Mendelian Genetics

Extensions of Mendelian Inheritance

1. Alleles’  interaction
2. Pleiotropism
3. Epistasis interaction
4. Linkage and crossing over

Alleles’ interaction

1. Incomplete dominance
2. Lethal allele
3. Co dominant allele
4. Multiple allele
5. Penetrance and expressivity

Epistastic interaction

1. Complementary gene (9:7)
2. Duplicate gene (15:1)
3. Suppressor gene (13:3)
4. Additive gene (9:6:1)
5. Dominant epistasis (12:3:1)
6. Recessive epistasis (9:3:4)

Alleles’ interaction

1. Incomplete dominance

Alleles which lack of dominant and recessive relationship called as incomplete domninant. It means each allele capable of exerting same degree of expression in heterozygous condition.

Example: 4O’ clock plant (Mirabilis jalapa) has alleles for the red and white flowers. But neither of these colours is dominant. It appears that the parental genes blended together to form an intermediate colour (Pink). Incomplete of two alleles result in the possibility of three different phenotypes. If heterozygous pink colour allows to self pollination the colours, red and white return in the offspring.

2.Lethal allele

The phenotypic manifestation of some genes when present in an organism causes death during early stage of development (before sexual maturation) and such genes called as lethal allele. A fully dominant lethal allele (That is one that kills in both the homozygous and heterozygous condition) occasionally arise by mutation from a wild type allele. In sometimes dominant lethal genes are lost from the heterozygous organism called as gene erosion. Most of all lethal genes are recessive; it expresses or causes death of the organism only when they are homozygous. They are present in the population in heterozygous condition and become homozygous when two carriers are cross together. There are two types of lethal allele.

A.One that has no obvious phenotypic effect in heterozygous.

a.Mice coat colour

In mice, yellow coat colour is produced by a dominant allele Y and while it’s recessive allele y determines the normal grey coat colour. Further all, the mice with yellow coat colour is heterozygous (Yy). Alleles present in dominant homozygous condition cause death in embryo.

b.Aurea gene produces yellow leaved (due to lack of chlorophyll) in the heterozygous state in Antirrhinum majus).

c.Dexter gene in cattle

d.Achondroplastic dwarfness in man.

B.One that exhibit a distinctive phenotype when heterozygous.

The amount of chlorophyll in snapdragons is controlled by a pair of alleles C¹ and C². One of which C² exhibits lethal effect when homozygous and a distinctive colour phenotype when heterozygous. Thus, with regard to colour, these alleles are incomplete dominant. However, with regard to viability the C² allele is fully recessive; that is the C₂ allele only causes death when C¹ is absent.

Phenotypic ratio:
Green (C¹C¹): Pale green (C¹C²): White (C²C²)= 2:1

 Lethal

3.Co – dominant allele

Alleles that lack of dominant and recessive relationships and are both observed phenotypically to some degree are co-dominant. This means that the phenotypic effect of each allele is observable in heterozygous condition. Hence, the heterozygous genotype gives rise to a phenotype distinctly different from either of the homozygous genotype, but possesses characteristics of each other. For co-dominant alleles all uppercase base symbols with different superscripts are used.

4.Multiple allele

The genetic systems proposed thus far have been limited to a single pair of alleles. The maximum number of alleles at a gene locus that any individual possesses is two with one on each of the homologous chromosomes. But since a gene can be changed to alternative forms by process of mutation, large number alleles are theoretically possible in a population of individuals. Whenever more than two alleles are identified at a gene locus in a population, such alleles are called multiple allele and the series called multiple allele series. These alleles may have arisen as a result of mutation of the dominant (wild) allele in a gene pair. 

The common characters of multiple allele are;

1. They occupy same locus within the homologous chromosomes.In a diploid cell any two alleles of such allele series are present in a pair of homologous chromosomes. The gamete of an organism contains only one allele of such series.
2. Multiple allele controls the particular character but with varying degree of efficiency.
3. The normal gene of the series act as dominant overall such series alleles may also behave as dominant, recessive and co-dominant among them.
4. The capital letter is commonly used to designate allele that is dominant to all others in the series. The corresponding lower case letter designates the allele that is recessive to all others in the series. Other alleles, intermediate in their degree of dominance between these two extremes, are usually assigned the uppercase letter with some suitable superscript.
   Examples:

a.Eye colour of Drosophila

b.Coat colour in rabbit

c.Blood group in man

d.Self sterility genes in plants. Eg: Red clove and Tobacco.

5.Penetrance and expressivity

Differences in environmental condition/ in genetic backgrounds may cause individuals that are genetically identical at a particular locus to exhibit different phenotypes. The percentage of individuals with a particular gene combination that exhibit the corresponding character to any degree represents the penetrance of the trait.

The polydactyl (extra fingers and or toes) in human can be produced by a dominant gene P. The wild type condition with five digits on each limb is produced by the recessive gene p. However, some heterozygous individuals (Pp) are not polydactylous. If 20% of Pp individuals do not show polydactyl (that are wild type) the gene has a penetrance of 80%. A trait although penetrant may be quite variable in its level of expression. The degree of effect produce by a penetrant genotype is term expressivity.

Pleiotropism

A gene that has multiple phenotypic effects is called Pleiotropism. It is a special interest because it helps in understanding the relationships between different organs of the same individuals.

