Inheritance Patterns Flashcards
(45 cards)
What are the 3 categories of genetic disorders?
- chromosome abnormalities
- single gene disorders
- multi-factorial & polygenic disorders
What are the 6 common chromosomal abnormalities?
- translocations
- inversions
- deletions
- duplications
- ring chromosome
- fragile site
What is a chromosomal translocation?
- reciprocal: two regions are swapped between two chromosomes.
- robertsonian: 2 acrocentric chromosomes join end to end.
What are chromosomal inversions?
- paracentric: a region of a chromosome is inverted, not involving the centromere.
- pericentric: a region of a chromosome is inverted which includes the centromere.
What are chromosomal deletions?
- interstitial: a region in the middle of the chromosome is deleted.
- terminal: a region at the end of the chromosome is deleted.
What are chromosomal duplications?
- tandem: a region of the chromosome is duplicated so the two identical regions are next to each other.
- inverted: a region of the chromosome is duplicated and inverted.
What are ring chromosomes?
Chromosomes with the ends joined together, forming a ring. Arise when the telomere is deleted.
What is a fragile site in a chromosome? Example of a condition caused by a fragile site?
A region on a chromosome which is prone to replication stress and chromosomal instability.
Fragile X syndrome.
What are the modes of Mendelian inheritance?
- autosomal / sex-linked
- dominant / recessive
What are the non-Mendelian modes of inheritance?
- imprinting
- mitochondrial inheritance
- multifactorial
- mosaicism
What does compound heterozygous mean?
There are two different pathogenic variants of a gene at the same locus.
What is allelic heterogeneity?
When different mutations within the same gene result in the same clinical condition.
What are 3 features of autosomal recessive inheritance?
- males and females affected in equal proportions
- affected individuals only in a single generation
- consanguinity is a risk factor
What is the carrier frequency for cystic fibrosis?
1/25
What is cystic fibrosis?
- most common autosomal recessive condition affecting Northern Europeans
- chronic conditions affecting lungs and gut but can affect other systems
- incidence: 1/2500
Where is the CFTR gene located?
7q31.2
chromosome 7
Does CF have mutational heterogeneity?
Yes, there over 1000 mutations of the CTFR gene leading to CF.
How is someone tested for being a CF carrier?
- standard carrier testing detects the top 29 mutations (90% of all mutations)
- however this is based on white patients so less reliable for BAME patients
How is someone tested for CF?
Sweat test for levels of salt - this is a diagnostic test, not genetic analysis.
How are newborn babies tested for CF?
Neonatal screening program for IRT, an indirect marker of CF (abnormal IRT levels indicate cystic fibrosis)
What is the most common mutation for CF?
ΔF508 - accounts for 80% of CF cases
What are 2 examples of genotype - phenotype correlations in CF?
ΔF508/ΔF508 - correlates with pancreatic insufficiency and chronic lung disease
ΔF508/R117H - correlates with chronic lung disease but most people with this variant combination are pancreatic sufficient.
What is autozygosity?
Homozgyosity by descent - inheritance of the same (pathogenic) variant through two branches of the family.
Often occurs when there is consanguinity over several generations.
How much shared genetic material is there between 1st cousins?
In a consanguineous relationship, what is the risk of autosomal recessive disease in offspring?
Shared genetic material: 1/8
Risk: 1/32
