UNIT 1 – Mendel's Laws (Q&A) | MZO-002 MSCZOO | IGNOU

SAQ 1

Fill in the blanks

a) The title of the paper presented by Mendel in 1866 is ......................... .

Answer: Experiments in Plant Hybridization

b) The term 'genetics' was coined by ........................ .

Answer: William Bateson

c) Mendel proposed the concept of ...................... units.

Answer: hereditary 

d) Mendel's work was rediscovered by ........................., ........................... and .......................... .

Answer: Carl Correns, Hugo de Vries and Erich von Tschermak

SAQ 2

Answer in one word.

a) In Mendelian crosses, progeny is produced from the mating of individuals in the parental generation.

Answer: first filial generation or F1

b) The factors that regulate the inheritance of traits and act like discrete particles that remain separate.

Answer: hereditary factors (genes)

c) A genetic cross involving a single (mono) trait.

Answer: monohybrid cross

d) A trait/factor that remains hidden and not fully expressed in the progeny.

Answer: recessive

e) The process of separation of alleles.

Answer: segregation 

SAQ 3

State whether the statements are True (T) or False (F):

a) Theodor Boveri observed that the embryonic development of sea urchins was independent of the presence of chromosomes.

Answer: False

b) Mendel's laws supported the chromosomal theory of inheritance and correlation.

Answer: True

c) Male and female gametes had different numbers of chromosomes.

Answer: False

d) A cross involving plants differing in three contrasting traits is a trihybrid cross.

Answer: True

e) Chi-square analysis is used by geneticists to evaluate whether a deviation in genetic data from expected results is due to chance or some other factor like linkage, or selection.

Answer: True

f) A cross between a homozygous dominant tall pea plant and a heterozygous tall pea plant yields 100% tall pea plants.

Answer: True

SAQ 4

Match the items given in column A with those given in column B.

Answer: a) → iii),     b) → v),     c) → i),     d) → iv),     e) → ii)

SAQ 5

State whether the following statements are True (T) or False (F):

a) A person having blood group B can receive blood from donors who are blood type B and AB.

Answer: False

b) When type A blood is mixed with type AB blood, agglutination occurs.

Answer: True

c) Blood group of Mr. X is 'A' and the blood group of Mrs. Y is 'B', therefore all their children will have blood type 'AB'.

Answer: False

d) Sickle cell disease exemplifies codominance.

Answer: True

e) Pollen bearing S₁ allele will be able to fertilize stigma having S₁S2 alleles.

Answer: False

f) Chickens showing creeper traits are homozygotes.

Answer: False

g) Rh-negative mothers can never have Rh-positive children.

Answer: False

h) Favism is a conditional lethal.

Answer: True

i) Tay-Sachs disease exemplifies incomplete dominance.

Answer: True

TERMINAL QUESTIONS

1. What is a testcross and why is it done?

A testcross is a type of genetic cross used in Mendelian genetics to determine the genotype of an individual that shows a dominant phenotype. The outward appearance (phenotype) of an organism may not always reveal its exact genetic composition (genotype), especially when dominant traits are involved. An organism showing a dominant trait may be homozygous dominant (AA) or heterozygous (Aa). A testcross helps to find out which of the two genotypes is present.

In a testcross, the individual showing the dominant phenotype is crossed with a homozygous recessive (aa) individual. Since the genotype of the recessive parent is known, the pattern of offspring obtained from this cross can help in determining the unknown genotype of the dominant parent.

Gregor Mendel first used this technique in his pea plant experiments. For example, if a tall pea plant, which could be either TT or Tt is crossed with a dwarf plant (tt), the resulting offspring will help in identifying the genotype of the tall plant.

• If all the offspring are tall, the parent is likely TT.
• If the offspring show a 1:1 ratio of tall and dwarf, the parent is Tt.

This method is important because direct observation cannot reveal whether a dominant-looking individual carries a recessive allele. In experimental genetics, such information is very useful to select and maintain pure lines or hybrids depending on the aim of the study.

