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CMMB Midterm 1 > CMMB final material > Flashcards

CMMB final material Flashcards

1
Q

The human genome main

A
  • two copies in every somatic cell
  • one copy in gametes
  • 22 autosomes and 2 sex chromosomes
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2
Q

Genetic variation in normal populations

A

a) chromosomal level
b) CNV/person
c) single nucleotide level

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3
Q

Genetic variation also causes disease

A

a) whole chromosome (aneuploidy) Trisomy 21 (Down’s Syndrome)
b) Partial chromosome imbalance: seen by FISH
c) single nucleotide substitutions= Achondroplasia (little people)

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4
Q

polymorphism

A

any change within a popualtion thats >1%

-rare variant- anything less than 1%

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5
Q

Types of DNA polymorphisms

A
  • single nucleotide insertion/deletion
  • microsatellite
  • minisatellite
  • copy number variant (CNV)
  • single nucleotide variant (SNV)
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6
Q

single nucleotide insertion/deletion

A
  • many in the genome, unstable through generations

- unstable because DNA reproduces a second strand that can slip causing gain/lost od nucleotides

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7
Q

Microsatellites

A
  • repeat units are 2-5 nucleotides in length
  • also called Short Tandem Repeat (STR)
  • certain number of repeats= many alleles in normal populations
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8
Q

Microsatellite uses

A
  • DNA fingerprinting (everyone has different number of repeats)
  • also half are passed off to kids
  • disease: finding where those genes are located
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9
Q

Minisatellites

A
  • repeat units are 10-100 nucleotides in length
  • also called VNTR–> variable number of tandem repeat units
  • Southern blot used
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10
Q

Copy Number Variation

A
  • deletions and duplications
  • range from 200 to >2000000 nucleotides
  • usually 0-4 copies
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11
Q

Single nucleotide variants (SNVs)

A
  • most common type of sequence variation
  • more than 3000000/person
  • many different effects: benign to disease-causing
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12
Q

Origins of Sequence Variation/Mutations

A
  • replication errors

- DNA damage (deamination, depurination, demethylation) also by mutagens

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13
Q

Large deletion/duplication mechanisms

A
  • more likely to happen in repetitive sequences

- if homologous sequences are very similar wrong ones can align together

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14
Q

CMT1a

A

Charcot-Marie-Tooth

  • duplication
  • progressive peripheral motor and sensory neuropathy (numbness/weakness)
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15
Q

HNPP

A
  • Hereditary Neuropathy with Liability to Pressure Palsies
  • peripheral nerves are unusally sensitive to pressure and results in numbness, tingling, and/or loss of muscle function

-deletion

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16
Q

Haemophilia A

A
  • inverted repeats
  • found in 45% of patients

normal is
1-21,22,23

affected
22, 21-1, 23

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17
Q

Translation refresher

A

a codon= 2 base pairs (total=64 codons)

-each codon= 1 amino acid
20AA
3 STOP: UGA, UAA, UAG
1 START: AUG (met)

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18
Q

Nomenclature (DNA level)

A

nucleotide #1: A in ATG (start)

upstream nucleotides are negative eg) 2 bps to the left= -2

downstream coding nucleotides numbered normally–> introns are skipped

amino acids numbered starting with the start codon=1

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19
Q

Mutation Types

A 
A) Nucleotide Substitutions 
-AA effect: 
synonymous (silent) 
non synonymous (missense) 
nonsense 
splicing effects

B) duplication/deletion

  • small
  • large (one or more exons)

C) dynamic mutations

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20
Q

Synonymous (silent)

A

-DNA sequence change doesnt change the actual AA that is coded

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21
Q

Non-synonymous (missense)

A

-DNA sequence change; CHANGES the AA

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22
Q

Nonsense

A

premature stop codon

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23
Q

-ie) CTA–> CTG both are LEU

if this is found as the 325th AA in a protein how would you write that?

