Autosomal dominant and recessive inheritance

Question 1

What are some characteristics of autosomal dominant inheritance? ( AD )

Answer 1

Autosomal dominant inheritance is characterized by vertical transmission of the disease phenotype, a lack of skipped generations, and roughly equal numbers of affected males and females. Father-to-son transmission may be observed. Example: Postaxial polydactyly ( extra finger/toe )

Question 2

What is recurrence risk?

Answer 2

The chance of a parent’s future child/children being affected by a genetic disease.

Question 3

What are some characteristics of autosomal recessive inheritance? ( AR )

Answer 3

Autosomal recessive inheritance is characterized by clustering of the disease phenotype among siblings, but the disease is not usually seen among parents or other ancestors. Equal numbers of affected males and females are usually seen, and consanguinity may be present.

Question 4

Are the clinical effects different between AD or AR diseases?

Answer 4

Although the distinction between dominant and recessive diseases is not rigid, a dominant disease allele will typically produce disease in a heterozygote, whereas a recessive disease allele will not.

Question 5

The same disease, different modes of inheritance

Answer 5

In some cases a disease may be inherited in either autosomal dominant or autosomal recessive fashion, depending on the nature of the mutation that alters the gene product.
Familial isolated growth hormone deficiency (IGHD)
β-thalassemia

Question 6

What is a de novo mutation? What are some characteristics?

Answer 6

The gene transmitted by one of the parents underwent a de novo ( new ) mutation. De novo mutations are a common cause of the appearance of a genetic disease in a person with no previous family history of the disorder. The recurrence risk for the person’s siblings is very low, but the recurrence risk for the person’s offspring may be substantially increased.

Question 7

What is the germline?

Answer 7

The germline is the population of a multicellular organism’s cells that pass on their genetic material to the progeny. In other words, they are the cells that form the egg, sperm and the fertilised egg.

Question 8

What are some characteristics of germline mosaicism?

Answer 8

Germline mosaicism occurs when all or part of a parent’s germline is affected by a disease-causing mutation but the somatic cells are not ( the parent is not affected ). It elevates the recurrence risk for offspring of the mosaic parent.

Question 9

What is reduced penetrance?

Answer 9

Reduced penetrance describes the situation in which persons who have a disease-causing genotype do not develop the disease phenotype.

Question 10

Define age-dependent penetrance.

Answer 10

A delay of the onset of a genetic disease ( Example: Huntington’s disease, around 30 years of age ). This complicates interpretation of inheritance patterns in a family. Natural selection against the disease causing allele is reduced, increasing the frequency in the population.

Question 11

Define variable expression.

Answer 11

The degree of severity of the disease phenotype.

Question 12

What can influence the severity of disease expression?

Answer 12

Environmental factors ( diet, exercise, exposure to harmful agents like tobacco ), Interactions of modifier genes with the disease-causing gene, or different alleles at the same disease locus on the gene ( allelic heterogeneity )

Question 13

Define locus heterogeneity.

Answer 13

A single disease phenotype can be caused by mutations at different loci in different families, which is termed locus heterogeneity.

Question 14

What makes a gene pleiotropic?

Answer 14

Genes that exert effects on multiple aspects of physiology or anatomy are pleiotropic. Pleiotropy is a common feature of human genes.

Question 15

Define consanguinity.

Answer 15

Mating of people who are related.

Question 16

What are the consequences of consanguinity?

Answer 16

1. Consanguinity increases the chance that a mating couple will both carry the same disease-causing mutation. It is seen more often in pedigrees involving rare recessive diseases than in those involving common recessive diseases.
2. At the population level, consanguinity increases the frequency of genetic disease and mortality. The closer the degree of consanguinity, the greater the increase.