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.

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.

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.

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.

State two features of a pedigree that point towards recessive inheritance linked to the X chromosome, and explain why most of those affected in this pattern are male.

In a recessive disease linked to the X chromosome, an affected man has sons and daughters with a healthy non-carrier woman. Explain to which of his descendants he will certainly transmit his X chromosome with the mutant allele and what consequence this will have on the appearance of the pedigree.

A woman with normal vision whose father was colour-blind is married to a man with normal vision. The couple have four children: a healthy daughter, a carrier daughter, a healthy son and a colour-blind son. a) Assign genotypes to the parents and to each of the children. b) Explain which feature of this family is characteristic of inheritance linked to the X chromosome.

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.

A healthy couple have four children: two healthy boys, one boy affected by a hereditary disease and one healthy girl. Years later, the healthy daughter has, with a healthy man, a son affected by the same disease. a) Reason whether the disease fits an autosomal recessive pattern or a recessive X-linked one better. b) Assign the genotypes of the first couple and of the daughter. c) State what a priori probability the daughter had of being a carrier.

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.

A couple attend a genetic counselling appointment. The man's paternal grandfather suffered from an autosomal dominant disease with complete penetrance, but the man's father, aged 60, is healthy. On the woman's side, her mother is a known carrier of a recessive disease linked to the X chromosome. a) State, with reasoning, what probability the man has of transmitting the dominant disease. b) Calculate the probability that the woman is a carrier of the X-linked disease. c) Calculate the probability that the couple's first son will suffer from that disease. d) Summarise what genetic counselling consists of and what decisions it can help to make.