Genetics 2 Flashcards
What are the 3 non mendelian patterns of inheritance?
- anticipation (nucleotide repeat disorders)
- mitochondrial
- multifactorial
What is anticipation? what is it due to? how many disease follow this pattern? when does the repeat occur more often in fathers? mothers?
- some genetic diseases have an earlier age of onset, or increased severity in more recent generations
- due to dynamic mutations- expansion of trinucleotide repeats
- more than 20 diseases follow this pattern
- when repeats is in an exon, expansion occurs is father
- when in UTR, expansion occurs in mother
What is huntingtons disease? penetrance? symptoms? treatment?
- anticipation pattern
- autosomal dominant disorder
- penetrance near 100%
- progressive neurodegeneration causing slowly progressive movement disorder with intellectual impairment and psychiatric disturbance, dementia
- no treatment or cure
Cause of huntingtons disease? what do longer repeats correlate with? function of protein?
exonic polyglutamine expansion in huntington protein:
- e 40 repeats fully penetrant
- longer repeats correlate with earlier onset
- normal function of this protein is unclear
- expanded proteins forms inappropriate aggregates with other proteins (gain of function)
What is myotonic dystrophy? symptoms?
- most common muscular dystrophy in adults
- autosomal dominant
- progressive muscle deterioration
- myotonia
- cardiac arrhythmia
- testicular atrophy
- insulin resistance
- cataracts
Causes of myotonic dystrophy? severity? age of onset? repeat number?
Expansion of 3’ UTR of affected gene (RNA gain of function)
-severity increases and age of onset decreases through generations
- repeat number correlates with severity:
- 5-37 = unaffected
- 50-100 = mild
- 100-1000s= full disease
-large repeats transmitted almost exclusively by females
Who is mitochondria inherited from? why?
- mother
- b/c mitochondria are located in the cytosol
- affects males and females equally
heteroplasmy in mitochondria?
- b/c each cell has a population of mtDNA molecules, a single cell will have some that carry a mutation and some that do not
- this causes a great deal of variability in expression of mitochondrial diseases
- mutation severity varies too
which tissues are affected more severely by mitochondrial diseases?
tissue with higher ATP requirements are most often and severely affected
-CNS consumes 20% of ATP produced in body
Which has a higher mutation rate: mtDNA or nuclear DNA?
mitochondrial
What is Leber hereditary optic neuropathy (LHON)? symptoms? when does it begin?
- mitochondrial disease
- rapid loss of vision in central field due to death of optic nerve
- begins in 3rd decade of life
- usually irreversible
- heteroplasmy minimal, expression relatively uniform in affected families
What is MELAS? when does it present? symptoms?
- mitochondrial encephalopathy, lactic acidosis, stroke like episodes
- mitochondrial inheritance
- may present at any time in life
- progressive neurological deterioration and seizures
- wide range of expression, even in same family
What is kearns sayre syndrome (KSS)? symptoms?
- mitochondrial
- muscle weakness, cerebellar damage, heart failure
What is MERRF?
- myoclonic epilepsy, ragged red fibers in muscle, ataxia, sensorineural deafness
- mitochondrial
What is retinas pigments? genes? symptoms? cause?
- mitochondrial
- most common inherited cause of blindness
- locus heterogeneity (45 different genes)- results in different patterns of inheritance in different families, some cases due to mt mutations
- begins with night blindness and progresses to daytime vision
- most are legally blind by age 40
- pigments deposited on retinal surface as pathological changes accumulate