Testcrosses are widely used in modern genetics, especially in plant breeding, animal breeding and laboratory model organisms like fruit flies (Drosophila) and mice, to analyze inheritance patterns and to build linkage maps. It is a very simple but powerful tool to study gene transmission, especially in controlled genetic experiments.

Why is a Testcross Done?

A testcross is performed mainly for the following purposes:

1. To determine the unknown genotype:

The main use of a testcross is to identify whether an individual with a dominant phenotype is homozygous dominant (AA) or heterozygous (Aa). This is done by crossing it with a homozygous recessive (aa) individual.

• If all offspring show the dominant trait, the unknown parent is likely homozygous (TT).

• If half show dominant and half show recessive traits, then the unknown parent is heterozygous (Tt).

2. For breeding and pure line development:

In plant or animal breeding, breeders want to select only true-breeding individuals. A testcross helps confirm whether the individual will pass on the dominant trait to all offspring, which is essential in producing stable varieties.

3. For gene linkage and gene mapping studies:

When multiple genes are involved, testcrosses are used to study how genes are inherited together, also known as linkage. It helps geneticists find the distance between genes on a chromosome by calculating recombination frequency.

2. What are the salient features of the chromosomal theory of inheritance?

The Chromosomal Theory of Inheritance, proposed by Walter Sutton (1902) and Theodor Boveri (1902–1903), explains that genes are carried on chromosomes and their behaviour during meiosis directly relates to Mendel's laws of inheritance. The following are its main features:

1. Chromosomes are the physical carriers of hereditary information:

According to this theory, genes (units of inheritance) are physically located on chromosomes. These chromosomes are passed from parents to offspring during reproduction. Each chromosome carries many genes and this explains how traits are inherited generation after generation.

2. Chromosomes occur in homologous pairs in diploid cells:

Every diploid organism has two sets of chromosomes, one set from the mother and one from the father. Each chromosome in one set has a matching partner in the other set, called its homologous pair. These homologous chromosomes carry the same type of genes but possibly different alleles.

3. Homologous chromosomes segregate during meiosis:

During the process of meiosis (specifically in Anaphase I), homologous chromosomes are separated and distributed into different gametes. This segregation of chromosomes explains Mendel's Law of Segregation, where alleles of a gene separate into different gametes.

4. Independent assortment of chromosomes explains genetic variation:

During metaphase I of meiosis, the orientation of each homologous pair is random. This means that maternal and paternal chromosomes are assorted independently into gametes. This physical basis supports Mendel's Law of Independent Assortment, leading to variation among offspring.

5. Fertilization restores the diploid condition:

When two haploid gametes (egg and sperm) fuse during fertilization, the diploid number of chromosomes is restored. This ensures that the chromosome number remains constant across generations and both parental sets contribute equally to the genetic material of the offspring.

3. Normal length of fur in rabbits is controlled by the dominant allele R, and a short type of fur called "rex" is determined by the recessive allele r. The dominant allele B is responsible for black fur colour, while the recessive allele b determines brown colour. What are phenotypic ratios resulting from a cross between a homozygous rabbit with normal length of black fur and rex rabbit with brown fur?

Genetic Information Given:

R = dominant allele for normal fur

r = recessive allele for rex fur (short fur)

B = dominant allele for black fur

b = recessive allele for brown fur

Parent Genotypes:

• Genotype of homozygous normal black fur rabbit Genotype: RRBB

• Genotype of rex brown fur rabbit (both recessive traits): rrbb

Cross:

RRBB × rrbb

By applying Mendel's Law of Independent Assortment, we make a Punnett square using gametes:

• Gametes from RRBB → Only one type: RB
• Gametes from rrbb → Only one type: rb

When crossed:

RB × rb → RrBb

So, all offspring (F1 generation) will have genotype RrBb.

Phenotype of RrBb:

Rr = expresses normal fur (R is dominant)

Bb = expresses black colour (B is dominant)

Final Phenotypic Ratio:

Since all F1 offspring have the same genotype (RrBb), the phenotypic ratio is 100% normal black fur.