A

p.Leu325Leu

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24
Q

CTG–>CCG (LEU–> PRO)

if this as the 112th AA in a protein how would you write that?

A

p.Leu112Pro

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25
Q

TTA–> TAA Leu–> Stop

if this is found as the 33rd AA in a protein how would you write it?

A

p.Leu33*

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26
Q

Read-through (nonstop)

A

TGA–> GAA stop–> GLY

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27
Q

Mutated start codon

A

DNA seq changes the AA thats coded

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28
Q

ATG–> GTG Met–> VAL

A

p.Met1Val

this is the disease causing mutation in BRCA1

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28
Q

Splicing

A

The noncoding (introns) are removed from the main transcript= mature mRNA

Cuts after before GT of the intron until after the AG end of the intron

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29
Q

What happens when a splice site is disrupted?

A

Exon can be skipped
It’s almost impossible to predict what might happen

Intron might not get spliced out= keep going until the next one is found= extra DNA sequence

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30
Q

Small duplications/deletions

A
  • 1 or more nucleotides can be inserted/deleted/ both
  • if the number of bases are not multiples of 3= then there’s a shift of the codon reading frame (frameshift mutation) = Nager Syndrome
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31
Q

Large duplication/deletions

A
  • 1 or more exons are duplicated (rare) or deleted
  • most common is x-linked duchenne muscular dystrophy (70% of patients have a duplication/deletion of the DMD gene)

.33 of patients have a de novo mutation (not found in the mom)

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32
Q

Autosomal dominant

A

All generations are affected but not all affected have an affected parent; maybe low penetrance?

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33
Q

Autosomal recessive

A

All parents would have have to be carriers; would have to have a very high carrier frequency for 3 members of the family to each marry a carrier

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34
Q

X-linked dominant

A

Not all affected have an affected parent; low penetrance

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35
Q

X-linked recessive

A

Unaffected father with affected grandsons; affected female

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36
Q

Dynamic mutations repeat expansions give an example

A

Fragile X syndrome- caused by repeated (CGG)n near the promoter of the FMR1 gene

Normal= 6-54

Permutation=55-200

Full mutation= 200- 1000

Permutation carrier female= affected offspring
Permutation carrier male= permutation carrier offspring and affected grandsons from his daughter
Risk of expansion depends on the size of the permutation

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37
Q

Dynamic mutations

A

A major cause of neurological disorders
Expansion of a simple repeat in coding region or noncoding region

Usually demonstrate reduced penetrance alleles and variable expressivity

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38
Q

Consequences of mutation

A

Loss of function= Fragile X
Friedreich Ataxia

Gain of function= Huntington (coding), Myotonic Dystrophy

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39
Q

Anticipation

A

Earlier onset
Size of the expansion proportional to age of onset
Bigger the expansion the more unstable it becomes for the next generation and earlier age of onset

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40
Q

Myotonic Dystrophy Type1

A

CTG repeat in the 3’ UTR of the DMPK gene

Mild 50-150: cataract, mild myotonia
Classic 100-1000: muscle weakness and wasting, myotonia, cataract, cardiac conduction abnormalities
Congenital: >1000 hypotonia/severe generalized weakness at birth, respiratory insufficiency (early death)

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41
Q

Anticipation through maternal inheritance

A

Myotonic dystrophy

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42
Q

Anticipation inheritance

A

Huntington’s

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44
Q

Outcomes of the post HGP era

What do each of is carry

A

76-190 rare non-synonymous changes that are predicted to be deleterious

<20 loss of function and known disease-associated mutations

40-80 SNPs that are not present in our parents (new seq changes)

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45
Q
A
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46
Q

Variant Nomenclature
cDNA (RNA) level

duplication
insertion
protein level

A

all numbering is in relation to the A in ATG (start codon) increases from there on

  • duplication: 1 or more extra bases are present that are identical to those preceding it
    insertion: 1 or more extra bases prsants that DO NOT match this preceding it
  • protein level- all AA are numbered starting from MET
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47
Q

