock plant. In a cross between a true breeding, red flowered four o’clock and a true breeding white flowered strain, the offspring have pinks flowers. If these F1 plants self-pollinate, the F2 generation has a phenotypic ratio of 1 red flowered: 2 pink flowered: 1 white flowered plant. The heterozygous condition for particular allele can give rise to a phenotype intermediate between the dominant and recessive trait e.g. in which neither allele is dominant it is called incomplete dominance.
Incomplete Dominance

When both the alleles are fully expressed in heterozygous condition it is called co-dominance. Examples are human blood group AB and MN. Human blood groups are of many types e.g. ABO, MN, MNSs, Rh etc. Landsteiner and Levine discovered MN blood types in man on the basis of specific antigens present on RBC. There are three general phenotypes, M,N and MN. M phenotypes have antigen M which is produced by gene LM. N phenotypes have antigen N that is produced by its allele LN. MN phenotype has both M and N antigen, simultaneously produced by their alleles LM and LN. If a man having M blood marries a woman of N blood group, all their children will have MN blood group.

Over Dominance

In over dominance relation, the over dominant heterozygote exceeds in quantity to the phenotypic expression of both the homozygotes. In Drosophila the heterozygote (w+w) has more quantity of fluorescein pigments in eye than wild (w+w+) or white eyed (ww) homozygotes.