4. What phenotypic classes will be obtained from a cross between AaBb × aabb? In what proportions? What is this cross called?

Parent Genotypes:

• Parent 1: AaBb
• Parent 2: aabb

Gametes Produced:

• AaBb can produce 4 types of gametes: AB, Ab, aB, ab
• aabb can only produce one type of gamete: ab

Punnett Square and Offspring Genotypes:

We now combine each gamete from AaBb with the only gamete (ab) from aabb:

Phenotypic Classes:

The phenotype of each genotype:

1. AaBb → Dominant for both traits (A- and B-)
2. Aabb → Dominant for trait A, recessive for trait B
3. aaBb → Recessive for trait A, dominant for trait B
4. aabb → Recessive for both traits

In what proportions of phenotypic ratio?

Phenotypic Ratio (Proportions):

Each combination occurs with equal probability (1 out of 4), so the phenotypic ratio is 1 : 1 : 1 : 1 (Each class appears in 25% of the offspring)

That is:

• 25% dominant for both traits (AaBb)
• 25% dominant A, recessive b (Aabb)
• 25% recessive a, dominant B (aaBb)
• 25% recessive for both traits (aabb)

What is this cross called?

This is a test cross between a dihybrid individual (AaBb) and a double recessive homozygous individual (aabb). A test cross is done to find out the genotype of an individual showing dominant traits by crossing it with an individual that is recessive for all the concerned traits.

5. What was the criticism of chromosomal theory of Sutton and Boveri? How was it resolved?

The Chromosomal Theory of Inheritance was independently proposed by Walter Sutton (1902) and Theodor Boveri (1902–1903). This theory stated that genes are physically located on chromosomes and the behavior of chromosomes during meiosis explains Mendel's laws of segregation and independent assortment.

Criticism of Chromosomal Theory of Sutton and Boveri

Although this theory provided a clear cytological basis for heredity, it initially faced several criticisms, as the scientific community was not fully convinced without direct evidence. There were three major criticisms raised against this theory:

1. Lack of Direct Evidence That Genes Located on Chromosomes

When Sutton and Boveri proposed the theory, there was no direct experimental proof showing that genes were located on chromosomes. While chromosomes could be seen under a microscope, genes were hypothetical entities at that time. Critics argued that just because chromosomes and genes behave similarly during meiosis does not mean they are the same. This criticism focused on the lack of physical or molecular linkage between genes and chromosomes.

2. Number of Genes v/s Number of Chromosomes

Another major concern was the huge mismatch between the number of traits (genes) and the number of chromosomes. For example, Mendel had described several independent traits, and in humans and many organisms, thousands of traits were known. But the total number of chromosomes was very small (e.g., only 4 pairs in Drosophila, 23 pairs in humans). Critics asked, how can so many genes be accommodated on such few chromosomes? This created doubt whether chromosomes could really carry all genetic material.

3. Contradiction with Mendel's Law of Independent Assortment

According to Mendel's second law, genes for different traits assort independently. However, if multiple genes are present on the same chromosome, they should be inherited together. At that time, the idea of linkage and recombination was not understood. So, critics asked, if genes are on chromosomes, why do they still assort independently as Mendel observed? This was seen as a contradiction between Mendel's results and chromosome behavior.

Resolution of the Criticisms

These criticisms were addressed and resolved by the pioneering work of Thomas Hunt Morgan and his students, who worked extensively on Drosophila melanogaster at Columbia University in the early 20th century.

1. Proof That Genes Are on Chromosomes

In 1910, Thomas Hunt Morgan discovered sex-linked inheritance of eye color in Drosophila. He showed that the gene for eye color was located specifically on the X chromosome, providing direct evidence that genes reside on chromosomes. This was the first experimental confirmation of the chromosomal theory.

2. Concept of Gene Linkage and Crossing Over

To explain how multiple genes on the same chromosome could sometimes assort independently, Morgan and his student Alfred Sturtevant introduced the concept of linkage and crossing over. In 1913, Sturtevant created the first genetic map of the X chromosome based on recombination frequency. He showed that genes are linearly arranged on chromosomes and during meiosis, crossing over causes exchange of segments, allowing even linked genes to segregate independently in some cases.