Loss of Function Mutations

A

protein function is lost or reduced in the cell

  • can result from missense, splicing, frameshift, or large deletion/duplication
  • usually recessive mutations (both copies are mutated)

Cystic fibrosis- loss of function mutations in the CFTR gene

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48
Q

Gain of function mutations

A
  • mutations that enhance normal protein function
  • usually dominant disorders

ex) Achondroplasia–> single nonsynomous protein
- binds all the time doesn’t let the bones grow
- FGFR3

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49
Q

Novel Function

A

-proteins gain a new function or property

Sickle cell anemia:
RBC become sickled when deoxygenated and eventually stay sickled

-organ damage(liver) anemia and recurrent infections

also Huntington’s disease: presence of an expansion gives the genes new function–> neurone slowly killed

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50
Q

Dominant Negative Mutations

A
  • a mutation that results in a protein that adversely affects the normal product within the same cell
    ie) Osteogenesis perfecta (nonsense frameshift ) –> having abnormal collagen is worse than no collagen at all
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51
Q

Heterochronic/Ectopic expression

A
  • gene is expressed at the wrong time (heterochronic) or in the wrong place ectopic–> often dominant disorders
  • deletion in the beta-globin locus for fetal hemoglobin–> where the gene isn’t turned off when it should be
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52
Q

haploinsufficiency

A
  • individual that is heterozygous for a certain gene is clinically affected because 1 gene is not enough for normal function
  • if mutation is from normal parents= its a de novo mutation
  • inherited as dominant disorders, with variable expressivitiy (can be inherited or de novo)
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53
Q

Gene dosage

A
  • extra copies of normal gene products are sufficient to cause disease
  • inherited as dominant disorders
  • may have variable penetrance and expressivity

ie) Charcot-Marie-Tooth Disease Type 1A
- extra copy of the PMP22 gene where the loss can also cause disease

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54
Q

Mendels law of segregation

A

-every individual has 2 alleles for each trait–> one will be randomly passed on to offspring

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55
Q

Mendel’s Law of independent assortment

A

-separate genes for separate traits are passed independently to offspring

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56
Q

gene linkage

A

certain genes usually inherited together, because they are on the same chromosome. Thus parental combinations of characters are found more frequently in offspring than non parental. (parental vs recombination)

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57
Q

genetic marker

A

A gene or (a fragment of) DNA sequence having a known location on a chromosome, has an easily identifiable phenotype and whose inheritance pattern can be followed.

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58
Q

allele

A

one of the alternate versions of a DNA sequence at a given marker

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59
Q

law of independent assortment

  • linked
  • unlinked
A

linked: one allele from Parent 1 is associated with one allele from Parent 2 >50%

unlinked:
disease state will be found equally associated with both marker alleles

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60
Q

Genetic Maps

A
  • distance between markers is the recombination rate (theta)
  • where 1% recombination= 1cM
  • framework for linkage mapping
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61
Q

LOD formula

A

log10 x (prob of birth seq with a given linkage value/ prob of birth sequence with no linkage) = log10 (1-0)^NR x0^R )/(0.5 ^(NR+R) 0=THETHA

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62
Q

LOD SCORE

A
  • stat test used for linkage analysis
  • in order to find out if the two loci are actually linked or the data was linked totally by chance
  • positive= linkage (greater than 3)
  • negative= no linkage
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63
Q

uses of genetic linkage

A
  • used by clinics before DNA sequencing was available to determine risk of being carrier, affected etc
  • positional cloning: identify the genomic location of a disease gene without any prior knowledge on where or what the causative gene is.
  • both are family context-dependent
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64
Q
A
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65
Q

What is cancer?

