Chapter 3 Lecture

Question 1

what is epigentics -alter phenotype

Answer 1

study of modifications of the human phenotype not the genotype not dna mutations but modifications of phenotype or expressions that occur apart from DNA mutations

Question 2

what are the three various epigenetic mechanisms that cause genes to be expressed or silenced?

Answer 2

DNA methylation – a methyl group attaches to a cytosine

Histone modifications

RNA-based mechanisms

Question 3

Epigentic Mechanisms
DNA methylation

results from

what kind of gene

the DNA is less likely too?

Answer 3

SILENCES GENES*

Results from attachment of methyl group to cytosine

Renders genes silent
Prominent role in health and disease

Aberrant methylation can lead to misregulation of tumor-suppressor genes and oncogenes

When a gene becomes heavily methylated, the DNA is less likely to be transcribed into mRNA

methalyn gene gone wrong can mean onco (cancer genes can be expressed) tumor suppresor genes can get silenced

Question 4

Gene makes up

Answer 4

RNA or protein

Question 5

If it gene gets silenced

Answer 5

then the RNA or protein doesn’t get made

Question 6

Epigentic Mechanisms

Histone Modification
what are histones?

what does it include?

what is chromatin?

Answer 6

Histones
Proteins that facilitate compaction of DNA into the nucleus of a cell

Histone modifications include histone acetylation and deacetylation to the end of a histone protein

Chromatin
DNA in association with histones
Critical role in determining development of cells

Question 7

in histone modification DNA doesn’t..?

Answer 7

Histone has been modified, doesn’t associate with DNA is a usual way
Changes how that DNA is expressed
Epignetic
EFFECTS DNA

Question 8

Epigenetic Mechanisms

RNA-Based Mechanisms

describe noncoding
describe miRNAs

Answer 8

Noncoding RNAs (ncRNAs) doesn't code
Role in RNA splicing and DNA replication
“Sop up” "cleaning up" complementary RNAs, extra RNA's and prevents their functions

MicroRNAs (miRNAs)
Modulate (change/affect) the stability and translational efficiency of existing messenger RNAs
Specific (won’t bind to all messengers can effect sequences of mRNAs) and general

-dont change gentetic code of RNA but can effect how mRNA

need both DNA an RNA to make protein

Oncomirs
miRNAs that stimulate cancer development

Question 9

epigentics

Answer 9

genes in the genotype that can cause for it

Question 10

interaction between genotypes/environment, how does that show in the phenotype, how does it affect offspring

Answer 10

epigentics, change pheotype based of genotype, expressed or silenced of a gene- that gene ends up making rna or protein use to code, if gene is silenced then rna or protein doesn’t get made, doesnt mean it wasn’t made but that particular gene isnt made because it gets silenced

Question 11

RNA-Based Mechanisms

Answer 11

Doenst change the code but can effect how it does it work, how it translates proteins
In expression in the phenotype because it causes it changes the effects in the RNA

Question 12

Epigenetics and Human Development

Embryonic stem cells

Totipotent

Specific genes are expressed only in the cells and tissue types in which their gene products typically function

Answer 12

Totipotent
Able to give rise to all cell types of an organism

Specific genes are expressed only in the cells and tissue types in which their gene products typically function
Factor VIII expression in hepatocytes
Dopamine receptor expression in neurons

Question 13

Epigenetic modification enables cells to

Answer 13

achieve diverse functions

Question 14

All cells in an individual contain almost

Answer 14

same information

Question 15

“Housekeeping” genes remain transcriptionally active in almost all cells, support & maintain all cells

Answer 15

Encoding histones
DNA and RNA polymerases
Ribosomal RNA genes

Question 16

Genomic Imprinting means..

Answer 16

a silencing phenomenon of some genetic material, and privleging of others

Question 17

example of gene imprinting

Answer 17

Copy inherited from father is active while copy inherited from mother is inactive (silenced)
are said to be “imprinted”

Question 18

Transcriptionally silenced genes

Answer 18

are said to be “imprinted”

Question 19

Biallelic expression is?

Answer 19

Maternal and paternal inherited genes contribute to offspring phenotype

Question 20

Monoallelic expression is?

Answer 20

Maternal copy randomly chosen for inactivation in some cells, paternal copy in others

Question 21

Imprinted

Answer 21

Copy inherited through sperm or egg is inactivated and remains inactive for life

Question 22

Imprinter

Answer 22

inherit an inactivated gene

A relatively small number of our genes are effected by gene imprinting

Question 23

Genetic conflict hypothesis- explain?

Answer 23

Imprinting of maternally inherited genes tends to reduce offspring size

Imprinting of paternally inherited genes tends to increase offspring size

Question 24

Prader-Willi and Angelman syndromes,Genomic Imprinting (Cont.)
EXAMPLES OF PHENOTYPE DEPENDING UPON WHETHER OR THE MATERNAL OR PATERNAL ALLELE IS EXPRESSED AT A SPECIFIC LOCUS OR NOT

dna is the same, pheno is different in these two diseases

Answer 24

Deletion of 4 million base pairs of long arm of chromosome 15

Severely mentally challenged, seizures, ataxic gait
Indistinguishable at DNA sequence level

Question 25

Genomic Imprinting Manifestations of Prader-Willi syndrome if inherited from father

Answer 25

Short stature, hypotonia, small hands and feet, obesity, mentally challenged

Question 26

Genomic Imprinting Manifestations of Angelman syndrome if inherited from mother

Answer 26

Severely mentally challenged, seizures, ataxic gait . The reason for this difference is that different genes in this region are normally imprinted (inactivated) in the copies of 15q transmitted by the mother and the father.