This answered the earlier contradiction with Mendel's law of independent assortment. It was now understood that genes far apart on the same chromosome recombine frequently, appearing to assort independently.

3. Multiple Genes per Chromosome

Once linkage maps were developed, scientists realized that each chromosome can carry many genes in linear order. So even with few chromosomes, organisms can have thousands of genes. This resolved the doubt about the limited number of chromosomes.

Final Conclusion 

• By the 1920s, the chromosomal theory of inheritance was fully accepted due to the experimental confirmation provided by Morgan and his team. The theory became the foundation of modern genetics. Every criticism that was initially raised was addressed scientifically through observations, mapping and molecular-level understanding.

6. (a) What is the difference between codominance and incomplete dominance?

In classical Mendelian genetics, traits are often explained through dominant and recessive alleles. However, in real biological systems, not all traits follow this simple rule. Two important exceptions to this pattern are codominance and incomplete dominance. These types of inheritance help explain how both alleles of a gene may influence the phenotype in different ways. Understanding the difference between them is essential in genetics, especially for interpreting traits like flower colour and human blood groups.

Codominance

Codominance is a condition where both alleles in the heterozygous condition express themselves fully and independently. In this case, the phenotype does not show blending or mixture, but rather both traits appear side by side.

A well-known example of codominance is the AB blood group in humans. A person with genotype IAIB will have both A and B antigens on the surface of red blood cells. In this case, neither the A allele nor the B allele dominates. Instead, both are fully and equally expressed. So, the blood group is not intermediate, but a co-expression of both traits.

Another example is seen in cattle coat colour. When a red-coated cow (RR) is crossed with a white-coated cow (WW), the offspring show a roan coat (RW), where both red and white patches are clearly visible on the body. These are not blended but distinctly present.

In codominance:

• Both alleles are expressed equally and independently.

• The heterozygous phenotype shows both traits clearly, without blending.

• There is no suppression of one allele by the other.

• Traits appear side by side, not as a mixture.

Incomplete Dominance

Incomplete dominance is a condition where neither of the two alleles is completely dominant over the other. As a result, the phenotype of the heterozygous individual is a blend or intermediate of both parental traits. This means that the dominant allele is not strong enough to completely suppress the expression of the recessive allele.

A very famous example of incomplete dominance is seen in the Mirabilis jalapa plant, commonly known as the four o'clock plant. When a homozygous red-flowered plant (RR) is crossed with a homozygous white-flowered plant (rr), the F₁ generation shows pink flowers (Rr). This pink colour is not present in either of the parents. It is a new phenotype formed due to the partial expression of both alleles.

In incomplete dominance:

• The heterozygous phenotype is intermediate.

• There is partial expression of both alleles.

• It creates a new blended phenotype different from both parents.

• It reduces the dominance effect and the traits appear as a mixture.

(b) How many heterozygotes and genotypes will be obtained for n number of alleles?

If there are n different alleles at a single genetic locus, then:

• Total number of genotypes = n(n + 1)/2

• Number of heterozygotes = n(n − 1)/2

7. Describe the molecular basis of multiple alleles giving a suitable example.

In classical Mendelian genetics, a gene usually has only two alleles: one dominant and one recessive. However, in real-life situations, many genes exist in more than two alternative forms. These are called multiple alleles. So, when more than two alleles exist for the same gene locus within a population, it is called the multiple allelic condition.

Although a diploid organism, like a human, carries only two alleles at a time, multiple alleles refer to the presence of more than two allelic forms in the population for the same gene. The molecular basis of multiple alleles lies in the specific changes in DNA sequence that result in structurally or functionally different proteins from the same gene

Molecular Basis of Multiple Alleles

The molecular basis of multiple alleles lies in slight differences in the DNA sequence of the gene. These mutations in the nucleotide sequence of the same gene lead to the formation of different allelic forms. These differences can be:

• A single base change (point mutation)

• An insertion or deletion of nucleotides

• Sometimes substitution of amino acids in the protein encoded.

