Mitochondrial Genetics Flashcards
Definitions of homoplasmy
All copies of mitochondrial DNA in mitochondria are identical
Definition of heteroplasmy
More than 1 type of mitochondrial DNA present in mitochondria
What are the main 5 functions of the mitochondria
Cellular energy production Apoptotic cell death Intracellular signalling Lipid metabolism Thermogenesis
Describe the genetic composition of mitochondrial DNA
Circular DNA
Codes for protein of OXPHOS
- 13 polypeptides
- 22 tRNA
- 2 rRNA
Each mitochondria contains many copies
-brain and heart have the most
What are the 2 types of mitochondrial DNA
Homoplasmy
- all copies in mitochondria are identical
- any variants present in the same loci
Heteroplasmy
- more than 1 type of MT genome present
- any variants present in different loci => variation
Between the nuclear and mitochondrial genome, compare the
- relative size
- no of DNA molecules/cell
- no of genes encoded
- introns, histones
- mode of inheritance
- transcription method
Relative size
- 3.3x10^9 bp
- 16600 bp
no of DNA molecules/cell
- 23 in haploid, 46 in diploid
- several 1000 copies/cell
no of genes encoded
- 20000-30000
- 37
introns and histones
- yes
- no
mode of inheritance
- mendelian
- matrillineal
transcription method
- individual transcription
- polycistronic
Describe the relationship between the nuclear DNA and mitochondria
Proteins encoded in the nuclear genome needed for mitochondrial function
- Oxphos chain
- replication, transcription, processing and repair of mtDNA
BASICALLY ESSENTIAL FOR CELLULAR ENERGY PROD
Describe the main characteristics of mitochondrial disorders
- Respiratory chain deficiency
- Decreased cellular O2 consumption, ATP synthesis
- Increased lactic acid in blood and cerebral fluid
- Sometimes ATP prod unaffected but increased production of reactive O2
- May manifest in many systems and tissues
- More likely to influence tissues with increased energy demands
What are the 3 origins of mitochondrial disease
Nuclear origin
Nuclear origin with mitochondrial dysfunction
Mitochondrial origin
Describe how mitochondrial disease can be caused by nuclear genome mutations
What is an example of mitochondrial disease caused by nuclear genome
Same inheritance pattern as Mendelian disorders
Caused by defects to genes involved in replication, transcription, translation, MT DNA repair
Friedreich Ataxia
-autosomal recessive neurodegenerative disorder
Describe how mitochondrial disease can be caused by nuclear genome mutations with mitochondria dysfunction dependence
What is an example
Defects in genes that monitor/regulate mitochondria
Needs mitochondria dysfunction
More common as you age
Parkinsons disease
How does Parkinson’s disease work and affect mitochondrial function
2 genes involved
-PINK1, Parkin
- Normally PINK imported into MT => cleaved and released
- Damage to MT => membrane depolarisation => PINK accumulates in outer MT membrane
- Parkin recruited to mitochondria and triggers autophagy
Damage to this pathway => build up of defecting MT
Describe how mitochondrial disorders caused by mutations in the mitochondrial genome arise
Which part of the MT genome is affected most often
What is an example
Caused by point mutations/rearrangements
Similar general features to disorders caused by nuclear mutations
Matrillineal, high % in tRNA
Leber’s hereditary optic neuropathy (LHON)
- most common disease, mainly in men
- homoplasmic mutation in 1 of 3 genes
Describe the threshold model
What are the 3 outcomes
Mutations causing disease may be heteroplasmic with a threshold
Low level
-no effect
Med level
- mild symptoms
- late acting, non fatal but debilitating
High level
- more severe symptoms
- can be fatal
How does the threshold model vary depending on the body part affected
What are the risks of this
Mutant loads in each part of the body can vary
Can have a high mutant load in 1 body part but if below threshold, no expression in phenotype
Easily passed on unknowingly, v high prevalence of mutant MT
