Mitochondrial Disorders and Inheritance

Question 1

mitochondrial DNA

Answer 1

circular chromosome, many copies in each mitochondria

encodes 13 respiratory chain peptides, 22 unique tRNAs and large and small rRNAs

Question 2

organization of mitochondrial genes

Answer 2

no intervening sequences, no 5’ or 3’ non-coding regions, and the peptide genes are separated by the tRNA genes

Question 3

causes of mitochondrial disorders

Answer 3

mutations in nuclear genes (1200 involved in mitochondrial function)

mutations in mitochondrial genes

Question 4

major systems affected by mitochondrial disorders

Answer 4

nervous system, skeletal muscle, cardiac muscle

Question 5

some common signs of mitochondrial disease

Answer 5

eye impairments, myopathy, weakness, exercise intolerance, cardiomyopathy, sensorinueral deafness, diabetes mellitus, optic atrophy, fluctuation encephalopathy

migrains, dementia, seizures, stroke-like episodes, ataxia, spasticity

Question 6

three most common mitochondrial gene point mutations

Answer 6

MELAS, MERRF, NARP

Question 7

MELAS

Answer 7

mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes

onset 2-10 years, characterized by seizures, recurrent headaches, vomiting, myopathy, development usually normal

Question 8

MERRF

Answer 8

myoclonic epilepsy with ragged red fibers

Question 9

NARP

Answer 9

neuropathy, ataxia, and retinitis pigmentosa

Question 10

Alpers-Huttenlocher Syndrome

Answer 10

caused by mutations in POLG which encodes the alpha subunit of polymerase gamma, needed for mtDNA replication

disorder is characterized by intractable seizures, progressive loss of brain function, and liver failure

disease onset is usually in childhood

Question 11

heteroplasmy

Answer 11

mitochondria contain many sets of DNA and each cell has many mitochondria

this is the result of mutations occuring in a mosaic form within different mitochondria in different DNA copies

the proportion of mtDNAs with the mutation may vary from mitochondrion to mitochondrion, from cell to cell, and from tissue to tissue

Question 12

threshold effect

Answer 12

a cell containing mutant mtDNA may function normally and only have problems if the proportion of mutant mtDNA exceeds a threshold

an organ may also not be affected until a proportion of its “mutant” cells exceed a threshold