These changes do not create entirely new genes, but they modify the gene's coding sequence, leading to the formation of functionally different proteins or enzymes from the same gene. These different versions are inherited in various combinations and result in different phenotypes.

Each allele of such a gene produces a slightly altered version of the same protein, which interacts differently with substrates or targets. Thus, the molecular variation in the gene sequence is the root cause of multiple phenotypes for a single trait.

Example: ABO Blood Group in Humans

The best example of multiple alleles in humans is the ABO blood group system, discovered by Karl Landsteiner in 1900. This trait is controlled by a single gene called single gene or I gene (isoagglutinin gene) located on chromosome number 9. This gene has three allelic forms:

1. IA allele – produces A antigen on red blood cells.
2. IB allele – produces B antigen on red blood cells.
3. i allele – produces no antigen (recessive).

At the molecular level:

• The IA and IB alleles code for slightly different glycosyltransferase enzymes that add different sugar molecules to the surface of red blood cells.

• The IA allele adds N-acetylgalactosamine, which forms the A antigen.

• The IB allele adds galactose, which forms the B antigen.

• The i allele has a mutation (frameshift), so it produces no functional enzyme and no antigen is formed.

So, the three alleles interact as follows:

• IA and IB are codominant, both are expressed when present together (as in AB blood group).

• i is recessive to both IA and IB.

Genotypes and Phenotypes in ABO System:

This system shows both codominance (IA and IB) and multiple allelism (three alleles).

8. Show the parallels between Mendelian laws and chromosomal theory of inheritance.

Gregor Mendel, in 1865, performed experiments on pea plants and explained how traits are passed from one generation to the next. He gave three important principles which are now called Mendel's Laws: Law of Dominancethe, Law of Segregation and Law of Independent Assortment. He said that traits are controlled by specific factors, which we now call genes, but he did not know where these genes are located inside the cell.

In the early 1900s, Walter Sutton and Theodor Boveri gave the Chromosomal Theory of Inheritance, which explained that genes are present on chromosomes and chromosomes behave in a special way during meiosis. The movement of chromosomes during meiosis matches exactly with what Mendel had observed in his experiments. So, this theory gave a proper physical explanation to Mendel's laws and showed how inheritance works at the cellular level.

Although the Chromosomal Theory confirmed Mendel's principles, it also added new details. For example, the theory explains the physical mechanism of segregation and independent assortment by showing how chromosomes behave during meiosis. It also clarifies why linked genes (genes on the same chromosome) may not assort independently, which Mendel's laws did not explain.

Main Parallels Between Mendelian Laws and Chromosomal Theory of Inheritance

There are three main parallels that clearly show how Mendel's laws match with chromosome behavior.

1. Law of Dominance ↔ Allelic Interaction on Chromosomes

Mendel said that when two different alleles are present together, one is dominant and its effect is seen, while the other is recessive and hidden.

Chromosomal theory supports this by explaining that dominant and recessive alleles are present on homologous chromosomes and gene expression depends on how these alleles interact inside the cell.

Note: This interaction happens on the level of DNA and proteins, though that was understood in more detail later.

2. Law of Independent Assortment ↔ Independent Assortment of Chromosomes

Mendel observed that genes for different traits are passed independently of each other, if they are not linked.

Chromosomal theory explains that during metaphase I of meiosis, different pairs of chromosomes line up and separate independently. So, genes located on different chromosomes also assort independently. However, if two genes are located on the same chromosome, they may be linked and not assort independently — this was not known to Mendel.

Note: The Chromosomal Theory adds the explanation that if genes are close together on the same chromosome, they may be linked  and not assort independently. This was not known to Mendel.

3. Law of Segregation ↔ Separation of Homologous Chromosomes in Meiosis I

Mendel said that every individual has two alleles for each gene and during gamete formation, these alleles separate, so each gamete gets only one allele.

Chromosomal theory explains this by showing that during meiosis I, the two homologous chromosomes (each with one allele) separate and go into different gametes. So, the physical separation of chromosomes supports Mendel's Law of Segregation.

