Question

Hemophilia is an X-linked recessive mutation In humans that causes delayed blood clotting. What kinds of \(\mathrm{F}_{1}\) and \(\mathrm{F}_{2}\) offspring would be expected from matings between (a) a hemophilic female and a normal male, and (b) a hemophilic male and a normal female? Compare these results to those that would be obtained if the hemophilic gene was autosomal.

Short answer

How do these probabilities compare with autosomal inheritance? Answer: In scenario (a), all F1 offspring will either be carriers (females) or affected (males). For the F2 generation, there is a 50% chance of being affected by hemophilia or being carriers. In scenario (b), all female offspring will be carriers, and all male offspring will be normal in the F1 generation. For the F2 generation in scenario (b), 50% of the offspring will be carriers or affected by hemophilia, with equal probability for both sexes. If the hemophilic gene was autosomal, both sexes would have equal chances of inheriting the hemophilic gene, and the inheritance pattern would be the same for males and females.

Step-by-step solution

Scenario (a) - Hemophilic female and normal male

We represent the normal X chromosome with a capital X, and the X chromosome carrying the hemophilic gene with a lowercase x. So, the hemophilic female has the genotype xx, while the normal male has the genotype XY. The possible combinations of their gametes are: 1. x from female and X from male (xX) 2. x from female and Y from male (xY) Let's write down the genotypes and phenotypes of the F1 offspring: 1. xX - Carrier (female) 2. xY - Hemophilic (male) In this case, all F1 offspring will either be carriers (females) or affected (males). Now we can analyze the F2 generation. The only possible mating option is between the carrier female (xX) and hemophilic male (xY). Thus, 1. x from female and x from male (xx) 2. X from female and x from male (xX) 3. x from female and Y from male (xY) 4. X from female and Y from male (XY) The F2 offspring genotypes and phenotypes will be as follows: 1. xx - Hemophilic (female) 2. xX - Carrier (female) 3. xY - Hemophilic (male) 4. XY - Normal (male) The F2 generation will have a 50% chance of being affected by hemophilia or being carriers.

Scenario (b) - Hemophilic male and normal female

In this scenario, the hemophilic male has the genotype xY, while the normal female has the genotype XX. The possible combinations of their gametes are: 1. x from male and X from female (xX) 2. Y from male and X from female (XY) Thus, the genotypes and phenotypes of the F1 offspring are: 1. xX - Carrier (female) 2. XY - Normal (male) In this scenario, all female offspring will be carriers, and all male offspring will be normal. For the F2 generation, let's consider mating between the carrier female (xX) and normal male (XY). Their gamete combinations are: 1. x from female and X from male (xX) 2. X from female and X from male (XX) 3. x from female and Y from male (xY) 4. X from female and Y from male (XY) The F2 genotypes and phenotypes are as follows: 1. xX - Carrier (female) 2. XX - Normal (female) 3. xY - Hemophilic (male) 4. XY - Normal (male) In this case, 50% of the F2 offspring will be carriers or affected by hemophilia, with equal probability for both sexes.

Comparison with autosomal inheritance

If the hemophilic gene was autosomal, both sexes would have equal chances of inheriting the hemophilic gene, and there would be no distinction between the inheritance pattern in males and females. The F1 and F2 offspring would have the same probabilities for being hemophilic, carriers or normal, regardless of their sex.

Key concepts

X-linked Recessive Inheritance

Understanding X-linked recessive inheritance is crucial when studying conditions such as hemophilia. This pattern of inheritance involves genes located on the X chromosome. Since females have two X chromosomes (XX) and males have one X and one Y chromosome (XY), the way the gene is passed down differs greatly between the two sexes.

In the case of hemophilia, a male inheriting the mutated gene on the X chromosome will be affected because he lacks another X chromosome that could carry a normal copy of the gene. This makes the disorder more common in males. On the other hand, females must inherit two copies of the mutated gene (one from each parent) to express the condition. A female with one normal and one mutated X chromosome will be a carrier without showing symptoms.

This pattern is extremely predictable once we know the parents' genotypes. It dictates that all sons of a hemophilic mother will have hemophilia, while all daughters will be carriers, provided the father is unaffected. These rules help us understand scenarios like the ones presented in the exercise, making this concept fundamental for genetic counseling and predicting the likelihood of an inherited disorder.

Punnett Square Analysis

A Punnett square is a simple graphical way of predicting the allele combinations of offspring from parents with known genotypes. This tool is incredibly handy when examining genetic crosses, such as in the case of hemophilia.

To illustrate this, let's focus on the second scenario where a hemophilic male (xY) mates with a normal female (XX). We can represent this cross in a Punnett square, placing each parent's potential gametes on either side of the square. When these gametes combine, we get the genotypes of possible F1 offspring, which are all either carriers or unaffected. Doing a similar analysis for the F2 generation and beyond allows us to see the chances of having affected offspring. For example, crossing a carrier female (Xx) with a normal male (XY) shows a 25% chance for each child to be a carrier female, affected male, carrier female, or unaffected male respectively.

Exercise Improvement Advice

It would be beneficial to actually draw the Punnett squares for these scenarios as visual aids. Students can then refer to these visuals to better understand how the genotypes of offspring are derived in X-linked recessive inheritance cases.

Autosomal Inheritance Patterns

While X-linked recessive inheritance deals with genes on the sex chromosomes, autosomal inheritance involves the non-sex chromosomes, or autosomes. Autosomal genes are inherited equally by males and females, which contrasts sharply with X-linked conditions like hemophilia.

In autosomal recessive inheritance, both parents must either be carriers or affected for the child to express the disease. The chance of an offspring being affected if both parents are carriers is typically 25%, with a 50% chance of the offspring being a carrier, and a 25% chance of being completely unaffected.

Comparing autosomal recessive inheritance to X-linked recessive inheritance highlights a key difference: in autosomal, there is no gender preference for the disorder. For hemophilia, if the gene was located on an autosome, we would expect equal ratios of affected individuals among both male and female offspring. This underlines the unique nature of sex-linked genetic disorders and provides a stark contrast to the inheritance patterns observed with genes on autosomes.

Phenotype and Genotype Ratios

Phenotype refers to the observable traits of an organism, such as whether an individual has hemophilia or not. The genotype is the set of genes an organism carries, like 'XX' or 'XY' for a female and male, respectively. In genetics, understanding the relationship between genotype and phenotype is fundamental when predicting trait inheritance.

In our example with hemophilia, using a Punnett square allows us to see the expected phenotype and genotype ratios of offspring. For instance, in Scenario (b), the mating of a carrier female (Xx) with a normal male (XY) results in genotype ratios of 1:1:1:1 for Xx (carrier female), XX (normal female), xY (hemophilic male), and XY (normal male).

Phenotypic ratios can be expressed similarly, showcasing the proportion of affected, carriers, and unaffected individuals in a population. These ratios not only help predict potential outcomes for a single family but also have implications for understanding the spread of genetics traits across larger populations.

Exercise Improvement Advice

Ensuring students grasp the difference between genotype and phenotype is essential for solving genetic problems. Furthermore, emphasizing the methods used to calculate phenotype and genotype ratios, such as using the Punnett square, can improve their comprehension of how these ratios are derived and what they signify in practical terms.