Question

A girl is a hemophiliac. (a) What are the possible genotypes and phenotypes of her parents? (b) Assuming that her mother is normal, what were this girl's chances of being born with the disease? (c) Several cases of hemophilia in girls have been reported within a small region in England where there is often close intermarriage. Explain this high frequency of hemophilia in girls.

Short answer

(a) The girl's father must be a hemophiliac with genotype \(X^hY\). The mother could either be a carrier with genotype \(X^hX\) or a hemophiliac with genotype \(X^hX^h\). Phenotypically, the father is hemophiliac while the mother could either be normal but a carrier or a hemophiliac. (b) Assuming the girl's mother is normal but a carrier, the probability of the girl being born with hemophilia is 100%. The mother has a 50% chance of passing on the mutant X chromosome, and the father, being a hemophiliac, will always pass on his mutant X chromosome. (c) The high frequency of hemophilia in girls within the small region in England can be explained by the higher probability of inheriting recessive traits like hemophilia due to close intermarriage. Intermarrying carriers of the hemophilia gene increases the likelihood of offspring inheriting two mutant X chromosomes. This increases the number of affected females over generations, thus explaining the high frequency of the disorder in the region.

Step-by-step solution

(Step 1: Understand the Hemophilia Disorder)

Hemophilia is a sex-linked trait, which means that it is carried on the X chromosome. Males have one X and one Y chromosome (XY genotype), while females have two X chromosomes (XX genotype). In the case of hemophilia, males are affected when they inherit a single X chromosome with the hemophilia mutation (X^hY), while females become carriers if they inherit an X chromosome with the mutation and a normal X chromosome (X^hX). When females inherit two X chromosomes with the mutation (X^hX^h), they are affected with hemophilia.

(Step 2: Determine the Parent's Possible Genotypes)

Since the girl is affected with hemophilia (X^hX^h), she must have inherited one mutant X chromosome (X^h) from each of her parents. (a) For the father, since he is male, he only has one X chromosome to contribute. If he contributed the X^h chromosome, he will be affected with hemophilia (X^hY). This is the only possible genotype for the father. (b) For the mother, there are two possibilities as she may be either a carrier (X^hX) or affected with hemophilia (X^hX^h). If she is a carrier, she has a 50% chance of passing the X^h chromosome to her children. If she is affected, she will always pass the X^h chromosome. The possible phenotypes for the mother are normal (but a carrier) or affected with hemophilia.

(Step 3: Calculate the Girl's Chance of Being Born with Hemophilia)

Assuming that her mother is normal (X^hX), there was a 50% chance of the girl inheriting the X^h chromosome from her (since the mother has a 50% chance of passing X^h and a 50% chance of passing X). Since her father has the X^hY genotype, he will always pass the X^h chromosome to his daughters. So, with the mother being normal, the girl had a 100% chance (1 * 1/2 = 1/2) of being born with hemophilia.

(Step 4: Explain the High Hemophilia Frequency in the Small Region)

The high frequency of hemophilia in girls within the small region in England can be attributed to close intermarriage. When family members intermarry, they share a more significant portion of their genetic material, leading to a higher chance of inheriting and expressing recessive traits like hemophilia. When carriers of the hemophilia gene (X^hX or X^hY) intermarry, there is a higher likelihood of their offspring inheriting two mutant X chromosomes (X^hX^h), leading to affected females. Since hemophilia is a sex-linked disorder, the increased probability of passing the hemophilia gene onto offspring increases with each generation of close intermarriage, resulting in the high frequency of the disorder in the region.

Key concepts

Hemophilia Inheritance

Hemophilia is a classic example of an X-linked recessive disorder. Its inheritance pattern is crucial for understanding how the disease is passed on, particularly within families. For a female to be affected by hemophilia, she must receive the defective gene, denoted as X^h, from both of her parents. Thus, her father must have the hemophilia gene (X^hY) and is affected by the disease, as he has no second X chromosome to mask the effect of the recessive gene. Her mother can either be a carrier with one normal X and one hemophilia gene (X^hX) or affected with two hemophilia genes (X^hX^h), which is rarer due to the recessive nature of the trait. This explains why hemophilia is much less common in females, as it requires both parents to contribute the specific allele.

Considering a hemophiliac girl, her father could only pass the X^h chromosome, and her mother must have passed an X^h chromosome as well, whether she is symptomatic or a carrier. This underlines the autosomal recessive inheritance where two copies of the mutated gene are present for the phenotype 'hemophiliac' to be expressed in females.

X-linked Recessive Traits

X-linked recessive traits, such as hemophilia, are determined by genes located on the X chromosome. Because males (XY) have only one X chromosome, a single recessive allele (X^h) will cause the expression of the disease. In contrast, females (XX) have two X chromosomes, and a recessive allele must be present on both for the disease to manifest. Since females have two X chromosomes, they are more likely to be carriers of X-linked recessive disorders without being affected.

This also means that a male cannot pass the trait to his sons (as he provides the Y chromosome), but all of his daughters will be carriers if he is affected, because they will all inherit his single X chromosome with the hemophilia allele. The sex chromosomes carried by the mother and the father directly impact the probability of inheritance of such traits.

Genotypes and Phenotypes

Genotypes refer to the genetic makeup of an individual, whereas phenotypes are the observable characteristics. For an X-linked recessive disease like hemophilia, the genotypes for males are either X^hY (affected) or XY (unaffected), and for females, XX (unaffected), X^hX (carrier), or X^hX^h (affected). The phenotype depends on the genotype: males either have hemophilia or they don't, while females may express the disease if they have two affected X chromosomes or be asymptomatic carriers with one.

Understanding the concept of carriers is particularly important since carriers can still pass on the gene to the next generation without displaying any symptoms themselves, which significantly affects genetic counseling and risk assessments within families carrying the gene for X-linked disorders.

Genetic Probability Calculations

When tackling genetic probability calculations, it is essential to consider the combination of parental genotypes and the Mendelian inheritance patterns. The Punnett square is a tool often used to visualize and calculate the probabilities of offspring genotypes based on the parents' alleles. In the case of hemophilia, a mother who is a carrier (X^hX) has a 50% chance of passing on the hemophilia allele with each pregnancy, and an affected father (X^hY) will always pass the allele to his daughters.

To calculate the probability of a daughter being born with hemophilia from a carrier mother and an affected father: each child has a 50% chance (1 in 2) of inheriting an X^h chromosome from the mother, and since the father can only pass his X^h, the probability is 100% for the daughter to inherit it from him. Consequently, the chance of their daughter having hemophilia is 50% (0.5 multiplied by 1). Such calculations play a fundamental role in genetic counseling, where they help in understanding and predicting the risk of inheriting genetic disorders.