Exam 3: Epigenetics II Flashcards Preview

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Flashcards in Exam 3: Epigenetics II Deck (49)
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1
Q

differentiated adult cells can be reprogrammed to form

A

induced pluripotent stem cells (iPSCs)

2
Q

epigenetic changes are associated with

A

cell differentiation

3
Q

what makes the difference for each specialized cell type in a human organism

A

you begin life as a fertilized single cell which contains all the genetic information for you to turn into you. same set of nucleotide seq is in every cell in the body and what makes the difference for each specialized cell type is the way genes get turned on/off via epigenetic controlling mechanisms

4
Q

in genomic imprinting, the expression of an allele depends on whether

A

it is inherited from the male or female parent

5
Q

in mammals, the epigenetic program is reset to a

A

to a male or female pattern during gamete formation

6
Q

what does it mean when parts of our genome are imprinted

A

different genetic behavior on the chromosome that came from your father compared to the one you got from your mother; alleles behave differently depending on which parent it came from

7
Q

genomic imprinting is the epigenetic phenomenon by which

A

certain genes are expressed in a parent-of-origin-specific manner.

8
Q

if the allele inherited from the father is imprinted =

A

methylated; it is silenced and only the allele from the mother is expressed ex

9
Q

t/f: if u have a mutant allele, depending on who got it from, it can have a big or no impact at all

A

true

10
Q

t/f: a chromosome region is differentially methylated depending on where you got it from (mom or dad)

A

true

11
Q

genomic imprinting in male mammals

A

male mammals at the time of gamete formation establish a methylation pattern on various regions around the genome that represent male pattern. genes get turned off if highly methylated

12
Q

genomic imprinting in female mammals

A

those same regions where males established a methylation pattern, those same regions are differentially methylated for females (some more or less depending on gene)

13
Q

2/3 thirds of prader-willi syndrome and angelman syndrome occurs via

A

a deletion (3 mill bps); occurs near the centromere on chromosome 15 and bounded by a set of highly repeated sequences and are sticky. is thought that during meiosis, those regions stick together and leaves a loop that gets broken in a common 3 mill bp deletion

14
Q

what is important about the region on chromosome 15 that gets deleted in prader-willi syndrome

A

region has multiple genes, several of which are only expressed by the father and one/two expressed by mother. those expressed by father is responsible for prader willi (SNRPN and snoRNAs deletion of genes)

15
Q

how connected SNRPN and snoRNAs deletion to prader willi

A

shown to contribute (KO mouse study) the phenotype of prader willi

16
Q

what is important about the region on chromosome 15 that gets deleted in angelman syndrome

A

region has multiple genes, several of which are only expressed by the father and one/two expressed by mother. if deletion comes from mother, the gene not expressed is UBE3A which codes for an enzyme that ubiquitinates many other genes (epigenetic modifier) that when not expressed gives you angelman syndrome

17
Q

1/3 of prader willi syndrome and angelman syndrome occurs via

A

uniparental disomy (inheriting 2 copies of a chromosome from one parent); 2 from mom and none from dad

18
Q

is uniparental disomy a deletion?

A

not a deletion, severe mutation in SNRPN (PWS) or UBE3A inactivation for angelman; functional alleles from dad is turned off in mom chromosomes thus no SNRPN expression and PWS

19
Q

reasoning behind nondisjunction in a fertilized egg in uniparental disomy

A

nondisjunction event in mother during meiosis; 2 chromosome 15s get into egg bc of nondisjunction from mother and if fertilized there will be 3 chromosome 15s. this is not compatible with life, thus it is thought that another nondisjunction event eliminates 3 chromosome

20
Q

probability of have PWS or angelman syndrome from uniparental disomy

A
  • 1 out of 3 chance that dad’s chromosome 15 will be eliminated thus no SNRPN thus PWS
  • 2 out of 3 chance mom’s chromosome 15 will be eliminated and this reestablishes the normal # of chromosomes and the right epigenetic modifications (compensation can have conseq of losing father’s chromosome 15)
21
Q

why do we have differentially methylated regions (DMR) in our genome?

