W6-Lecture 4.1 - Principles of Mendelian Inheritance - part 2 Flashcards
Characteristics of Autosomal dominant inheritance
- Successive generations affected (disease passed down from 1 generation to the next)
- Males and females equally affected
- Both males and females are able to transmit
- Male to male (father to son) transmission observed
Features of Autosomal Dominant inheritance
- Penetrance:
*Percentage of individuals expressing the disorder to any degree
*When frequency of expression is <100% = incomplete/reduced penetrance
*Some show age-dependent penetrance - Variable expressivity:
*Variation in the severity of the disorder in individuals who have the same disease allele
*Interfamilial vs intrafamilial variable expression - Anticipation:
*Worsening of the disease severity with successive generations
*Occur in triplet repeat disorders (Principles of Genetic Inheritance Part II) - Pleiotropy:
Manifestation of the AD disease in different body systems in numerous ways - New mutation rate:
*Varies between AD disorders
*The sudden unexpected appearance of an AD condition arising as a result of a mutation
occurring in the transmission of the gene
*Paternal age effect - Somatic mosaicism
*New mutation arises early in embryogenesis - Gonadal mosaicism:
-A new mutation arising during oogenesis or spermatogenesis
*Implications of recurrence risk counselling - Allelic heterogeneity
-Phenomenon in which different mutations at the same locus result in the same disorder
Characteristics of neurofibromatosis type 1
neurofibromatosis type 1 is an autosomal dorminant disoder, resulting from a mutation on a tumour supressor gene (NF1) on chromosome 17.
It characteristics involve:
- café au lait macules;
- axillary and inguinal freckling;
- neurofibromas;
-and iris Lisch nodules
Neurofibromatosis type 1 (NF1) principles contributing to inheritance pattern observed in neurofibromatosis type 1.
- Autosomal dominant inheritance
- Variable expressivity
- Complete penetrance
- New mutations in 50%
- Allelic heterogeneity
- Pleiotropy
Autosomal Recessive inheritance
Two mutant alleles required to
manifest the trait/disorder
*both parents are carriers of mutated gene, in most cases
Autosomal Recessive inheritance
Two mutant alleles required
to manifest the trait/disorder
Characteristics of Autosomal dominant inheritance
- Disease present in every generation
- Males and females equally affected
- Both males and females are able to transmit
- Parents may be related (consanguineous
In which circumstances are we more likely to see offsprings presenting with Autosomal Recessive disoders?
In offsprings born to carrier parents. Both parents are carriers of the disease.
What determines whether the population will see more of the autosomal recessive disoder or not?
- The frequency of carriers in the population.
*Precise risk for general population depends on the frequency of carriers in the population
What increases the risk of Autosomal recessive disoder?
Risk of AR disorder increases if it is a common condition, or there is consanguinity
Name the common conditions of Autosomal recessive inheritence
- Cystic fibrosis,
- spinal muscular atrophy,
- oculocutaneous albinism,
- most inborn errors of metabolism (e.g. galactosemia)
Features of Autosomal Recessive Inheritence
- Locus heterogeneity:
-Phenomenon whereby mutations at different loci (i.e. in different genes) result in the
same or similar clinical phenotype/condition
-examples of conditions with locus heterogeneity include: oculocutaneous albinism, Fanconi anaemia, galactosaemia - Allelic heterogeneity
*Phenomenon whereby different types of mutations at the same locus (i.e. in the same
gene) result in the same or similar clinical phenotype/condition - Compound heterozygotes:
*The presence of two (or more) different mutations at the same locus, constituting allelic (or mutational) heterogeneity - Double heterozygotes:
The presence of two different mutated alleles at two separate loci
-Example of conditions with double heterozygotes: Sensorineural hearing impairment