A

Clonal multistep process of the genes involved in growth

-uncontrolled growth

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66
Q

Neoplasia

A

New growth

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67
Q

Hyperplasia

A

Too much growth

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68
Q

Dysphasia

A

Incorrect growth

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69
Q

Benign

A

Localized growth

70
Q

Malignant

A

Capable of growth

71
Q

Metastasis

A

Distant growth

72
Q

Cancer is a multistep process

A

Not always a mutations; can be caused due to a gain or loss of genes; every cancer is different with different genes involved

-accumulation of genetic errors in genes that control growth

First step can be inherited=cancer in families (some can be DNA repair genes)

73
Q

Inheritance of Retinoblastoma

A

Eye tumor in childhood but not always

Sporadic inheritance: just have one individual no one else in the family has it

Familial inheritance: in every generation or skips generations

74
Q

Mendelian

A

5% inherited
-in the germline is inherited; lets say you visit some place you increase the chances of having a somatic mutation–> earlier onset

affected individuals in every generation of a pedigree (can skip generations as well)

75
Q

Sporadic

A

95% sporadic
-waiting for random exposures to knock out genes=cancer

dying old old age= accumulation of mutations over time

only 1 person affected in a pedigree

76
Q

Familial Adenomatous Polyposis

A
  • multiple polyps (colon cancer in young adults)
  • inherited mutation in gene that regulates cell division in colon
  • APC gene mutation
  • Mendelian
77
Q

Li Fraumeni Pedigree

A
  • multiple types of cancers
  • mendelian
  • mutation in a gene that regulates cell replication in multiple cell types

TP53 gene mutation
**if theres a legend=autosomal dominant

78
Q

Knudson’s 2 Hit Hypothesis

A

1st hit= inherited

2nd hit= acquired

79
Q

Inherited Cancer Predisposition

-inheritance of genetic alteration, normal phenotypes at birth

A

RB1 retinoblastoma

APC- Familial Adenomatous Polyposis

TP53-> Li Fraumeni pedigree

80
Q

inheritance of genetic alteration, part of a recognizable syndrome

A

Down Syndrome

81
Q

Chomosome instability syndromes

A

chromosomes are broken because DNA repair mechanisms dont work, therefore accumulating errors

(basically mutation in genes responsible for DNA repair

Faconi Anemia
Bloom Syndrome
Ataxia telangiectasia
Xerderma pigmentosum

82
Q

Down Syndrome

A

-trisomy 21–> tongue is out because mouth is too small; gap btw big toes and the rest of the toes;

High risk of transient myelodyplastic syndrome at birth (cells dont look right; sometimes can b acute; individual gets older quicker (avg age 32)

10-100 fold risk of acute megakaryoblastic leukemia –> leukemia that affects platelattes in the blood

83
Q

Fanconi Anemia

A

growth retardation (thumb sticking out)
thumb anomalies
increased risk of of leukemia and liver cancer
chemical induced chromosome breakage –> unrepairable
defect in DNA repair enzyme

84
Q

Bloom Syndrome

A
  • facial butterfly rash
  • more in the Jewish
  • increased risk of leukemia
  • increased sister chromatid exchange –> Harlarlequin banding)

mutation in BLM gene–> 1 chromosome completely light other one completely dark; normal you might have one maybe 2–> these individuals have many of these chromosomes

DNA unwinding enzyme:
-cant correct; cnat make the the DNA into RNA -> protein

85
Q

Ataxia Telangiectasia

A
  • occular telangectasias (corner of eyes have fine blood vessels)
  • loss of muscle control (not being able to control walking
  • lymphoid mailignancies (will not take body xrays etc)

mutation in the ATM gene
DNA repair enzyme

86
Q

Xeroderma Pigmentosum

A

extreme sun sensitivity
blistering and skin cancer
mutation in UV dimer repair enzyme

87
Q

Environmental Causes of cancer progression? LIST

A 
radiation 
chemicals
 viruses 
diet 
lifestyle
88
Q

radiation

A
  • UV light from the SUN= melanoma–> cancer of the pigment in skin (depth not size that matters)
  • ioniaing radiation in an atomic bomb= Leukemia
  • previouslt X-rays caused lung cancer
89
Q

