Mitochondrial genetics Flashcards
(30 cards)
What are the two types of nontraditional patterns of inheritance we’ve discussed?
Mitochondrial inheritance and uniparental disomy
Mutations affecting mitochondria alter what mitochondrial function?
ATP production
Mitochondrial porins allow tansit of molecules of what size?
<5000 Da
True or false: many of the proteins that function in the mitochondria are encoded for by mitochondrial DNA, are made in the matrix of the mitochondria, and are transported to the cytoplasm.
False: many of the proteins that function in the mitochondria are encoded for by nuclear DNA, are made in the cytoplasm, and transported to the mitochondria.
What portion of the circular mtDNA is coding region?
80%
True or false: mtDNA uses different codons than nuclear DNA.
True
AGA and AGG are also stop codons
Why are the mitochondria in sperm not transmitted to the fertilized egg?
The mitochondria in sperm are ubiquinated for destruction.
Although mitochondrial traits will be transmitted from a mother to all her children, why may some of the traits not be expressed phenotypically?
Incomplete penetrance and variable expressivity.
What is replicative segregation?
Multiple copies of mtDNA within each mitochondrion replicate and assort randomly. mtDNA segregates randomly to mitochondria as they divide, and the mitochondria are distributed randomly between the two daughter cells.
How do mitochondria divide?
Simple fission.
What is homoplasmy?
A pure population of mitochondria, either all wild type or all mutant.
What is heteroplasmy?
A mixture of mutant and wilt type mitochondria or their DNA within them.
Are most mitochondrial disorders produced by homoplasmy or heteroplasmy? What determines the severity of the disorder.
Heteroplasmy; severity depends on fraction of mutant mitochondria present in relevant tissues (must pass disease threshold)
Which one of these do mt disorders NOT show: Variable expressivity Incomplete penetrance variable age of onset Pleiotropy
Mt disorders show them all actually.
Describe the mitochondrial genetic bottleneck?
During oogenesis (in oocyte precursors), the number of mitochondria present is dramatically reduced (~100/cell) prior to expansion (~100k copies of mtDNA in mature oocyte), which produces variability of mitochondrial content in offspring.
Which is more prone to mutation, mtDNA or nuclear DNA and why?
mtDNA ~10X more prone to mutation than nuclear DNA. Due to ROS from OxPhos, lack of proofreading, and limited DNA repair mechanisms.
True or false: female heteroplastic for deletion mutations in mtDNA generally transmit the mutant mitochondria to her offspring.
False: the mechanism is unknown, but there is selection to NOT transmit mutant mitochondria to offspring.
How many copies of mtDNA are in each mitochondria and how many mitochondria are in each cell?
2-10 copies of mtDNA per mitochondrion, and hundreds of mitochondria per cell (thousands in oocyte)
What is the phenotypic threshold for heteroplasmic mitochondrial disorders?
60% for deletions and 90% for other mutations.
What does LHON stand for?
Leber hereditary optic neuropathy.
What mutation resutls in LHON?
Results from mutation in NADH dehydrogenase subunit 1 or 4 genes.
95% have one of three mutations, 2 of which are in subunit 1 (most and least sever), and the other in subunit 4 (intermediate).
Environmental (smoking and alcohol) and other genetic factors (being male) have an effect on the severity.
Are LHON mutations mostly hetero- or homo-plasmic?
homoplasmic
Why do LHON and MERRF worsen with age?
Mitochondrial function declines with age due to accumulated mutations.
Which of the following is not a symptom of LHON?
Initial painful vision loss
Blurred central vision
onset in twenties (can be later)
progression to blindness is rapid, affecting both eyes equally
may develop cardiomyopathy
Initial vision loss is painless.
