Mitochondrial and Forensic Genetics - RM Flashcards
What processes do mitochondrial DNA mutations affect? What tissues is it most serious in?
oxidative phosphorylation, most serious in CNS and muscle
neuropathy, encephalopathy, myopathy
Is mitoDNA sufficient for full function of mitochondria?
no, needs nuclear genes too to help govern certain processes
What type of inheritance do most mitochondrial diseases show?
matrilineal inheritance because mitochondria are transplanted in the egg’s cytoplasm to all offspring
What does homoplasmy mean?
population of mitochondria all having the same genetic composition
If mother is homoplasmic and affected by a disease, what will the result be in her offspring?
all of her children will inherit the disease from the mother (any variation between children and mom is result of de novo mutation)
What is heteroplasmy?
heterozygosity for one or more cytoplasmic genes, 2 or more different populations of mitochondria present in cell
If mother is heteroplasmic and affected by disease, what will the result be in her offspring?
difference in expression of same disease within a family because mom can transmit different proportions of mutant/normal cells to each offspring
for any given cell to express dysfunction, what % of mutant mitochondria must be in that cell?
85%
Is there variability in expression of mutant mitochondria in certain tissues?
yes, affects whether disease manifests or not
Why are mitochondrial disorders often progressive with late onset?
due to increases in number of mutations per cell and number of mutant cells over time
What is replicative segregation?
as cells divide, relative proportions of mutant mitochondria change over time (can increase or decrease number of mutants in clone)
Why do mitochondrial disorders usually get worse if technically through replicative segregation, they could eliminate the mutation?
there is high mutation rate in mitoDNA leading to more acquired mutations too which proliferate
Why is there a range of phenotypes in the pedigree?
different levels of mutant mitochondria since distribution of mitochondria to daughter cells during somatic division is not precise
What disease has ragged red fibers in muscle biopsy?
MERRF (Myoclonic Epilepsy with Ragged Red Fibers)
What region is tested in DNA analysis? what is looked at?
hypervariable minisatellite regions tested for sequence variability with high degree of polymorphism
