Extra Mendelian inheritance - Incomplete and Co dominance, Multiple alleles, Lethal genes, Epistasis, Pleiotropy

Aneuploidy and Polyploidy

 

Aneuploidy and polyploidy are chromosomal abnormalities involving changes in chromosome number. Aneuploidy is the loss or gain of one or more individual chromosomes (e.g.,  2n-1 or 2n+1) often causing human genetic disorders like Down syndrome. Polyploidy is the addition of entire extra sets of chromosomes (3n, 4n etc.) which is common in plants but usually lethal in animals.

 Aneuploidy involves an abnormal number of specific chromosomes, while polyploidy involves extra sets of chromosomes. Aneuploidy is common in human genetic disorders and cancers. Polyploidy is rare in humans but widespread and often beneficial in plants (e.g., wheat).

 Aneuploidy usually results from non-disjunction during meiosis. Polyploidy results from the failure of cytokinesis following nuclear division (karyokinesis), producing cells with multiple sets, common in plant

 Aneuploidy: Monosomy (2n-1) Trisomy (2n+1) Nullisomy (2n-2) Examples in Humans: Down syndrome (Trisomy 21), Turner syndrome (45 XO)), Klinefelter syndrome (47 XXY)

 Polyploidy: Triploidy (3n), Tetraploidy (4n), Autopolyploidy (sets from one species), Allopolyploidy (sets from different species).

 Extra Mendelian inheritance- Alternatives to Dominance and Recessiveness

 Mendel’s experiments with pea plants suggested that:

 (1) two “units” or copies exist for every gene; alleles

(2) alleles maintain their integrity in each generation (no blending); and

(3) in the presence of the dominant allele, the recessive allele is hidden and makes no contribution to the phenotype.

Therefore, recessive alleles can be “carried” and not expressed by individuals. Such heterozygous individuals are sometimes referred to as “carriers.”  Further genetic studies in other plants and animals have shown that much more complexity exists.

The alleles of the same gene interacts in such a way to produce a new character, which is known as allelic interactions.

         Incomplete Dominance 

• In incomplete dominance, neither allele is completely dominant over the other.
• The heterozygous phenotype is intermediate between the two homozygous phenotypes.
• Example: In snapdragon flowers, red (RR) and white (WW) alleles produce pink (RW) flowers. 

            Co-dominance

• In co-dominance, both alleles in the heterozygote are fully expressed.
• The phenotype shows both traits simultaneously.
• Example: Human ABO blood group system, where I^A and I^B alleles are co-dominant producing AB blood group. 

            Multiple Alleles

• More than two allelic forms exist for a gene in a population.
• An individual still carries only two alleles, but the gene has multiple variants.
• Example: ABO blood group gene has three alleles: I^A, I^B, and Iⁱ.

Lethal Alleles

• Alleles that cause death when present in homozygous condition.
• They can be dominant or recessive.
• Example: In mice, the yellow coat color allele (Y) is lethal when homozygous (YY). 

            Epistasis

• Interaction between genes where one gene masks or modifies the expression of another gene.
• It affects phenotypic ratios in dihybrid crosses.
• Example: Coat color in Labrador retrievers where one gene controls pigment color and another controls pigment deposition.

 Pleiotropy

• A single gene influences multiple, seemingly unrelated phenotypic traits.
• Example: The gene responsible for Marfan syndrome affects connective tissue, causing effects in skeleton, eyes, and cardiovascular system.

 Incomplete dominance

 Incomplete dominance is a form of gene interaction in which both alleles of a gene at a locus are partially expressed, often resulting in an intermediate or different phenotype.  It is also known as partial dominance.

• For eg, the pink color of flowers (such as snapdragons or four o'clock flowers (Mirabilis jalapa)

In incomplete dominance, the genes of an allelomorphic pair are not expressed as dominant and recessive but express themselves partially when present together in the hybrid. As a result F1 hybrids show characters intermediate to the effect of two genes of the parents. It occurs when neither of two alleles is fully dominant nor recessive towards each other. The alleles are both expressed and the phenotype, or physical trait, is a mixture of the two alleles.

In less technical terms, this means that the two possible traits are blended together.

F2 generation shows genotype ratio of 1RR:^:2Rr:1rr  and a phenotype ratio 1:2:1 red:pink:white.

 

  

    The phenotype of a heterozygous organism is a blend between the phenotypes of its homozygous parents. In the snapdragon, Antirrhinum majus, a cross between a homozygous white-flowered plant C^WC^W and a homozygous red-flowered plant C^RC^R will produce offspring with pink flowers C^RC^W. This type of relationship between alleles, with a heterozygote phenotype intermediate between the two homozygote phenotypes, is called incomplete dominance.