Note: The difference is that Mendel saw this as an abstract principle, while Chromosomal Theory showed the actual chromosomes moving apart.

9. When a white cow was mated with a red bull, all their offspring were a mottled red and white (roan) colour. If the two roan cattle were mated, what coat colour would the progeny have and in what ratios.

This question is based on codominance, where both alleles express themselves equally in the heterozygous state. In this case, red coat and white coat are codominant traits.

Genetic Symbols Used:

• R = Allele for red coat
• W = Allele for white coat

Since both alleles are codominant, heterozygous condition (RW) shows a roan coat, which is a mix of red and white patches.

Step 1: Initial Cross

• Parent 1 (Red bull) = RR
• Parent 2 (White cow) = WW

When RR is crossed with WW:

In F₁ Generation:

• All offspring: RW (heterozygous)
• Phenotype: Roan coat (both red and white patches visible)

Step 2: Cross Between Two Roan Cattle

Now we cross two Roan (RW × RW) individuals.

Let's draw a Punnett Square for the cross:

Step 3: Resulting Genotypes and Phenotypes

From the Punnett square, we get:

• 1 RR = Red coat
• 2 RW = Roan coat (Red + White patches)
• 1 WW = White coat

Final Phenotypic Ratio:

• 25% Red (RR)
• 50% Roan (RW)
• 25% White (WW)

Thus, when two roan cattle (RW × RW) are crossed, the offspring will show:

1 Red : 2 Roan : 1 White

This is the phenotypic ratio in codominant inheritance.

10. Shown below are a series of P1 crosses and the phenotype of one of the F1 offspring. In each case, F1 offspring from two separate crosses are mated. Determine the F1 genotypes in each case. Then predict the phenotypic ratio of offspring from the mating.

a) Himalayan × Himalayan → Himalayan

      ............. × ............. → .......?......

      Full colour × Himalayan → Full colour

      ..........................................................

b) Full colour × Chinchilla → Full colour

      ............. × ............. → .......?......

      Full colour × Himalayan → Full colour

a) Himalayan × Himalayan → Himalayan

     cʰcʰ × cʰcʰ → Himalayan

     Full colour × Himalayan → Full colour

     Ccʰ × cʰcʰ → 1/2 Full colour (Ccʰ): 1/2 Himalayan (cʰcʰ)

b) Full colour × Chinchilla → Full colour

     Ccʰ × cᶜʰcᶜʰ → Full colour

     Full colour × Himalayan → Full colour

     Ccʰ × cʰcʰ → 3/4 Full colour : 1/2 Himalayan

11. Saroj who has blood group O, Rh negative, is married to Mohan who has blood group B, Rh positive and have a normal, healthy child who is O, Rh positive. They plan to have a second child. Will the couple face any problem during pregnancy? What advice can you give?

Blood Groups and Rh Factor of the Family:

• Saroj: Blood group O, Rh negative

• Mohan: Blood group B, Rh positive

• Child 1: Blood group O, Rh positive

Could there be any problem in the second pregnancy?

The main concern here is the Rh factor incompatibility between mother and child.

• Saroj is Rh negative.

• Mohan is Rh positive.

• Their first child is Rh positive (he inherited Rh+ from Mohan).

• Saroj's immune system may form antibodies against Rh+ blood cells during or after the first pregnancy. This is called Rh sensitization.

In the first pregnancy, usually, no problem occurs because the mother and baby's blood do not mix much. But during delivery, the baby's Rh+ blood can enter the mother's bloodstream. This causes Saroj to produce antibodies against Rh+ blood cells (called anti-D antibodies).

In the second pregnancy, if the baby is again Rh positive, these antibodies can cross the placenta and attack the baby's red blood cells, causing hemolytic disease of the newborn (HDN) or erythroblastosis fetalis. This is dangerous and can cause severe anemia or death of the fetus.

Will Saroj and Mohan face problems?

• Yes, there is a risk in the second and further pregnancies if the baby is Rh positive.