Chemicals

A

asbestos–> lung cancer

smoke soot (small boys used to clean chimneys) scrotal cancer

fertilizers, pesticides= plasma cell neoplasms

90
Q

Viral

A

Hepatitis–> liver cancer
EBV–> Burkitt’s lumphoma and others
HPV-> cervical cancer
HIV–> primary effusion lymphoma and others

91
Q

Lifestyle

A

smoking= lung cancer
prostitutes: cervical cancer
nuns= breast cancer because nit getting pregnant etc

92
Q

diet

A

nitriles in preservatives= liver cancer

  • alcohol= liver cancer
  • lack of fibre–> colon cancer
93
Q

Japanese graph

A

stomach cancer is higher in the Japanese compared to the California caucasians whereas prostate cancer is higher in the the California Caucasians than the Japanese

94
Q

Cancer is a Genetic Process

A
  • accumulation of defects in genes involved in cell replication and cell death
  • grouped by function
95
Q

Cell replication Life cycle

A

1) oncogenes= green light
2) grows
3) splits into 2 cell
4) TSG gatekeeper genes= STOP
5) cell is repaired (TSG) caretaker genes
6) and the cycle starts again

96
Q

Tumor suppressor genes

LIST GATEKEEPERS AND CARETAKERS

A

GATEKEEPERS
-RB1 and TP53 both are cell cycle regulators

CARETAKERS

  • BRCA1 (repair DNA double)
  • BRCA2( strand breaks)
  • MLH1(repair DNA mucleotide)
  • MSH2(mismatch)
97
Q

Gatekeeper TSG: RB1

A

-eye tumour caused by hits in each of the 2 copies of the RB1 gene that suppresses cell growth within the eye

Familial: 1st hit inherited 
2nd acquired (mendelian)

Sporadic: both hits are acquired

98
Q

La Fraumeni pedigree

A

TP53 gene mutation
tumor supressor gene
gatekeeper of cell cycle
multiple cell types

99
Q

Gatekeeper TSG: TP53

A
  • checks DNA for damaged prior to making a copy of it
  • if the checkpoint is non-functional
  • leads to accumulations of mutations
  • affects many cell types

DNA damage (radiation)–> cell cycle is arrested–> irreplaceable damage–> APOPTOSIS (elimination of damaged and a potentially cancerous cells)

OR

DNA damage (radiation)–> cell cycle arrest–> DNA repair

100
Q

Caretaker TSG: MLH1 & MSH2

A
  • repairs DNA replication mistakes (spell check)
  • non-function leads to accumulation of genetic mutations
  • inheritance of the MLH1 & MSH2 mutations
  • hereditary Colon cancer (Non-Polyposis type)
101
Q

Function of Cancer genes

A

oncogenes–>TSG’S

1) Gatekeeper–>AD
2) Caretaker–> AD and AR

=chromosome instability syndromes

102
Q

Function of Oncogenes

A
  • genes involved in cell proliferation
  • WT= c-onc (cell oncogene)
  • carcinogenic when upregulated
  • mutated type= onc
103
Q

What year did the first association of a chromosome rearrangement with cancer?

-example

A

-Chronic Myeloid leukemia caused by the philadelphia chromosome (extremely tiny)

1960

104
Q

what year was the human chromosome G-banded

A

1970s

105
Q

Chromosome Rearrangements

A

a) inversion
b) insertion
c) translocation

106
Q

inversion

A
  • chromosomal rearrangement
  • chromosome is reversed from end to end

centromere included= pericentric

not= paracentric

107
Q

insertion

A

-DNA segment from 1 chromosome is inserted into another chromosome

108
Q

translocation

A
  • transfer a segment of one chromosome to another chromosome
  • if 2 nonhomo chromosomes exchange parts that the transloaction in reciprocal
109
Q

Robertsonian translocation

A

translocation btw 2 acrocentric chromosomes by fusion at or near the centromere, with the loss of the short arms

