Exercises: Pedigree analysis

Explain the meaning of the basic symbols of a pedigree: squares and circles, filled and empty symbols, the horizontal line joining two individuals and the vertical line descending from it.

Describe two features of a pedigree that make you suspect that a disease is inherited with an autosomal dominant pattern, and justify each of them.

Describe two features of a pedigree that make you suspect that a disease is inherited with an autosomal recessive pattern, and explain why healthy parents with affected children are often found in these pedigrees.

A couple in which both members suffer from the same hereditary disease have three children: two affected and one healthy. Reason whether the disease can be due to a recessive allele or to a dominant one and state the most probable genotype of the parents.

Two healthy parents have a daughter affected by a hereditary disease. Reason why the disease must be due to a recessive allele and why, in addition, it cannot be inheritance linked to the X chromosome.

What minimum information must a pedigree contain in order to be able to deduce the pattern of inheritance of a trait? State at least three essential pieces of data and justify their usefulness.

The pedigree in the diagram shows the transmission of a hereditary disease over three generations; the filled symbols correspond to affected individuals. a) Deduce the most probable pattern of inheritance of the disease and justify it. b) State the genotype of individuals I-1 and I-2. c) State the possible genotypes of the individual marked with ? and the probability that she is a carrier, reasoning your answer.

In a family, the same disease appears in the grandfather, in a daughter of his and in two of her three children, affecting men and women equally; on the other hand, no child of the healthy people in the family is affected. Deduce the most probable pattern of inheritance and assign the most probable genotypes to the three generations.

Phenylketonuria is an autosomal recessive disease. A couple of first cousins, both healthy but with a family history of the disease, have an affected child. a) State the genotypes of the parents. b) Calculate the probability that their next child will also suffer from the disease. c) Explain why consanguinity increases the probability of recessive diseases appearing in the offspring.

For an autosomal recessive disease, a healthy woman has an affected brother; her parents are both healthy. The woman marries a healthy man whose father was affected and whose mother was homozygous normal. a) Calculate the probability that the woman is a carrier. b) State the husband's genotype. c) Calculate the probability that the couple's first child will suffer from the disease.

Huntington's disease is due to an autosomal dominant allele of late onset, which usually appears from the age of 40-50. The father of a 30-year-old woman, currently healthy, developed the disease at 50. a) State the probability that the woman has inherited the allele. b) Calculate the probability that a child of hers will inherit it. c) Explain why late-onset dominant diseases pose a special problem in pedigree analysis and in genetic counselling.

For an autosomal recessive disease, the frequency of healthy carriers in the general population is 1 in 25. A healthy man has an affected sister, and he is considering having children with a woman with no family history of the disease. a) Calculate the probability that the man is a carrier. b) Calculate the probability that the couple will have an affected child. c) Reason how the risk would change if the couple were first cousins with a common affected grandfather, without doing the numerical calculation.

Unit challenge. Imagine you work in a genetic counseling unit and must prepare a technical report on the transmission of traits in your own family environment.

1. Data collection: Survey at least $5$ relatives regarding three traits: attached or free earlobes (simple Mendelian inheritance), ABO blood group (multiple alleles and codominance), and color discrimination using an online Ishihara test (sex-linked). If you do not know a blood group, record it as unknown (population frequencies cannot assign the blood group of a specific person).

2. Pedigree construction: Design the standardized family pedigree using international symbols. Deduce and assign the most probable genotypes to each individual for the three analyzed traits.

3. Calculation of genetic risks: Using Punnett squares, calculate the phenotypic probabilities for your hypothetical offspring if your partner were heterozygous for earlobes, had blood group $AB$ ($I^A I^B$), and were a carrier of color blindness ($X^D X^d$). Express probabilities as a percentage or decimal value (for example, $0.25$).

Submit your report with the pedigree, the worked-out crosses, and a brief conclusion on the reproductive prognosis.

Evaluation criteria:

• Technical rigor in pedigree symbolism and logical deduction of family genotypes.

• Correctness in setting up the crosses and in the mathematical calculation of probabilities.

• Precise conceptual differentiation between Mendelian, codominant, and sex-linked inheritance.