In humans, hemophilia A (OMIM 306700) is an X-linked recessive disorder that affects the gene for factor VIII protein, which is essential for blood clotting. The dominant and recessive alleles for the factor VIII gene are represented by H and h. Albinism is an autosomal recessive condition that results from mutation of the gene producing tyrosinase, an enzyme in the melanin synthesis pathway. A and a represent the tyrosinase alleles. A healthy woman named Clara (II-2), whose father (I-1) has hemophilia and whose brother (II-1) has albinism, is married to a healthy man named Charles (II-3), whose parents are healthy. Charles's brother (II-5) has hemophilia, and his sister (II-4) has albinism. The pedigree is shown below.

What are the genotypes of the four parents (I-1 to I-4) in this pedigree?

Verified step by step guidance

1. Step 1: Understand the inheritance patterns. Hemophilia A is X-linked recessive, meaning males (XY) with the recessive allele (h) will express the disorder, while females (XX) must have two recessive alleles (hh) to express it. Albinism is autosomal recessive, meaning individuals must inherit two recessive alleles (aa) to express the condition.
2. Step 2: Analyze the pedigree for hemophilia. Clara's father (I-1) has hemophilia, so his genotype must be XʰY. Clara (II-2) is healthy but her father passed on his Xʰ chromosome, so her genotype must be XʰX. Charles's brother (II-5) has hemophilia, so their mother (I-3) must be a carrier (XʰX) and their father (I-4) must be XʜY.
3. Step 3: Analyze the pedigree for albinism. Clara's brother (II-1) has albinism, so both parents (I-1 and I-2) must carry the recessive allele (Aa). Charles's sister (II-4) has albinism, so both parents (I-3 and I-4) must also carry the recessive allele (Aa).
4. Step 4: Combine the information for Clara's parents. Clara's father (I-1) is XʰY and Aa (carrier for albinism). Clara's mother (I-2) is XʜX and Aa (carrier for albinism).
5. Step 5: Combine the information for Charles's parents. Charles's father (I-4) is XʜY and Aa (carrier for albinism). Charles's mother (I-3) is XʰX and Aa (carrier for albinism).

Key Concepts

X-linked Recessive Inheritance

X-linked recessive inheritance refers to traits that are associated with genes located on the X chromosome. In this pattern, males (XY) are more likely to express the trait because they have only one X chromosome, while females (XX) can be carriers if they have one affected X and one normal X. Hemophilia A is a classic example, where affected males inherit the disorder from carrier mothers.

Autosomal Recessive Inheritance

Autosomal recessive inheritance involves genes located on non-sex chromosomes (autosomes). For an individual to express a recessive trait, they must inherit two copies of the recessive allele, one from each parent. Albinism, caused by mutations in the tyrosinase gene, exemplifies this inheritance pattern, where both parents must carry at least one recessive allele for their child to be affected.

Pedigree Analysis

Pedigree analysis is a diagrammatic method used to trace the inheritance of traits through generations in a family. It helps identify the genotypes of individuals based on their phenotypes and the phenotypes of their relatives. By analyzing the pedigree provided in the question, one can deduce the genotypes of the parents based on the inheritance patterns of hemophilia and albinism in their offspring.