Mitochondrial DNA Disorders Flashcards
What is the respiratory chain, in reference to mitochondria?
A series of 5 membrane-bound protein complexes collectively responsible for oxidative phosphorylation.
Are most mitochondrial genes encoded by nuclear or mitochondrial DNA?
Nuclear.
What is the diameter of mitochondria?
1 micrometer.
What is the size of one mitochondrial chromosome?
16.6 kb
How many DNA molecules are there per mitochondria?
2-10
What percentage of mitochondria DNA is GC?
44%
What nucleotide is the heavy strand of mitochondria rich in?
Guanine
What nucleotide is the light strand of mitochondria rich in?
Cytosine
What is the D loop in mitochondrial DNA?
Small section of triple-stranded DNA due to repeat synthesis of a short segment of the H stand DNA. It is a regulatory region and contain hypervariable regions.
How many genes are the on a mitochondrial chromosome?
37
How many mitochondrial genes specify RNA products?
24
How many mitochondrial genes encode proteins?
13
What percentage of mitochondrial DNA is coding?
93%
What percentage of mitochondrial DNA is non-coding?
7%
What region of mitochondrial DNA is non-coding?
D-loop
Does mitochondrial DN contain introns?
No
Describe the positioning of mitochondrial genes in relation to each other.
Continuous, separated by 1-2 non-coding bases or overlapping.
Explain how the bottleneck effect affects inheritance of mitochondrial genes.
If the mother has heteroplasmy, her primordial germ cells will all contain different mitochondria. As they contain very few mitochondria they will have different numbers of different mitochondria.
What are the four reasons for higher functional mutation rates in mitochondrial compared to nuclear DNA?
93% is coding- higher chance of functional mutation
More rounds of replication- more chance for errors
No histone protection of DNA- oxidative damage (+ mitochondrial function)
Lack of adequate repair mechanisms.
How can heteroplasmy in an individual hinder diagnosis of a mitochondrial disease?
Heteroplasmy may be tissue specific. E.g. analysing blood will not diagnose affected muscle.
Can nuclear DNA cause of modify the mitochondrial genotype?
Yes
What are some symptoms of mitochondrial disease?
Neurological signs, encephalopathy, dementia, ataxia, dystonia, neuropathy, seizures, myopathy, hypotonia, weakness, cardiomyopathy. Also deafness, diabetes, retinal pigmentation, acidosis.
Do all mitochondrial diseases follow an all-or-nothing principle?
No, some are of quantitative measure and appear at a threshold.
What mitochondrial mutations cause leber hereditary optic neuropathy (LHON)?
NADH dehydrogenase subunits 1, 2, 6 (ND1, ND24, ND6) and m11778G-A.
A mutation in what mitochondrial gene causes NARP/ Leigh syndrome?
Subunit 6 of ATPase (m1624C-T).
Give examples of two homoplasmic mitochondrial disorders?
Leber hereditary optic neuropathy (LHON) and NARP/Leigh syndrome.
Give two examples of heteroplasmic mitochondrial diseases.
MELAS and MERFF.
What mitochondrial mutation causes MELAS?
Mutation in leucine in tRNA (m3243A-G).
What mitochondrial mutation causes MERFF?
Mutation in lysine in tRNA (m8344G-A; m8356T-C).
Why does mitochondrial DNA’s high mutation rate benefit forensics and evolutionary studies.
Easy to efficiently assay diversity in many samples.
Polymorphisms are easier to find than in nuclear DNA.
Compare the mutation rate in mitochondrial DNA to nuclear DNA.
50-100 times higher
What regions of mitochondrial DNA are particularly useful for forensic and evolutionary studies?
HV1 and HV2.
What are the advantages of HV1 and HV2?
High variety, small (250-350bp) so easy to amplify using PCR.
How is an individual’s mitochondrial DNA sequence interpreted?
It is compared to the standard reference sequence (Cambridge/Oxford). Relative’s mtDNA can then be compared.
What is a major advantage of mitochondrial DNA over nuclear DNA in forensic and evolutionary studies.
Its high quantity.
