11-26 Neurogenetics

Question 1

pattern of inheritance of mitochondrial DNA mutations

Answer 1

maternal inheritance; usu 1:1 male : female ratio

Question 2

where do mitochondrial genes reside

Answer 2

both w/in mitochondria DNA (37 genes) and in nuclear (~1500 genes)

Question 3

when should you suspect illness caused by mitochondrial DNA mutations?

Answer 3

—positive fam hx
—Mitochondrial disorders can affect muscle alone, muscle and brain, or multiple systems with variable involvement of the heart, kidney, liver, skeletal muscle, or brain.

Question 4

General mechanism of mtDNA diseases?

Answer 4

decr ATP —> cell death —> sx

—neurons especially susceptible

Question 5

functions of mitochondria

Answer 5

—ATP production
—Kreb's cycle
—Ca++ homeostasis
—capturing O2 radicals
—metabolism of amino acids, fatty acids, and steroids

Question 6

Why does mtDNA have high mutation rate?

Answer 6

> 10X frequency of nuclear mutations
—no introns; all mutations affect exons
—no protective histones; no effective repair mech
—Exposed to free O2 radicals(“smoke from the factory”; act as mutagens

Question 7

MERRF

Answer 7

Myoclonic Epilepsy Myopathy w/ Ragged Red Fibers

—point mutation at nt8344 and, or 8356 in tRNA lue

Question 8

NARP

Answer 8

Neuropathy,ataxia, Retinitis Pigmentosa, seizures, dementia

• pointmutationat8993 in the ATPase 6 gene

Question 9

MELAS

Answer 9

Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke - like episodes
—point mutation 3243 in the tRNA leu gene

Question 10

Why variable presentation of these mito dzs?

Answer 10

you can have normal mtDNA and mutant mtDNA even within the same mitochondria; mitochondria are separated in cytokinesis