Pedigree analysis
Ireland has one of the highest rates of cystic fibrosis in the world, and every baby born here has a heel-prick screening test in the first days of life. When a family learns that a child is affected, the first thing a genetic counsellor does is draw a pedigree (family tree). A pedigree summarises in a diagram how a trait has been passed on in a family over several generations. Knowing how to read one — and, above all, how to deduce the most likely pattern of inheritance from it — is one of the most direct applications of Mendel's Laws of Segregation and Independent Assortment to real cases, and the basis of genetic counselling.
Symbols and reading a pedigree
To be useful, a pedigree must show at least: the sex of every individual (square or circle), who is affected and who is not (filled or empty), how individuals are related (couple lines and lines of descent, including siblings) and the generation numbers (I, II, III). Without the relationships you cannot see who passed the trait to whom, and without the unaffected individuals you cannot spot skipped generations or the ratio of affected children.
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…
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…
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…
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.
Autosomal dominant versus recessive patterns
In a clinic at a Dublin hospital, two family trees are reviewed: in family A, a form of polydactyly appears in grandparents, parents and children without a break; in family B, two parents with normal pigmentation unexpectedly have a child with albinism. Which mechanisms of transmission explain why some traits never miss a generation while others reappear after staying hidden?
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 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…
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…
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…
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.
X-linked recessive pattern
Calculating probabilities and genetic risk
A healthy couple who already have a daughter with cystic fibrosis go to genetic counselling because their second child, a son, has been born completely healthy. Their healthy son has a sister with the disease: why is the chance that he is a carrier $2/3$ and not $1/2$ or $1/4$?
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…
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…
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.
Complex cases and genetic counselling
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…
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…
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.
X-linked dominant inheritance: justifying a pedigree
In a model of complete X-linked dominance, with complete penetrance and no new mutations, one $X^D$ allele is enough to express the trait. An affected father passes his X to all his daughters and his Y to all his sons: there is no direct transmission from father to son.
Summary
Back to the start: a counsellor reading a family's pedigree decides whether the pattern is dominant, recessive or X-linked, and then uses probability to give the family an exact risk.