WEEK 4 (STUDY GROUP)

Question 1

mito disease affects organs with ____ and _____

Answer 1

high energy requirements and high metabolic

Question 2

what are examples of signs of mito disease

Answer 2

affects nervous system (brain), muscle, heart muscle

Question 3

what is progression of mito disease

Answer 3

step wise

Question 4

describe mito dna

Answer 4

circular, continous, no 5 or 3 uncoding regions, nuclear proteins help make mito proteins BUT mito dna doesn’t impact nuclear DNA

Question 5

homoplasmy vs heteroplasmy

Answer 5

homo is that all the mtdna is the same (either all wild or mutant) vs. hetero is a mixture of wild and mutant

Question 6

bottleneck effect

Answer 6

there are variable amounts of mutant dna in each cell and each mitocondria; there is asymmetric segregation of mutant mtdna during cell division; variable amount is passed along; increased mutant dna is assoc. with severe disease

Question 7

threshold effect

Answer 7

above a certain % of mutant dna means disease phenotype affect (different thresholds for different genes)

Question 8

important mitocondrial functions that happen inside

Answer 8

TCA cycle in the matrix, oxidative phosphorylation on the inner membrane

Question 9

if you suspect a mitochondrial disorder in oxidative phosphorylation what would be a sign

Answer 9

increased lactate (lactic acidosis) bc aerobic metabolism of pyruvate is not occurring

Question 10

most of mtDNA inheritance – what does it look like for offspring and who can pass it down

Answer 10

any offspring can have it; only passed down through female

Question 11

qualitative trait vs quantitative

Answer 11

Qualitative traits are those that have a defined cutoff; you either have a cleft lip, or you don’t. Quantitative traits vary in their intensity and do not lend themselves to the rigidity of categorizing a trait as present V absent. An example could be (qualitative) cleft lip v. (quantitative) Intelligence.

Question 12

Define: epigenetics

Answer 12

The study of heritable changes in gene expression without a change in the actual DNA sequence

Question 13

What is the role of epigenetic in cell-type specificity?

Answer 13

Between fertilization and implantation of the zygote: demethylation and loss of most epigenetic modifications (with the exception of imprinted regions) from the genome –> the zygote is now totipotent (has the potential to develop into every cell in the body)

During development, DNA methylation and histone modifications occur that gradually restrict the number of cell types a particular cell can become

Question 14

What are the 2 primary types of epigenetic modifications?

Answer 14

DNA methylation, histone modifications

Question 15

What are the 2 mechanisms in which epigenetic disorders cause disease? Give examples of each

Answer 15

1. Pathogenic variants alter chromatin directly. Examples: beta thalassemia, fragile X syndrome, congenital limb malformation disorders, fascioscapulohumeral muscular dystrophy-1 (FSHD1)
2. Pathogenic variants in genes that regulate the epigenetic machinery. Examples: Kabuki syndrome, fascioscapulohumeral muscular dystrophy-2 (FSHD2)

Question 16

Monoallelic expression

Answer 16

when expression of a particular gene occurs from only one of two alleles.

Question 17

Genomic imprinting

Answer 17

When only one of the two alleles at a particular locus are expressed, and this is dependent on the parent that that gene was inherited from.

Question 18

Maternally imprinted

Answer 18

the gene is NOT expressed from the maternal allele, but instead is subject to silencing by DNA hypermethylation and other changes that reflect a closed chromatin conformation.

Question 19

Paternally imprinted

Answer 19

the gene is NOT expressed from the paternal allele, but instead is subject to silencing by DNA hypermethylation and other changes that reflect a closed chromatin conformation

Question 20

Imprinting control region (ICR)

Answer 20

Locus that determines and controls imprinting within a particular region, also called the imprinting center (IC)

Question 21

Uniparental disomy (UPD)

Answer 21

The inheritance of both homologues of a particular chromosome from a single parent.

Question 22

Heterodisomy

Answer 22

The inheritance of both grandpaternal chromosomes from one parent and a single chromosome from another, resulting in triomsy for that chromosome. ‘Trisomy rescue’ then occurs where one of the chromosomes is deleted early in the post-zygotic embryo to ensure the normal diploid number of chromosomes. Thus the individual is heterozygous for many alleles on that chromosome, but they are both from either the maternal or paternal lineage.

*It is possible for the single chromosome for the other parent to be kicked out, such that a person has both chromosomes from one parent.

Question 23

Isodisomy

Answer 23

Is the result of ‘monosomy rescue’, in this instance, the post-zygotic embryo contains only a single copy of a particular chromosome, which undergoes duplication, such that each cell contains two exact copies of that chromosome. Thus the individual will be homozygous for all alleles on that chromosome.

Question 24

Genomic imprinting and uniparental disomy disorders

Answer 24

Prader-Willi Syndrome (PWS) and Angelman syndrome (AS)

Both PWS and AS are caused by abnormalities at 15q11-13. This region contains several genes that are subject to genomic imprinting.

Prader: paternally expressed; maternally imprinted; paternal variants/deletions

Angelman: maternally expressed; paternally imprinted; maternal variants/deletions