 

     

 

Self-fertilization of a pink plant would produce a genotype ratio of 1C^RC^R: 2 C^RC^W:1C^WC^W and a phenotype ratio 1:2:1 red:pink:white.

  Examples of incomplete dominance:

-Incomplete Dominance in Animals-

1. Chickens with blue feathers are an example of incomplete dominance. When a black and a white chicken reproduce and neither allele is completely dominant, the result is a blue-feathered bird.

2. When a long-furred Angora rabbit and a short-furred Rex rabbit reproduce, the result can be a rabbit with fur longer than a Rex, but shorter than an Angora. That's a classic example of incomplete dominance producing a trait 1different from either of the parents. 

-Incomplete Dominance in Plants-

1. Wild four-o-clocks tend to have red flowers, while "pure" four-o-clocks with no coloration genes are white. Mixing the two results in pink flowers which are a result of incomplete dominance. However, mixing the pink flowers results in 1⁄4 red, 1⁄4 white and 1⁄2 pink. That 1:2:1 ratio - a quarter like one parent, a quarter like the other, and the remaining half different from either - is common in cases of incomplete dominance.

2. The fruit color of eggplants is another example of incomplete dominance. Crossing deep purple eggplants with white eggplants results in eggplants of a light violet color.

-Incomplete Dominance in Humans- 

 Incomplete dominance is rare in humans; we're genetically complex and most of our traits come from multiple genes. However, there are a few examples

1. When one parent with straight hair and one with curly hair have a child with wavy hair, that's an example of incomplete dominance.

2. Eye color is often cited as an example of incomplete dominance. In fact, it's a little more complicated than that, but hazel eyes are partially caused by incomplete dominance of multiple genes related to green and brown eye color.

3. The disease familial hypercholesterolemia (FH) is an example of incomplete dominance. One allele causes liver cells to be generated without cholesterol receptors, while another causes them to be generated normally. The incomplete dominance causes the generation of cells that do not have enough receptors to remove all dangerous cholesterol from the bloodstream.

Codominance 

A condition in which both alleles of a gene pair in a heterozygote are fully expressed. Thus, Codominance, is where both alleles are simultaneously expressed in the heterozygote. As a result, the phenotype of the offspring is a combination of the phenotype of the parents. Thus, the trait is neither dominant nor recessive.

 

1.   Individuals with type AB blood.

The best example of co-dominance is ABO blood group. ABO blood grouping is controlled by gene I which has three alleles A, B, and O and show co-dominance. An O allele is recessive to both A and B. The A and B alleles are co-dominant with each other. When a person has both A and B, they have type AB blood. Thus, a person  inheriting the alleles A and B alleles will have a type AB blood because A and B alleles  are co-dominant and therefore will be expressed together.

Other co-dominance examples are the white-spotted red flower in plants and the black-and-white- coated mammals.

    

 

In co-dominance, it does not matter whether the alleles in the homologous chromosomes are dominant or recessive. If the homologous chromosome consists of two alleles that can produce proteins, then both will be produced and forms a different phenotype or characteristics to that of a homozygote.

Co-dominance vs polygenic inheritance –Co-dominance is a different concept from polygenic inheritance. While both of them do not conform to the Mendelian inheritance, they differ in a way that in polygenic inheritance multiple genes are involved to produce cumulative effects. In codominance, different alleles of a single gene affect the resulting trait. Examples of polygenic traits in humans are height, weight, skin color, and eye color.

 

2.     MN blood groups of humans

A person's MN blood type is determined by his or her alleles of a certain gene. An L^M allele specifies production of an M marker displayed on the surface of red blood cells, while an L^N allele specifies production of N marker. Homozygotes L^ML^M and L^NL^N have only M or an N markers, respectively, on the surface of their red blood cells. However, heterozygotes L^ML^N have both types of markers in equal numbers on the cell surface. 

Mendel's rules can predict inheritance of codominant alleles. For example, if two people with L^ML^N genotypes had children, there would be M, MN, and N blood types and L^ML^M,  L^ML^N  and L^NL^N genotypes in their children in a 1:2:1 ratio.

 

Question

Multiple alleles 

More than two alleles of the same gene are present in the population.  

(1) Human Blood Group 

The human ABO blood type is a good example of multiple alleles.

 

     Mendel's work suggested that just two alleles existed for each gene. Although individual humans (and all diploid organisms) can only have two alleles for a given gene, multiple alleles may exist in a population level, and different individuals in the population may have different pairs of these alleles.

