Lecture 19-Mitochondrial genetics Flashcards
What is the difference between mDNA and nDNA? (4)
- mDNA is much more gene dense than nDNA
- mDNA doesn’t have introns
- mDNA has a higher spontaneous mutation rate
- mDNA doesn’t replicate with the cell cycle
What’s the size of mDNA?
- 16.5kb
How many genes does mDNA have? What do they code for?
- 37: 22 tRNAs, 2 rRNAs, 13 subunits of the ETC
The vast majority of mitochondrial proteins are encoded in the ______
nucleus
Heteroplasmy
- having both normal and abnormal mit in a cell or tissue and can vary from tissue to tissue
What is the bottleneck effect?
- the random distribution of affected and unaffected mitochondria from a heteroplasmic mothers egg into new eggs. The proportion of affected mitochondria into a given egg determines severity of disease in the child
mitochondrial diseases are clinically heterogeneous in that they ______
can show up in any person at any age, in any tissue in any place.
Note: mitochondrial diseases have extreme clinical variability!
.
Mitochondrial dysfunction can be primary in that it affects a critical mitochondrial protein (or the mDNA or nDNA) or secondary to _______.
- infections (herpes)
- medications
- physiologic stressors (starvation)
Mitochondrial diseases primarily affect what tissues?
- those that are metabolically active like: the heart, brian, liver, muscle
Why may mitochondrial diseases be provoked by illness or starvation?
When we’re sick our defective mitochondria may not be able to meet our bodies’ needs if they’re diseased. Often, people with these diseases are asymptomatic until they get some sort of infection/sick
Mitochondrial cytopathies: CNS (7)
- myoclonus
- generalized seizures
- stroke
- migraine headache
- ataxia
- mental retardation
- psychiatric disease
Mitochondrial cytopathies: Skeletal muscle (4)
- myopathy (hypotonia)
- CPEO (progressive paralysis of the eye muscle)
- recurrent myogloburia
- weakness/fatigue
Mitochondrial cytopathies: bone marrow (2)
- anemia
- pancytopenia
Mitochondrial cytopathies: renal function (1)
- fanconi syndrome (spilling of aas into urine)
Mitochondrial cytopathies: systemic symptoms (4)
- lactic acidosis
- short stature
- fatigue
- failure to gain weight
Mitochondrial cytopathies: endocrine (4)
- DM (islet cells are very metabolically active)
- hypoparathyroidism
- exocrine pancreatic failure
- thyroid disease
Mitochondrial cytopathies: heart (2)
- cardiomyopathy
- conduction defects
Mitochondrial cytopathies: vision (2)
- optic neuropathy
- retinitis pigmentosa
Mitochondrial cytopathies: hearing (2)
- high frequency hearing loss
- aminoglycoside-induced deafness
Mitochondrial cytopathies: gi (3)
- pseudo-obstruction (failure of peristalsis)
- constipation
- vomiting
Mitochondrial cytopathies: liver (3)
- hypoglycemia
- gluconeogenic defects
- liver failure and cirrhosis