Autosomal dominant inheritance 11/11 & 11/13

Flashcards covering key concepts of autosomal dominant inheritance and associated terminologies related to single-gene diseases.

Mendelian Trait/ Monogenic Trait

A particular genotype at a single locus is the primary determinant of the trait.

Dominant Disorder (trait)

A human monogenic disorder determined by a nuclear gene, manifested in the heterozygote.

A mutation is dominant when heterozygosity for a genetic variant causes a clear pathological phenotype. 

The normal allele on its own is not sufficient to secure normal function.

Aa will be effected

Heterozygote

An individual with two different alleles for a specific gene.

Variable Expressivity

The degree of expression of the phenotype among individuals with the same genotype.

Penetrance

The probability that a person with a particular genotype will express the related phenotype.

I.e. the likelihood that a person carrying a disease-associated genotype will develop the disease.

Ex. A person with achondroplasia allele will develop the disease, 100% penetrate

1. Complete penetrance

2. Reduced penetrance

Reduced Penetrance

An individual carrying a disease-causing genotype might not exhibit the disease phenotype at all, even though he or she can transmit the disease-causing mutation to the next generation.

Obligate carrier: an individual who has an affected parent and affected children and therefore he/she must be a carrier of the mutation.

Achondroplasia

An autosomal dominant disorder characterized by skeletal dysplasia.

Marfan Syndrome

An autosomal dominant multisystem disorder caused by mutations in the FBN1 gene.

Neurofibromatosis

An autosomal dominant disorder characterized by growth of multiple benign tumors in different parts of the body.

Huntington Disease

An autosomal dominant neurological disorder caused by mutations in the HD gene, characterized by progressive movement disturbances.

Tri-nucleotide Repeat Expansion

An abnormal long expansion of trinucleotides that can cause certain genetic disorders, including Huntington disease.

Anticipation

The phenomenon where signs and symptoms of genetic disorders become more severe and appear at earlier ages as the disorder is passed through generations.

Autosomal Dominant Inheritance

Dominant traits have a distinctive pattern of inheritance

1. Every affected individual should have at least one affected parent. Successive generations are affected.

2. Males and females are affected equally, autosomal trait

3. The phenotype in homozygous dominant individuals (AA) is often more severe than the heterozygous phenotype (Aa).

Autosomal Dominant and Recurrence risk

The likelihood of an offspring inheriting an autosomal dominant trait from an affected parent. Each child has a 50% chance of being affected if one parent carries the dominant allele.

Clinical examples of autosomal dominant disorders and factors affecting pedigree patterns

1. Achondroplasia

2. Marfan syndrome

3. Neurofibromatosis Type 1 and type 2

4. Huntington disease