110
Q

FISH

A

1990s

-denature–> hybridize with a fluorescent probe–> visualize

111
Q

Gene Fusion found by FISH

Philadelphia Chromosome Rearrangement

A 
------------ ABL 9 gene
//////////// 22BCR gene

———///// ABL/BCR gene t(9;22)

-precise rearrangement= creates a fusion gene and a fusion protein

ABL1= oncogene 
BCR= breakpoint cluster region
112
Q

Fusion Protein Targetted Therapy

A

ABL1-BCR gene fusion responds to tyrosine kinase inhibitors

-drug is specially made to inhibit the ABL1-BCR fusion protein (CML/AML/ALL)

113
Q

2008 WHO Classification

A
  • WHO classifications of tumours are based on the primary genetic rearrangements
  • dont need to know what it is to remove it, but do need to know what it is to treat it
114
Q

Genes in Cancer Diagnosis: Fatty tumors

A
  • chromosomes 3; 12
  • lipoma
  • atypical lipomatous tissue/well differentiated lipoma or dedifferentiated lipoma
  • myxoid liposarcoma
115
Q

Genes in prognosis: neuroblastoma

A
  • neuroblastoma
  • childhood solid tumour
  • in nervous system
  • outside of the brain
116
Q

ALK FISH predicts Crizotinib Response

A
  • NSCLC: non-small cell adenocarcinoma of the lung
  • ALK FISH rearrangements in 3-5%
  • Crizotinib significantly reduces tumor burden
117
Q

ALK ATP binding pocket –> ALK in Personalized Medicine

A

Crizotinib aka XALKORI

Phase 2: 79/82 substantial reduction in tumor burden

Phase 3: FDA approval in 36 months

118
Q

Alberta Thoracic Oncology Program

A

EGFR mutation positive:–> Erlotinib/Gefitinib

ALK rearrangement positive: crizotinib

119
Q
A
120
Q

Genetics

A

the study of hereditary and the variation of inherited characteristics

121
Q

Epigenetic

A

-heritable changes in gene expression not caused by changes in DNA sequence

122
Q

Waddinton’s Epigenetic Landscape

A

the epigenome tells the cell what to be

123
Q

Molecular mechanics that mediate epigenetic

A

RNA/histone modification/ DNA methylation all cause Chromatin (euchromatin or heterochromatin) remodelling/heritable gene expression

*gene expression of daughter cells is the same as the mother cell

124
Q

epigenetic phenomenon

A
  • x-chromosome inactivation
  • genomic imprinting
  • centromere/telomere function

etc

125
Q

euchromatin

A

-active
-gene rich regions
transcription occurs
-less condensed

126
Q

interphase chromatin

A
  • highly condensed
  • gene poor
  • found in transcriptionally inert regions
127
Q

chromatin’s role with histones

A

DNA wraps around the histone twice and nucleosomes compact it

128
Q

what are the basic building blocks of Chromatin

A

histones
-dimers form tetramer which form histone octamer (DNA of tetramers wrap around twice)

-the histone tails interact with DNA and these tails serve as the basis for the epigenetic marks

129
Q

Post translational modifications of histone tails

A
  • phosphorylation
  • ubiquitination
  • acetylation
  • methylation
130
Q

Features of Histone Modifications

A
  • covalently attached groups to histone tails
  • methyl
  • acetyl
  • phospho
  • ubiquitin
  • reversibile and dynamic
  • directs transcriptional signals -> DNA is negatively charged and histone tail is positively charged–> if you take aways the positive charge= they will no longer interact anymore
131
Q

Histone modifiers

A

a) Writing
acetylases/methylases/phosphorylases (add groups)

b) Erasing
deacetylases, demethylases/ phosphatases
-epigenetic marks need to be erased for genes to be expressed

c) Reading= chromatin remodelling factors
- interpret the marks (remodel the chromosome)

132
Q

Chromatin and Nucleosomes

A

nucleosome moves or is physically removed by the chromatin remodelling to gain or inhibit access to the promoter–> can also condense or add nucleosomes