A

particularly in mammals, difference in reproductive strategy; in males there are different pressures that exist than in females for genes to be scattered in environment. ex is a male deer is at an advantage to spread his seed in the population whereas the mother focuses on birthing one child per year (female strategy is to put on breaks and male is the foot on gas)

22
Q

about _ genes are imprinted in the human genome; _ maternal DMRs and _ paternal DMRs

A

60 genes; 37 maternal and 26 paternal

23
Q

environmental influence: _ can have a dramatic effect on methylation patterns in our genome

A

diet

24
Q

“there is a growing body of results indicating that many _ and _ aka _ are initiated and/or influenced by non-optimal _ programming often taking place _ in life

A

chronic metabolic and degenerative disorders and diseases aka ‘civilization diseases’ are initiated/influenced by non-optimal epigenomic programming, often taking place early in life

25
Q

what is the most important period of life

A

the first 1000 days of life (from conception into early infancy) as these 1st 1000 days are important in determining/setting a epigenetic program; affects phenotype for remainder of life

26
Q

pathways that are altered by epigenetic reprogramming result in _

A

dysregulation of important physiological functions contributing to metabolic syndrome and eventually type 2 diabetes

27
Q

inactivation of AKT2 and Tnfaip812 as a consequence of diet lead to

A

altered metabolic function and obesity

28
Q

maternal diet and fetus

A

maternal diet modifies the primate fetal epigenome; fetal histone H3 undergoes modification in response to a maternal high-fat diet

29
Q

epigenome-wide association study of body mass index, and the adverse outcomes of adiposity findings

A

epigenome-wide association shows that BMI is associated with widespread changes in DNA methylation ie distinction btwn methylation patterns in those who are lean vs obese

30
Q

does adiposity of parents have an influence on their child’s epigenetic genome?

A

yes; newborns of obese parents have altered DNA methylation patterns at imprinted genes

31
Q

cytosine methylation attenuates a _ to different degrees, resulting in _

A

attenuates pathogenic DNA sequence to different degrees, resulting in a spectrum characterized by yellow color, tumors, and obesity

32
Q

“the shifts in phenotype as measured by an increasing distribution of animals with yellow fur, and increasing wean weight, correlated with incr levels of

A

lead exposure

33
Q

CpG island methylator phenotype (CIMP) is characterized by

A

simultaneous hypermethylation of numerous CpG islands surrounding the promoter regions of several genes

34
Q

methylation of CpG islands in the promoter of tumor-suppressor genes could physically inhibit

A

binding of transcription factors

35
Q

by transcriptional silencing of theses genes, CIMP is believed to contribute to the onset and progression of

A

colorectal cancer (CRC)

36
Q

define epigenome

A

overall pattern of chromatin modifications possessed by each individual organism

37
Q

detecting DNA methylation (2)

A
  1. restriction endonucleases

2. bisulfite sequencing

38
Q

detecting histone modifications

A

ChIP

39
Q

tools for evaluating DNA methylation

A

bisulfite modifies cytosine residues on DNA converting from a C to a U which looks like a T when you sequence it. if cytosines are methylated, bisulfite does not work and remains a C thus bisulphite is a tool to see where methylated C are (PWS)

40
Q

tools for evaluating chromatin

A

ChIP-seq chromatin immuno-precipitation + next gene sequencing. methylated DNA is precipitated using an antibody that binds methylated DNA; finds regions of the genome assoc with chromatin modifications (histones)

41
Q

cancer =

A

epigenetic modifications; enhancer regions around specific genes = cancer = chromatin modifications = alter expression (oncogenes on and tumor suppressor genes off)

42
Q

how do we look at the “language” that leads to metastatic cancers

A

by looking at chromatin changes, changes regionally associated w/ acetylated lysines) cataloging them and their association w/ different kinds of genetic activations and formation of specific types of cancer

43
Q

haploinsufficiency and trim28

A

regulates imprinting; one copy means contributes to obesity

44
Q

2 novel mechanisms that contribute to phenotypic expression of CHDs:

A
  1. aberrant methylation of promoter CpG islands

2. methylation alterations leading to differential splicing

45
Q

folate is a source of

A

methyl groups that are needed for epigenetic programming (not enough = in trouble)

46
Q

epigenetic misprogramming is an essential component of

A

cancer development

47
Q

DNA methylation-based risk-prediction models provide

A

novel opportunities for risk-tailored screening and prevention of cancer

48
Q

in 2017 GWG company significance to epigenetics

A

first life insurance company to modify life insurance rates based on epigenetic pattern. epigenome reflects environmental experience and modifies gene expression throughout your entire body. insurance companies trust this research to use as a predictor to adjust ppls rates. ie this is a predictor of your life expectancy that GWG are willing to bet money on it

49
Q

how is the agouti mouse used as a biosensor for environmental modifiers of the epigenome

A

agouti gene controls distribution of dark pigment and agouti mice are genetically identical but vary greatly in their appearance. can we change the phenotype in the animal by alterations in the epigenome? model as an epigenetic biosensor to characterize nutritional and environmental factors affecting epigenetic gene regulation and subsequent adult phenotype.