• The mother's anti-Rh antibodies can harm the baby.

What advice can be given?

• Saroj should get Anti-D immunoglobulin (Rhogam) injection after delivery of the first child and also during pregnancy (usually around 28 weeks). This injection prevents sensitization by destroying any Rh+ fetal cells in her blood before her immune system reacts.

• Regular monitoring of the pregnancy is needed.

• If antibodies are detected, the pregnancy must be monitored closely by a doctor.

• Blood group and Rh factor of the second baby can be tested by ultrasound or amniocentesis if needed.

12. Define lethal allele. Explain with a suitable example the molecular basis of lethality.

A lethal allele is a type of gene mutation that causes death to an organism when present in a certain genotype. Usually, lethal alleles are recessive, meaning that they cause death only when an individual inherits two copies of the lethal allele (homozygous condition). However, some lethal alleles can also act in a dominant form and cause death even when only one copy is present.

Lethal alleles generally affect essential biological processes like metabolism, development and organ formation. These alleles usually arise due to mutations that severely disrupt the function of an essential gene.

Molecular Basis of Lethality

One of the best-known classical examples of a lethal allele is found in mice involving the yellow coat color gene.

This trait is controlled by a single gene with two alleles:

• A⁺ (normal wild-type allele)
• Aʸ (mutant yellow allele)

The Aʸ allele causes yellow coat color and is dominant for this trait. But if a mouse has two copies of Aʸ (AʸAʸ), it dies early during development because this combination is lethal.

When two mice with one Aʸ allele and one normal allele (AʸA⁺) mate, the possible offspring genotypes are:

• AʸAʸ (homozygous) — these die early and do not survive

• AʸA⁺ (heterozygous) — yellow coat, healthy

• A⁺A⁺ (homozygous) — normal coat (called agouti), healthy

Normally, when two heterozygous parents mate, the expected genotypic ratio is 1:2:1 (one AʸAʸ : two AʸA⁺ : one A⁺A⁺). But since AʸAʸ individuals die, they are not counted in the living offspring.

So, the surviving offspring ratio becomes 2 yellow (AʸA⁺) : 1 agouti (A⁺A⁺).

This is why the phenotypic ratio is 2:1, not 3:1.

At the molecular level, the lethality is due to the mutation of a gene that plays a vital role in embryonic development. In this case, the Aʸ allele is linked to the Raly gene, which controls transcription of essential proteins. The yellow coat gene (Aʸ) is a result of an insertion mutation that disrupts the normal gene structure. When two Aʸ alleles are present, the gene product becomes non-functional and embryonic development fails, causing death.

Thus, the molecular basis of lethality lies in the disruption or loss of essential gene function, leading to developmental arrest or failure of vital physiological processes.

This example clearly explains both the genetic behavior and the molecular mechanism behind a lethal allele.

13. In peas, tall (T) is dominant over dwarf (t), yellow (Y) is dominant over green (y) and smooth is dominant (S) over wrinkled (s). What fraction of the offspring in the following cross would be homozygous recessive for all gene pairs in the cross: YyTtSs × Yyttss?

To solve this genetics question, we need to find what fraction of the offspring will be homozygous recessive for all three traits, that is: yy tt ss

Let us carefully break down the cross YyTtSs × Yyttss, step by step for each gene.

Step 1: Determine the gametes for each gene pair

We look at each gene separately and find out how often the homozygous recessive genotype will appear.

Gene 1: Yy × Yy

• Cross: Yy × Yy

• Possible genotypes: YY, Yy, yY, yy
• Probability of yy = 1/4

Gene 2: Tt × tt

• Cross: Tt × tt

• Possible genotypes: Tt, tt
• Probability of tt = 1/2

Gene 3: Ss × ss

• Cross: Ss × ss

• Possible genotypes: Ss, ss
• Probability of ss = 1/2

Step 2: Multiply probabilities

Now multiply the probabilities of all three homozygous recessive genotypes to get the total fraction of offspring that are yy tt ss:

1/4 yy × 1/2 tt × 1/2 ss = 1/16 yyttss

1 out of 16 offspring will be homozygous recessive (yy tt ss) for all three gene pairs.