Question 27

``` Genomic Imprinting (Cont.) Beckwith-Wiedemann syndrome ```

Answer 27

20%-30% caused by inheritance of two copies of a chromosome from father and no copies from mother Overexpression of active insulin-like growth factor 2 (IGF-2) Manifestations present at birth Large for gestational age, neonatal hypoglycemia, large tongue, creases on earlobe, omphalocele

Question 28

``` Genomic Imprinting (Cont.) Russell-Silver syndrome ``` cause?

Answer 28

One third of cases caused by imprinting abnormalities of chromosome 11p15.5 10% caused by maternal uniparental disomy(two alleles) Downregulation of active IGF-2 causes diminished growth

Question 29

Genomic imprinting

Answer 29

DNA is the same, it's just what's left imprinting mom or imprint of dad

Question 30

know about imprinting is

Answer 30

is the silencing whether to know if its from mom/dad what you inherit, but then what you look like,phenotype, what is expressed depends on which one is silenced, when you get a gene from mom and dad, one of them is going to be sileneced, not going to go which sileneced in such away that it will effect the phentype

Question 31

Relationship between nutritional deprivation and disease on one or more generations is largely unknown, explain inslin answer

Answer 31

Insulin-like growth factor 2 (IGF-2) gene may have undergone epigenetic modifications due to nutritional deprivation In utero exposure to chemicals may lead to similar epigenetic modifications

Question 32

Epigenetics and Maternal Care altertation to methylation states lead to... epigentic processes stores up.. info

Answer 32

Alteration to methylation states could help explain why exposure to stress early in life can modulate behavior in adulthood **impact or racism on women** Epigenetic processes “store up” information about the environment and resulting modifications in genes can affect behavior later in life

Question 33

Epigenetics and Ethanol Exposure During Gestation Fetal alcohol syndrome - can show a phenotype a birth

Answer 33

Alcohol exposure in utero can impact DNA methylation states of various genomic elements Exposure to ethanol impairs cultured stem cells’ ability to differentiate into functional neurons Ethanol exposure in utero may repress fetal expression of the DNA methyltransferases

Question 34

Epigenetic Disease in Context of Genetic Abnormalities Fragile X syndrome

Answer 34

Arises through gain of abnormal methylation Large cytosine-guanine (CG) repeat in FMRI promoter Disease can be present in males with the large repeat and absent in others with similar large repeats Acquisition of methylation-based silencing at FMRI is stochastic

Question 35

Genomic imprinting

Answer 35

imprinting is best described as what genes are silenced depending on which parent transmits them

Question 36

Epigenetic Disease in Context of Genetic Abnormalities (Cont.) -talked about it earlier as a sex-linked inherited disorder, if it doesn't show up as a phenotype because of epigentics mechanism which can cause damage to the.. ? Fascioscapulohumeral muscular dystrophy (FSHMD)

Answer 36

Arises through loss of normal methylation Deletion of a nucleotide repeat in the DUX4 gene -results from mutational expansion at the FMR1 locus followed by epigentic inactivation

Question 37

Twin Studies reason for phenotypic differences? epigentic patters are

Answer 37

As twins age there are increasingly substantial differences in methylation patterns of DNA sequences on somatic cells Often reflected in increasing numbers of phenotypic differences The greater the lifestyle differences the larger the number of differences in methylation patterns. **Suggest epigenetic patterns are important part of aging process**

Question 38

Molecular Approaches to Understand Epigenetic Disease

Answer 38

scientists are trying to use mechanisms to snip out and idetify epigentic changes and how epigentic information gets coded in modification to the DNA molecules Epigenetic information is encoded by chemical modifications to DNA molecules Various strategies are used to try to understand those modifications Bisulfate conversion prior to DNA sequencing Histone modification states assayed through use of antibodies

Question 39

Epigenetics and Cancer DNA Methylation what does this mean for tumor cells? vs tumor suppressor genes

Answer 39

Tumor cells typically exhibit genome-wide decreased methylation (hypomethylation), **meaning they can increase oncogene activity and thus increase tumor formation** Tumor-suppressor genes often hypermethylated, meaning they are less able to inhibit tumors from forming RB1 gene—retinoblastoma BRCA1 gene—some inherited breast cancer

Question 40

Epigenetics and Cancer (Cont.) | miRNAs

Answer 40

Ordinarily encode small RNA molecules that bind to ends of mRNAs This degrades the mRNAs and prevents their translation Associated with tumor metastasis

Question 41

Epigenetics and Cancer | When microRNA genes are methylated..

Answer 41

their mRNA targets are overexpressed

Question 42

Epigenetics and Cancer Hypermethylation of some miRNA subgroups is associated

Answer 42

with tumor development

Question 43

Epigenetics and Cancer (Cont.) what's being screened?

Answer 43

Epigenetic screening for cancer, such as looking for mis-regulated miRNAs, shows promise as a tool for early cancer diagnosis

Question 44

Epigenetics and Cancer (Cont.) Strategies for treatment of epigenetic disease DNA demethylating agents Histone deacetylase inhibitors miRNA coding

Answer 44

Pharmaceutical agents may reverse changes associated with disease phenotype DNA: 5-azacytidine to treat leukemia and myelodysplastic syndrome histone:Breast and prostate cancer miRNAcoding: Target genes that cause cancer