Genetics 3.12 Flashcards Preview

NMSK-B III > Genetics 3.12 > Flashcards

Flashcards in Genetics 3.12 Deck (33):
1

Explain replicative segregation, heteroplasmy, and the mode of inheritance of mitochondrial disorders

Multiple copies of the nucleoid genome do not follow diploid characteristics, but follow prokaryotic methods

2

Provide an explanation for the pleiotropy of mitochondrial disorders

ATP production is critical in many different cellular processes, and alteration of this production would therefore have pleitropic effects

3

Differentiate between mutations within the mitochondrial and nuclear genomes in the pathogenesis and inheritance of mitochondrial disorders

Mutations in nuclear DNA can be inherited from both parents, but mtDNA only from mom

4

Describe strategies to treat mitochondrial disorders and to prevent their transmission

We can’t currently effectively treat mitochondrial disorders, nor prevent transmission

5

Describe the role of mitochondria within cells and their contribution to aging and neurodegenerative diseases

Mitochondrial dysfunction leads to ROS buildup and decline in ATP production

6

How many mitochondria are there in a cell?

anywhere from 1-1000s; divide by budding

7

What is the endosymbiotic theory?

explains how mitochondria can be modeled as a trapped prokaryoke surrounded by a modified internal membrane

8

What is the role of mitochondria in a cell?

convert small carbon sources to ATP and CO2 utilizing O2
**prok. genome
**viral DNA replication machinery

9

What is a nuceoid?

circular, stable DNA in a prokaryote; mitochondria

10

What is the inheritance of mitochondrial defects?

maternally-derived

11

What is replicative segregation?

-unequal distributions of mtDNA nucleoids during mitochondrial replication
-due to stochastic processes
-heteroplasmy creates differing populations of mt genomes in active tissues

12

What is the definition of stochastic?

outcome of randomly determined based on the theory of *probability*

13

Do mitochondria have control of DNA segregation?

No; mitochondria within the same cell may have different DNA "rings" (nucleoids)
**there are different mt DNA within the same miochondria

14

What is heteroplasmy?

mixture of wt and dysfunctional/mutated mitochondria within progenitor cell/tissue

15

What is the after-effect of heteroplasmy?

differing populations of cells within a tissue

16

How is a disease state influenced by heteroplasmy?

X% of cell's mitochondria are diseased; if it crosses this threshold, a disease will present

17

How does mitochondrial genetics differ from Mendelian genetics?

-prokaryotic structure
-large copy number of mitochondrial chromosome
-method of inheriting mitochondrial chromosomes

18

Where are the genes which code for the mitochondrial replication, transcriptional, and translational machinery located?

-some on mitochondria [follows maternal copy # inheritance]

-some in cell's genome in nucleus [follows Mendelian inheritance]

19

Do mitochondrial chromosomes undergo recombination?

No, there are no different mitochondria in the cell to undergo recombination with
**once mutation occurs, it stays within that lineage

20

Where are most mitochondrial genes held?

nuclear DNA

21

What are the rates of mutation and recombination in mitochondrial DNA?

low
rare

22

How do mitochondrial genomes act in terms of inheritance?

haplotypes (gene clusters inherited as a group)

23

Which tissues would be most susceptible to disruption by mitochondrial dysfunction?

nerves and skeletal muscle (uses a lot of ATP for its function, which is produced by mitochondria)

24

What are ragged red fibers?

-grouping of malfunctioning mitochondrion below the plasma membrane of mitochondrial myopathies
-Gomori Trichrome to visualize
-alters muscle fiebr contours; gives ragged appearance

25

What is MERRF Syndrome?

Myoclonic Spilepsy with Ragged Red Fibers;
1) Progressive myoclonic epilepsy
2) Exercise intolerance/lactic acidosis
3) Hearing loss and poor night vision

26

What is MELAS Syndrome?

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes;
1) muscle weakness/pain
2) headache, seizures, vomiting
3) stroke-like symptoms as they approach middle age
**variance due to heteroplasmy

27

What is KSS?

Kearns-Sayre Syndrome;
1) eyelid, extra-ocular muscles affected
2) retinopathy, cardiac conduction problems, endocrinopathies

28

What is Leigh Syndrome?

-Nuclear DNA mutation (no heteroplasmy);
1) bilateral lesions in brainstem, basal ganglia, cerebellum
2) demylination, gliosis, necrosis
3) dystonia, nystagmus, ANS dysfunction, deafness

29

What is the treatment of mitochondrial dysfunctions?

highly limited and ineffective
-lifestyle treatments
-antioxidant and pyruvate therapy
**best (untried): spindle transfer of nuclear DNA to a new egg**

30

What is the relationship between mitochondrial dysfunctions and age?

accumulated dysfunctions of mitochondria have been implicated in aging

31

What evidence supports that the degeneration of tissues seen in aging may be somewhat due to mitochondrial aging?

-*increased reactive oxygen species (ROS) production*
-decline OxPhos
-structural loss in mitochondria
-accumulated mtDNA mutations

32

What is sarcopenia?

-irreversible loss of muscle fibers in the elderly
-due to mitochondrial defects accumulated over time (ROS production)

33

What single word should you associate with mitochondrial defects?

pleiotropy