(2) Coat color in rabbits

     A gene that specifies coat color in rabbits, called the C gene comes in four common alleles: C, ch, h, and c

• A CC rabbit has black or brown fur
• A C^chC^ch rabbit has chinchilla coloration (grayish fur).
• A C^hC^h rabbit has Himalayan (color-point) patterning, with a white body and dark ears, face, feet, and tail
• A C^cC^c rabbit is albino, with a pure hite coat.

 Multiple alleles makes for many possible dominance relationships. In this case, the black CC allele is completely dominant to all the others; the chinchilla C^chC^ch allele is incompletely dominant to the Himalayan C^hC^h and C^cC^c albino  alleles and the Himalayan C^hC^h allele is completely dominant to the albino C^cC^c allele.

Rabbit breeders figured out these relationships by crossing different rabbits of different genotypes and observing the phenotypes of the heterozygous kits (baby bunnies)

Lethal genes 

Lethal gens/alleles, cause the death of the organism that carries them. They are usually a result of mutations in genes that are essential for growth or development. Lethal alleles may be recessive, dominant, or conditional depending on the gene or genes involved. Lethal alleles were first discovered by Lucien Cuénot in 1905 while studying the inheritance of coat color in mice.

Lethal alleles can cause death of an organism prenatally or any time after birth, though they commonly manifest early in development. 

 Types of lethal allele

 There are basically three types of lethal genes present depending on the gene or genes involved. They are:

 · Recessive lethal- A pair of identical alleles that are present in an organism and ultimately results in death of that organism are referred to as recessive lethal alleles. Recessive lethal are only fatal in the homozygous condition. Heterozygotes will sometimes display a form of diseased phenotype. One mutant lethal allele can be tolerated, but having two results in death. 

 TaySach's lethal

Tay-Sachs disease is a fatal, inherited neurodegenerative disorder caused by a mutation in the HEXA gene, leading to toxic, fatal accumulation of fat (GM2 ganglioside) in nerve cells. Infantile Tay-Sachs, the most common form, appears around 3–6 months, causing rapid regression, blindness, and paralysis, typically resulting in death by age 4 or 5. It is an autosomal recessive disorder, meaning a child must inherit two copies of the mutated gene (one from each parent) to be affected.

 · Dominant lethal- When only one copy of allele is present in an organism is fatal, is known as dominant lethal alleles. These alleles are not commonly found in populations because they usually result in the death of an organism before it can transmit its lethal allele on to its offspring. An example shown in humans of a dominant lethal allele is Huntington's disease, a rare neurodegenerative disorder that ultimately results in death. A person exhibits Huntington's disease when they carry a single copy of Huntington allele on chromosome 4.

Yellow lethal in mice

In 1905, French geneticist Lucien Cuénot discovered that the yellow coat color in mice is a dominant trait that is lethal in the homozygous state (YY). While yellow mice are heterozygous (Yy) survive, homozygous yellow mice die early in embryonic development, causing a 2:1 ratio of yellow to non-yellow offspring in crosses. 

Dominant Phenotype: The yellow allele (Y) is dominant for coat color, as even a single copy produces a yellow coat.

Recessive Lethality: The  allele is recessive regarding lethality; only mice with two copies (YY) die.

2:1 Ratio: Crossing two yellow mice (Yy) consistently produces a 2:1 ratio of yellow to agouti (grey) offspring, not the expected 3:1 Mendelian ratio.

 · Conditional lethal- Alleles that will only be fatal in response to some environmental factor are referred to as conditional lethals. One example of a conditional lethal is favism, a sex-linked inherited condition that causes the carrier to develop hemolytic anemia when they eat fava beans 

EPISTASIS 

In epistasis, the interaction between two genes is antagonistic, such that one gene masks or interferes with the expression of another. “Epistasis” is a word composed of Greek roots that mean “standing upon.” The alleles that are being masked or silenced are said to be hypostatic to the epistatic alleles that are doing the masking. Often the biochemical basis of epistasis is a gene pathway in which the expression of one gene is dependent on the function of a gene that precedes or follows it in the pathway.

 The phenomena where the effect of one gene depends on the presence of one or more gene, is known as epistasis. The phenotypic effect of one gene is masked by another gene. The gene which masks the effect of another gene is known as epistatic gene. The epistatic genes can be dominant or recessive in their effects and the gene whose effect is masked by the epistatic gene is known as hypostatic gene.

By the definition, confusion arises between the dominance and epistasis but dominance involves intra-allelic gene interaction and one allele hides the effect of other allele at the same gene pair, whereas in epistasis it involves inter-allelic gene interaction i.e. one gene hides the effect of other gene at other gene loci.