Examples:

1. Drosophilabar eyed individuals may be significantly altered by the wing nature.
2. Seed coat colour gene of sweet pea controls flower colour and also red spot in leaf axils
3. Sickle cell anemia in human.

Exceptions of mendelian laws

I. Incomplete dominance / Codominance: (example: blood type)

One example of a three-allele gene: the ABO blood types of humans: In this case BOTH the IA (A) and IB (B) gene are dominant and are expressed in the phenotype. The recessive gene i is only seen in the phenotype (Type O) if the parents are heterozygotes or are Type O themselves.

IA : Allele for Type A blood

IB : Allele for Type B blood

i : Allele for Type O blood

 

If you have Type A blood, you are either IA IA or IA i

If you have Type B blood, you are either IB IB or IB i

If you have Type O blood, you are ii (only choice!)

If you have Type AB blood, you are IA IB (only choice!)

Note that the IA and IB alleles two alleles are both dominant to i – but one isn’t dominant over another. This is called Incomplete Dominance or Codominance

II. Pleiotropy: One gene defect results in many widespread effects on the body because the gene product (protein) is something that used throughout the body

Example: Sickle cell disease – one defect in the hemoglobin gene – a single amino acid change in the protein – has many widespread and devistating effects.

1.pain episodes
2.strokes
3.increased infections
4.leg ulcers
5.bone damage
6.yellow eyes or jaundice
7.early gallstones
8.lung blockage
9.kidney damage and loss of body water in urine
10.painful erections in men (priapism)
11.blood blockage in the spleen or liver (sequestration)
12.eye damage
13.low red blood cell counts (anemia)

Over 2.5 million Americans are carriers (heterozygotes) for the disease, and 70,000 have sickle cell disease. The disease is very common in people of recent African descent, because in areas of the world where malaria in prevalent, being a carrier for SSD provides a selective advantage against developing malaria!

“T” (Tionne Watkins), of the grammy-award winning group TLC, has sickle cell disease and is the National Celebrity Spokeswoman for the Sickle Cell Disease Association of America, (SCDAA)

Another example: Marfan’s syndrome – individuals have defects in skeletal system, eyes, and cardiovascular system. All these defects are due to one underlying defect – the body’s ability to make connective tissue – one defect has widespread implications in the body

• Abraham Lincoln may have had Marfan’s syndrome.
• Many times an Marfan’s disease can be fatal to athletes, such as volleyball player Flo Hyman

III. Epistatic (“covering up”) genes : An epistatic gene interferes with the expression of another, perfectly functional, gene (example: Coat color in Laborador Retreivers, Albinism).

The gene E is involved the ability of the coat to contain pigments like black or brown. If the dogs are EE or Ee, the coat will appear black (BB or Bb) or brown [‘chocolate’] (bb). BUT, if this gene is found in the homozygous recessive condition, ee, there will be no coat color, regardless of what the B alleles are! (BB, Bb, or bb). The result is a ‘yellow’ or ‘golden lab:

Golden lab: eeBB, eeBb, or eebb

Black lab: EEBB, EeBB, EEBb, EeBb

Chocolate lab: EEbb or Eebb

Thus, it doesn’t matter what the black or brown coat color alleles are, the E gene is epistatic to this gene and can cover up the expression of these traits if heterozygous recessive. (We will work this problem out in class)

Another example – Albinism in humans. Individuals with this trait lack pigment (melanin) in all parts of their body, even though they have inherited alleles for skin color, eye color, and hair color. elanin is a dark brown pigment normally present in the human skin, hair, and eyes. Albinism arises from a genetic
defect resulting in the tyrosinase gene, which produces an enzyme necessary for the melanin synthesis. production of melanin. Generalized albinism occurs in all races in about one in 20,000 persons.
If a person inherits a double dose of the allele for albinism (aa), they will be unable to produce the pigment melanin, regardless what color their alleles for eye, skin, and hair color are.

IV. Continuous Variation: Mendel studied “either-or” traits (purple vs white), but many characters such as human height and skin color vary as a continuum in populations (bell shaped curve)

1. Modifier genes: (example: eye color) Eye color is not a simple trait controlled by different alleles of one gene. Rather, eye color in controlled by at least 3 genes: EYCL, the Green/blue eye color gene (probably located on chromosome 19); EYCL2, the central brown eye color gene (possibly located on chromosome 15), and EYCL3 , the Brown/blue eye color gene located on chromosome 15. These three genes contribute to the typical patterns of inheritance of brown, green, and blue eye colors

For EYCL3, B = brown or b = blue eyes. However,grey eye color, hazel eye color, and multiple shades of blue, brown, green, and grey come from the ccombined action of all three genes PLUS the action of modifier genes that control how much pigment is deposited in the iris of the eye.

2. Polygenic Inheritance: (example: human height) more than one gene controls a particular phenotype

In polygenic inheritance, more than one gene controls a particular phenotype. ie skin color is thought to be controlled by 3 alleles (A, B, C).

A person with the alleles AABBCC is very dark skinned, a person with aabbcc alleles is very light skinned, and a person with AaBbCc (or any combo) has an intermediate skin color.

Different “units” produce different shades (AAbbCc, aaBbcC, etc…)