Genetics Flashcards
Inheritance of Leders Hereditary Optic Neuropathy
Mitochondrial with Heteroplasmy so variable expression and arises later in life
(Individuals do not experience vision difficulties until adulthood because only some mitochondria have mutant copies of gene
Causes bilateral, painless subacute loss of central vision during young adult life)
Gonadal/Germiline mosaicism
where an individuals germline cells develop mutation during embryonic growth but the somatic cells do not this results in the individuals offspring being affected, but not themselves.
Parent will not have mutated somatic cells on testing, but offspring will.
Linkage Disequilibrium
Linkage disequilibrium is the non-random association of alleles at two or more loci, not necessarily on the same chromosome. There is associations in populations of alleles more than what would be expected if they were unlinked.
Disorders with Trinucleotide repeats
Huntingtons - CAG repeats
Frederich Ataxia - GAA repeats
Myotonic dystrophy - Autosomal dominant with CTG repeats
Fragile X - X linked with CGG repeats
Mutations in variants of Muscular Dystrophy
All X-linked recessive
- Duchenne MD - frame-shift mutation (worst)
- Beckers MD - In-frame mutation
- MD Cardiomyopathy - Promoter region mutation (best)
Examples of diseases with Frame-shift mutations
- CCR5 receptor in HIV
- Duchennes MD
- Tay-Sachs disease (usually causes death as toddler_
What pattern in a pedigree makes autosomal dominant likely?
Father to Son transmission
Types of point mutations/single nucleotide variants
Frame-shift due to insertion or deletion that are not multiples of 3
Nonsense results in unwanted stop codon
Missence results in single different amino acid
Splice mutations occur at site of intron and exon splicing which can cause loss of exon or inclusion of intron altering the protein code
Imprinting disorders
Has phenotypic effect if Pt has inherited 2 copies of genes from one parent and none from other, then the copies are imprinted
- Prader Willi Syndrome
- Angelmans syndrome
- Beckwith Weidman Syndrome
- Russel Silver Syndrome
- Transient neonatal hypoglycaemia
- matUPD14
- patUPD14
- Pseudohypoparathyroidism
X-linked dominant disorder
Rett syndrome - primary females affected, growth and IQ disabilities
Autosomal dominant disorders
Cardiac congenital disorder except Fabrys;
- Brugada
- Long QT syndrome
- Arrythmogenic RV cardiomyopathy
- HCM
- Marfans
- Loey Dietz
- Myotonic dystrophy
- Familial Adenomatous Polyposis
- Huntingtons disease
- Neurofibromatosis Type 1
- Familial Hypercholestraemia
Trinucleotide disorders
- Huntingtons, autosomal dominant (> 40 CAG repeats)
- Fredreichs Ataxia, autosomal recessive (CGG repeats)
- Myotonic Dystrophy, autosomal dominant (CTG repeats)
- Fragile X , X-linked (mixed recessive and dominant - CGG repeats)
- Spinocerebellar Ataxia, autosomal dominant
Mitochondrial disorders
Heterozomy - Leber Optic atrophy with blindness in older age
Homozomy - MELAS, Myoclonic epilepsy with ragged red fibres
Uniparental Disomy
2 x chromosomes from ONE parent. Only causes an issue if imprinted chromosomes
i.e. Prader Willi, Angelmans
Linkage Disequilibrium
A correlation between nearby alleles at neighboring polymorphs are associated within a population more often than if they were unlinked.