For the study of linkage association analysis, epistasis plays an important role. Epistatic mutations therefore have different effects on their own than when they occur together. Epistasis has a great influence on the evolvability of phenotypic traits.

 

TYPES OF EPISTASIS

 Dominant Epistasis When a dominant allele hides the effect of allele of another gene and expresses and itself phenotypically, is known as the dominant epistasis. The hypostatic allele will only get expressed when the gene locus contains two recessive alleles. The expression of one dominant or recessive allele is masked by another dominant gene. This is also referred to as simple epistasis.

An example of dominant epistasis is found for fruit colour in summer squash. There are three types of fruit colors - white, yellow and green. White colour is controlled by dominant gene W and yellow colour by dominant gene G. White is dominant over both yellow and green. The green fruits are produced in recessive condition (wwgg). 

A cross between plants having white and yellow fruits produced F1 with white fruits. Intermating of F1 plants produced plants with white, yellow and green coloured fruits in F2 in 12:3:1 ratio.

FIG- The figure explains the dominant epistasis for fruit colour in summer squash. The normal dihybrid modified to12:3:1 in F2 generation. Here W is dominant to w and epistatic to alleles G and g. Hence it will mask the expression of G/g alleles. Hence in F2, plants with W-G-(9/16) and W-gg (3/16) genotypes will produce white fruits; plants with wwG-(3/16) will produce yellow fruits and those with wwgg (1/16) genotype will produce green fruits. Thus the normal dihybrid ratio 9:3:3:1 is modified to 12:3: 1 ratio in F2 generation.

Similar type of gene interaction has been reported for skin color in mice and seed coat color in barley.

 Recessive Epistasis

The recessive allele of one gene locus hides the effect of another gene locus and expresses itself phenotypically. When recessive alleles at one locus mask the expression of both (dominant and recessive) alleles at another locus, it is known as recessive epistasis.

An example of recessive epistasis is pigmentation in mice. The wild-type coat color, agouti (AA), is dominant to solid-colored fur (aa). However, a separate gene (C) is necessary for pigment production. A mouse with a recessive c allele at this locus is unable to produce pigment and is albino regardless of the allele present at locus A (Figure 1). Therefore, the genotypes AAcc, Aacc, and aacc all produce the same albino phenotype. A cross between heterozygotes for both genes (AaCc x AaCc) would generate offspring with a phenotypic ratio of 9 agouti:3 solid color:4 albino. 

In this case, the c gene is epistatic to the A gene.

 

 

A-C-  agouti          A-C- Black                A-cc white

Another good example of such gene interaction is found for grain colour in maize. There are three colours of grain in maize, viz., purple, red and white. The purple colour develops in the presence of two dominant genes (R and P), red colour in the presence of a dominant gene R, and white in homozygous recessive condition (rrpp). A cross between purple (RRPP) and white (rrpp) grain colour strains of maize produced plants with purple colour in F1. Inter-mating of these F1 plants produced progeny with purple, red and white grains in F2 in the ratio of 9:3:4.

 Recessive epistasis for grain colour in maize.    RRPP x rrpp

The normal dihybrid segregation ratio 9:3:3:1 is modified to 9:3:4 in F2 generation. Here allele r is recessive to R, but epistatic to alleles P and p. In F2, all plants with R-P-(9/16) will have purple grains and those with R-pp genotypes (3/16) have red grain color. The epistatic allele r in homozygous condition will produce plants with white grains from rrP-(3/16) and rrpp (1/16) genotypes. Thus, the normal segregation ratio of 9:3:3:1 is modified to 9:3:4 in F2 generation.

 Such type of gene interaction is also found for coat color in mice, bulb color in onion and for certain characters in many other organisms.

 

Pleiotropism

 Pleiotropism is the condition in which a single gene controls more than one phenotypic effect, that is completely unrelated.  Pleiotropy is a condition in which a single gene has multiple phenotypic expressions.

E.g.: Phenylketonuria It is an autosomal recessive disorder due to problem in chromosome number 12 

When the phenylalanine levels are affected, it causes a disease known as phenylketonuria- due to the defect in single gene present on chromosome 12 which codes for the phenylalanine hydroxylase. Phenylalanine is an essential amino acid obtained from food and causes multiple effects such as mental retardation, hypopigmentation of hair and skin.

 

 Other examples of the pleiotropy are albinism, sickle cell anemia, autism, etc. Pleitropy not only affects humans but also its affect is seen in the animals as well like, chicken, mice, etc.

• Sickle cell disease is caused by a problem in the hemoglobin-beta gene found on chromosome 11. The defect forms abnormal hemoglobin.