14. Prepare a list of lethal alleles encountered in the human population and their mode of inheritance.

Lethal alleles are mutations in essential genes that can cause death either in the embryonic stage, during development, or even later in life. These alleles interfere with important cellular functions like metabolism, neural development and protein synthesis. The concept of lethal alleles was first explained by Lucien Cuenot in 1905 in mice while working on coat colour genetics. In human populations, many such lethal alleles are well documented and their modes of inheritance vary, which affects how they are transmitted from parents to offspring. These lethal genes may act in homozygous or even heterozygous conditions and can be autosomal or X-linked, depending on the location of the gene. In humans, four different types of lethal alleles are encountered, based on how they are inherited and expressed. These are described below with clear human examples.

1. Recessive Lethal Alleles (Autosomal Recessive Inheritance)

In this type, the allele causes lethality only when present in homozygous condition. If an individual inherits two copies of the mutant allele, the body fails to produce essential proteins, leading to death. However, heterozygous individuals (carriers) are usually normal or may show mild symptoms. This is the most common type of lethal allele in human populations.

Mode of inheritance: Autosomal recessive

Examples in humans:

• Tay-Sachs disease:
• Caused by a mutation in the HEXA gene, leading to the buildup of GM2 ganglioside in neurons. Infants with this condition lose motor skills, go blind and usually die by age 4.

• Cystic Fibrosis:
• Mutation in the CFTR gene leads to thick mucus formation that affects the lungs and digestive system. Without proper treatment, it can reduce life expectancy.

• Sickle Cell Anaemia (HbS/HbS):
• The homozygous condition leads to malformed red blood cells, severe anaemia and organ failure, often fatal in early life if untreated.

2. Dominant Lethal Alleles (Autosomal Dominant Inheritance)

In this type, even one copy of the mutant allele is sufficient to cause lethality. Such alleles are very rare in the population because they are naturally eliminated due to early death. However, if they allow survival until reproductive age, they can be transmitted to the next generation.

Mode of inheritance: Autosomal dominant

Examples in humans:

• Huntington's disease:
• Caused by CAG trinucleotide repeat expansion in the HTT gene. It leads to progressive brain degeneration, memory loss, mood changes and death in mid-life, typically after age 35–40, hence it can be passed on.

• Achondroplasia:
• Caused by mutation in the FGFR3 gene. Heterozygous individuals show dwarfism and survive, but the homozygous dominant (AA) condition is lethal due to improper bone development in the embryo.

3. Sub-lethal Alleles (Partial or Reduced Penetrance)

These alleles reduce survival rate or life span but do not necessarily cause immediate death. Expression can vary due to genetic background, environmental factors, or modifier genes. They are especially important in population genetics as they may appear to behave like non-lethal mutations in some individuals.

Mode of inheritance: Variable, often autosomal

Examples in humans:

• β-Thalassemia Major:
• Homozygous individuals have a complete lack of β-globin chains, requiring lifelong blood transfusions. If untreated, death occurs early in life.

• Neurofibromatosis Type I:
• Mutation in the NF1 gene causes tumour growth along nerves. Some cases may remain mild while others progress to malignant tumours, depending on penetrance and age.

4. Conditional Lethal Alleles (Environment-Dependent Expression)

These alleles become lethal only under specific environmental conditions such as exposure to certain drugs, chemicals, or dietary components. In absence of these conditions, the individuals can live a normal life. Hence, proper management can prevent lethality.

Mode of inheritance: Generally recessive; environment acts as a trigger

Examples in humans:

• G6PD Deficiency:
• Due to mutation in G6PD gene. Individuals are asymptomatic but exposure to antimalarial drugs or fava beans leads to hemolysis and potentially fatal anaemia.

• Phenylketonuria (PKU):
• Mutation in PAH gene blocks conversion of phenylalanine to tyrosine. Without a low-phenylalanine diet, brain damage and death can occur in early life.