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.

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.

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.

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.

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.

In the pedigree of a family it is observed that a disease is transmitted by all affected women to all their sons and daughters, while no affected man transmits it to any of his descendants. Deduce what type of inheritance this disease shows and justify it from where its genetic information is located and how it is transmitted.

Three different pedigrees are studied. In pedigree A, all the children of affected women have the disease and no child of affected men has it. In pedigree B, the disease appears in every generation and affects men and women equally, and every affected person has at least one affected parent. In pedigree C, the disease skips generations, almost always affects males and is never transmitted from father to son. a) Assign to each pedigree the most probable pattern of inheritance. b) Justify each assignment from the features described. c) State in which of the three cases women can be healthy transmitters of the disease.

In a family there are two independent traits: hereditary deafness, autosomal recessive, and colour blindness, recessive and linked to the X chromosome. A healthy, non-colour-blind man, whose father was deaf, has children with a healthy woman who is a carrier of the colour blindness allele and whose mother was deaf. a) State the genotypes of the couple. b) Calculate the probability that they will have a deaf, colour-blind son. c) Calculate the probability that they will have a daughter who is healthy for both traits. d) Reason whether any daughter of this couple could be colour-blind.

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.

Explain which feature of a pedigree makes it possible to distinguish a dominant disease linked to the X chromosome from an autosomal dominant one, taking as a reference what happens to the sons and daughters of affected men in each case.

The medical history of a blood clotting abnormality is investigated in a three-generation family:

• In generation I, an affected male (I-1) and a healthy woman with no family history (I-2) have two offspring: a healthy daughter (II-2) and a healthy son (II-3).

• Female II-2 has offspring with a healthy man (II-1): their first son (III-1) has the abnormality, their second son (III-2) is healthy, and their third child (III-3) is a healthy daughter.

• Male II-3 has two healthy daughters with a healthy woman with no family history.

1. a) Draw the complete pedigree using international standard symbols and indicate the most likely genotype of each individual.
2. b) Argue in detail why the transmission pattern corresponds to X-linked recessive inheritance, justifying why it cannot be Y-linked inheritance nor autosomal dominant inheritance.
3. c) Explain the concept of "criss-cross inheritance" applying it to this pedigree, pointing out the specific transmission path of the mutated allele from generation I to individual III-1.
4. d) If woman III-3 has offspring with a healthy male, calculate the probability that their first child (whether male or female) will manifest the disease and the probability that they will have a carrier daughter.

Vitamin D-resistant hypophosphataemic rickets is a dominant disease linked to the X chromosome. An affected man and a healthy woman have three daughters and two sons: all the daughters are affected and no son is. a) Explain why this result is the one expected for this pattern of inheritance. b) Assign the genotypes of the parents and of the children. c) If one of the affected daughters has children with a healthy man, state what proportion of her sons and daughters would be expected to be affected, justifying your answer.

In the pedigree of a rare disease the following is observed: in generation I, an affected man and a healthy woman have, in generation II, an affected daughter and a healthy son; the affected daughter has, with a healthy man, in generation III, an affected son and a healthy daughter. a) Reason whether the pedigree is compatible with autosomal dominant inheritance. b) Reason whether it is compatible with dominant inheritance linked to the X chromosome. c) Reason whether it is compatible with autosomal recessive inheritance. d) Conclude which pattern or patterns are the most parsimonious for a rare disease and justify your answer.