Mitochondrial Genetics

Question 1

mito genome

Answer 1

37 genes
13 for proteins
24 for parts of machinery that helps make those proteins

mito dna is passed on to next gen mitos

Question 2

mutations in mito dna can cause disease why?

Answer 2

–there is no repair mechanism for mito dna

Question 3

types of mutations in mito genome

Answer 3

–no recombination mutations happen

2 major mutations

1. point mutations in tRNA
2. deletions and rearrangements

Question 4

point mutations in mtDNA tRNA genes

Answer 4

leads to MELAS & MERFF

Question 5

deletions and rearrangements of mito genome

Answer 5

leads to KSS & CPEO

Question 6

mito myopathies

Answer 6

a mito myopathy is a muscle disease caused by mito dysfunction
or
degeneration of muscle fibers caused by accumulation of abnormal mito

Question 7

characteristics of mito disorders

Answer 7

clinical variability

age related progression of disease

Question 8

mito genetic diseases come in __ major types

Answer 8

4

Question 9

major mito genetic diseases discussed

Answer 9

1. MERRF
2. MELAS
3. KSS
4. CPEO

(5. LHON)

Question 10

MERRF

Answer 10

myoclonus epilepsy w/ ragged red fibers

Question 11

MELAS

Answer 11

mito encephalopathy, lactic acidosis and stroke-like episodes

Question 12

KSS

Answer 12

kearns-sayre syndrome

Question 13

CPEO

Answer 13

chronic progressive external opthalmoplegia

Question 14

LHON

Answer 14

leber hereditary optic neuropathy

blindness in late adolescence
muscles not affected

Question 15

red ragged fibers

Answer 15

aggregates of abnormal mito forming red sarcolemmal blotches called this

Question 16

characteristics of mitos

Answer 16

• -inherited from mother
• -self replicate
• -rate of mutation is higher than nuclear genes (10x)
• -multiple mito in cells

Question 17

heteroplasmy

Answer 17

when mtDNA mutation occurs in some mito

resulting in a mix of healthy and abnormal mitos in a cell

segregation in cell division is random

Question 18

threshold effect

Answer 18

need a certain level of abnormal mito vs. normal for disease to occur

Question 19

tissues affected by mito mutations

Answer 19

tissues that require more energy than others

such as muscle and nervous tissue

brain/cns, heart and skeletal muscles

Question 20

mito inheritance rules

Answer 20

only females pass on mito to their offspring

mitos are given to fetus in the egg only

a mother who is abnormal does not always pass disease on to child but has high risk of doing so

an affected father will never pass it on to his kids

Question 21

MERRF mutations

Answer 21

85% due to A to G mutation at position 8344

5% due to G to C at position 8356

Question 22

MERRF clinical presentation

Answer 22

involuntary jerking
epilepsy
ataxia
ragged red fibers
seizures
dementia

Question 23

MERRF age related progression

Answer 23

the older you are the higher the mutation rate the more severe the disease

Question 24

MELAS clinical presentation

Answer 24

lactic acidosis
stroke like episodes
ragged red fibers
seizures
blindness
vomiting

Question 25

MELAS progression

Answer 25

onset between 2 and 10 yrs typically caused by A3242G mutation in tRNA-Leu

Question 26

KSS clinical presentation

Answer 26

retinitis pigmentosa -- degenerative eye disease leading to blindness - cardiac conduction abnormality - cerebellar ataxia - cerebral spinal protein level above 100

Question 27

KSS other presentations

Answer 27

``` optic atrophy hearing loss dementia seizures cardiomyopathy lactic acidosis ```

Question 28

KSS mito mutations

Answer 28

85% due to mtDNA rearrangements including duplicated, deleted, or insertions

Question 29

CPEO presentation

Answer 29

ragged red fibers | ptosis -- dropping of eyelid

Question 30

LHON presentation

Answer 30

mito defects only affect optic nerve no muscle involvement vision loss beginning in 20s-30s and is rapid

Question 31

LHON mutation

Answer 31

mtDNA mutations in coding genes of complex I proteins single base pair substitution

Question 32

more severe mutations are associated w/

Answer 32

more severe neurological symptoms

Question 33

``` summary of mutations MERRF MELAS KSS CPEO LHON ```

Answer 33

1. tRNA 2. tRNA 3. mtDNA rearrange 4. mtDNA rearrange 5. mtDNA genes - complex I - single bp subsitution