Gen Mitochondrial Mastick Flashcards

1
Q

What are the tissues most dependent on oxidative phosphorylation (i.e need mitochondrias)?

A

heart, skeletal muscles, and CNS

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2
Q

Mitochondrial disorders often manifest as what?

A

myopathies (muscle),neuropathies (neurons), and encephylopathies (brain)

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3
Q

Mitochondrial dysfunction is also linked to what disorder?

A

diabetes mellitus

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4
Q

What is mitochondrial function influenced by?

A

1) Capacity for oxidative phosphorylation (nuclear and mito genes)
2) Tissue specific req.
3) age (cap. for OP decreases with age, i.e accumulation of mtDNA mutations)
4) Accumulation of somatic mtDNA mutations and degree of heteroplasmy

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5
Q

What do you call this:
The situation in which, within a single cell, there is a mixture of mitochondria (energy producing cytoplasmic organelles), some containing mutant DNA and some containing normal DNA

A

heteroplasmy

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6
Q

mitochondrial disorders are often (blank) or do not manifest until adulthood.

A

progressive

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7
Q

Mitochondrial function is sufficent at (blank) but deteriorates with age (normal) and accumulation of additional mutant alleles.

A

birth

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8
Q

How big is mtDNA and what does it encode?

How many nuclear DNA proteins are imported into the cell to participate in oxidative phosphorylation?

A

16.5 kb, encodes rRNAs, tRNAs, and 13 proteins

90

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9
Q

in mitochondrial disorders to males or females pass on their mutations?

A

females only

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10
Q

What are these major attributes of:
Usual recurrence risk:
affected mothers: 100% children inherit mutation.
affected fathers: 0% of children inherit mutation.
Transmission pattern: vertical; disease phenotype seen in generation after generation.
Sex ratio: equal numbers of affected males and females.
Other: progressive diseases, delayed age of onset,
highly variable expression (due to heteroplasmy).

A

Major attributes of mitochondrial inheritance patterns

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11
Q

(blank) inheritance is hallmark of mitochondrial inheritance.

A

maternal

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12
Q

all mitochondria come from the (blank)

A

egg

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13
Q

Name that disease:
Mitochondrial disorder with rapid loss of central vision due to death of the optic nerve. Delayed age of onset, 20-30 years old. 95% of cases caused by one of three missense mutations in a mitochondrial protein (mtDNA protein complex I).Heteroplasmy is rare. Expression is relatively uniform.

A

Leber’s hereditary optic neuropathy (LHON)

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14
Q

What is caused by one of three missense mutations in a mitochondrial protein (mtDNA protein complex I)

A

Leber’s hereditary optic neuropathay (LHON)

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15
Q

Name that Disease:
Four “canonical” features: Myoclonus, generalized epilepsy, ataxia, ragged-red fibers (RRF) in the muscle biopsy.

Frequent manifestations: Sensorineural hearing loss, peripheral neuropathy, dementia, short stature, exercise intolerance, optic atrophy

Mutation: single base changes in mitochondrial tRNA molecules that change their codon specificity.

A

MERRF (myoclonic epilepsy with ragged-red fiber)

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16
Q

How can MERRF be compatible with survival?

A

variable expression due to heterplasmy

17
Q

What is mosaicism caused by variable number of mutant mitochondria/cell

A

heteroplasmy

18
Q

What mutation makes tRNA put a wrong a.a in. So in this case only a very small number of tRNA expresses this mutation.

A

MERRF (myoclonic epilepsy with ragged-red fiber)

19
Q

(blank) has maternal transmission and variable expressivity?

A

MERRF

20
Q

What is this:
genetically distinct populations of mitochondria in somatic cells

due to differences in the ratio of mutant to normal copies of mtDNA.

causes mosaicism- distinct patches of cells (or whole tissues)
with different numbers of functional mitochondrial.

mosiacism- highly variable expression of disease, and
tissue specific differences from individual to individual.

A

heteroplasmy

21
Q

HOw many mtDNA molecules per mitochondria?

How many mitochondrias per cell?

A

2-10 mtDNA

10-100s

22
Q

What disease is this:
mutations in mitochondrial tRNA that change codon specificity.
Why is there heteroplasmy?

A

MERRF

So that it is hard to have a mito disease. i.e. you got back ups

23
Q

What diseases does this describe?
Mutant tRNAs: an incorrect amino acid is inserted into all mitochondrial proteins with this codon.

Normal tRNA molecules that recognize this codon and insert the proper amino acid must also be expressed (otherwise mitochondria would non-functional).

Severity of disease is determined by the ratio of mutant tRNA to normal tRNA and ratio of functional to non-functional mitochondria.

A

MERRF, MELAS

24
Q

In heteroplasmy, variation arises from what 2 things? What does this result from?

A
  • Genetic drift, selective advantage

* the mechanism by which mitochondria replicate and are distributed in cells during subsequent cell divisions.

25
Q

Replicative segregation:

Mitochondria replicate by division within a (blank) cell.
(blank) mtDNAs are replicated a variable number of times.
Each mitochondria inherits a (blank) of mt chromosomes.

A

somatic
Prior to division
variable number

26
Q

Describe the steps of mitochondrial replicative segregation.

A

replicate via division in somatic cell
mtDNA replicaed a variable number of times prior to cell division
Each mitochondria inherits a variable number of mt chromosomes

27
Q

What does this describe:
Each cell contains a population of different mitochondria, that are randomly distributed throughout the cell.

When daughter cells form by cytokinesis, they randomly inherit a variable number of mitochondria, which replicate after cell division.

A

mitotic segregation

28
Q

What does this describe:
Mitochondria replicate by division within a somatic cell. Prior to division, mtDNAs are replicated a variable number of times. Each mitochondria inherits a variable number of mt chromosomes.

A

replicative segregation

29
Q

Mutations in some nuclear genes responsible for either Oxidative phosphorylation components or for mitochondrial regulation can result in a phenotype that resembles a (blank); inheritance in these cases follows a typical autosomal dominant, autosomal recessive, or X-linked pattern. Although less common, these possibilities should be considered for recurrence risk counseling.

A

mitochondrial disorder

30
Q

Some mitochondrial DNA mutations (especially deletions) occur (blank) ; therefore, the family history may not show evidence of maternal inheritance.

A

sporadically

31
Q

(blank) children of mothers with mutant mitochondria inherit some mitochondria with mutant mtDNA, even if the mother does not express the phenotype herself; however, mothers with a higher proportion of mutant mtDNA have a higher risk of having clinically (blank) offspring.

A

All

affected