WEEK 10 (Extranuclear Inheritance) Flashcards
Where can genetic material also be found in the cell apart from the nucleus?
Mitochondria & Chloroplasts
What is Extracellular inheritance/Cytoplasmic inheritance?
Inheritance of organellar genetic material in mitochondria and chloroplasts which are found within the cytoplasm of cells
What are the several varieties of extranuclear inheritance?
- ORGANELLE HEREDITY = DNA contained in mitochondria or chloroplasts determines certain phenotypic characteristics of the offspring (e.g uniparental transmission of organelles through egg cell)
- INFECTIOUS HEREDITY = SYMBIOTIC/PARASITIC association with a microorganism where an inherited phenotype is affected by the presence of the microorganism in the cytoplasm of host cells
- MATERNAL EFFECT on the phenotype = Nuclear gene products are stored in the egg and transmitted through the ooplasm to offspring
Describe Extranuclear inheritance
Transmission of genetic information to offspring through the cytoplasm rather than through the nucleus, most often from only one of the parents
Describe mitochondrial DNA
- Double-stranded and closed circle
- Smaller than Chloroplast DNA
- Introns are absent
- Gene repetitions are present
What does human mtDNA encode?
- 2 ribosomal RNAs
- 22 transfer RNAs
- 13 polypeptides
[all essential to the oxidative respiration functions of the organelle]
What is the difference between Chloroplast DNA and Mitochondrial DNA?
CHLOROPLAST DNA
Introns = present
MITOCHONDRIAL DNA
Introns = absent
Describe mitochondrial inheritance
- Transmitted only through the mother
- All offspring of affected females may show signs of disease
- Variable expression in a population or even within a family due to heteroplasmy
What is Heteroplasmy?
Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrially inherited disease
In order for a human disorder to be attributable to genetically altered mitochondria, what criteria must be met?
- Inheritance must exhibit a maternal rather than a Mendelian pattern
- The disorder must reflect a deficiency in the bioenergetic function of the organelle
- There must be a mutation in one or more of the mitochondrial genes
What are the two ways that mitochondrial diseases occur?
- Mitochondrial mutations are transmitted from mother to offspring via the cytoplasm of the egg
- Mitochondria mutations occur in SOMATIC CELLS and accumulate as the person ages
[Mitochondria are susceptible to DNA damage -> When more oxygen is consumed than is actually used to make ATP, mitochondria tend to produce FREE RADICALS that damage DNA -> Unlike nuclear DNA, mitochondrial DNA has very limited repair abilities and almost no protective ability against free radical damage]
Describe Myoclonic Epilepsy and ragged-red fiber disease (MERFF)
A maternally inherited mitochondrial disorder where only the offspring of affected mothers inherit the disorder and express ataxia, deafness, dementia and epileptic seizures. “Ragged red” skeletal muscle fibers exhibit blotchy red patches resulting from the accumulation of diseased mitochondria in the sarcolemma of the muscle fiber.
MUTATION: Gene encoding tRNALys (tRNA that delivers Lysine during translation) contains an A-to-G transition within its sequence -> Genetic alteration interferes with the capacity of translation within the organelle
Cells of affected individuals exhibit HETEROPLASMY -> contains a mixture of normal and abnormal mitochondria -> Mutation is not lethal
SYMPTOMS:
- Myopathy
- Lactic acidosis
- CNS disease
- Ataxia
- Deafness
- Dementia
- Epileptic seizures
What causes the neurological symptoms of MERFF?
Brain function, which has a high energy demand, is affected by the disorder
Describe Leber’s Hereditary Optic Neuropathy (LHON)
A maternally inherited mitochondrial disorder that causes mtDNA lesions. Mutations in the mitochondrial gene encoding a subunit of NADH DEHYDROGENASE disrupts normal oxidative phosphorylation leading to sudden bilateral blindness.
Cell death in OPTIC NERVE NEURONS -> Subacute bilateral vision loss in teens/young adults (90% males), usually permanent -> Also leads to neurologic dysfunction and cardiac conduction defects