-nucleosome spacing/mobility/ assembly

133
Q

histone acetylation is associated with gene activation

A 
inactive= no acetyl groups 
active= acetyl groups attached
  • transcription factors tell DNA to open (acetylate)
  • you cant change DNA but you can change the acetyl marks
134
Q

ChIP

A

Techniques to study Histone Modifications

-Chromatin immunoprecipitation: Strategy for localizing histone marks

135
Q

ChIP-qPCR

A

if you know the target gene

136
Q

ChIP-seq

A

or other genome-wide techniques: unbiased

137
Q

limitations of ChIP

A

a) antibody specificity: need 1 that corresponds to what you are looking for
b) inherent biases of localization methods

138
Q

techniques to study histone modifications

A
  • take DNA and crosslink then fragment and then put an antibody in it and the protein of interest and DNA attached will bind to the antibody
  • remove the proteins and you are left with the DNA you need. do massive sequencing of your DNA the more DNA your antibody pulls down, the more you sequence
139
Q

ChIP vocab

  • depth
  • coverage
A
  • the number of mapped sequence tags

- how much of the genome the reads can be mapped to

140
Q

if a gene is turned on, why would you have repressive marks?

A

-to prevent criptic transcription (noncoding RNA) or to repress isoforms (can alter gene function)

141
Q

inactive genes are full of

A

repressive marks

142
Q

the histone code hypothesis

A
  • you can predict if a gene is on or off, but its more complex
  • there are many different factors that influence the genome
143
Q

Histone cross talk

A

basically DNA methylation will try to turn off transcription and another might try to turn it on (interference with each other)

144
Q

DNA methylation

A
  • chemical modification of DNA

- can be inherited without a sequence change

145
Q

methylation most frequent at

A

5’CpG 3’ dinucleotides

146
Q

CpG islands

A

(methylation(

-regions of high CG content 60% of mammal promoters found here

147
Q

DNA hypermethylation=

A

associated with gene silencing

148
Q

promoter unmethylated

A

genes can be transcribed

149
Q

promoter methylated

A

gene is silenced

150
Q

methylated binding proteins recognize CpG island promoters then

A

either methylation or histone modification causes methylation to occur

151
Q

x chromosome inactivation

A

males: y chromosome lost a lot of ancestral genes
females: silence most genes on 1 x-chromosome

152
Q

barr body

A

x-inactivation proof
-properties of X inactivation (late replication in the S phase)

-remains condensed in interphase

153
Q

XIST

A
  • interacts with proteins which interact with histones and methylation of histones of soon to be inactive x happens
  • once x is inactive, it can’t become active
154
Q

genomic imprinting

A

zone you inherited something from
-genes that are not turned on are methylated

-differential expression of genes depending on the parent-of-origin

155
Q

disorders of genomic imprinting (2)

A

Prader-willi Syndrome (dad) and Angelman Syndrome (mom)

-both are caused by the same deletion= determined which parent they inherit it from

156
Q

epigenetics and cancer

A
  • you can’t change the genome and cancer occurs in the genome
  • all cancers start with DNA (usually a mutation)
  • then a gene is shut off and this causes changes within a cell
  • stem cell looks like a cancer cell in the epigenetic level
157
Q

treatment of cancer by modifying the epigenome

A
  • mechanism of action
  • direct incorp into DNA
  • blocks effects of DNA methyltransferase
  • causing hypomethylation of DNA
  • reverses inactivations of tumor suppressor genes
  • can lead to cytotoxicity

cytosine analog–> insert DNA into the helix therefore unmethylated cytosine, now tumor expression (or w/e gene) turns on

158
Q

ENCODE what it stands for?

A

ENCyclopedia Of Dna Elements

159
Q

obj of ENCODE

A

find all functional elements

  • bound by specific proteins
  • -histone modifications/DNA mthylation/transcribed(epigenetic features)
160
Q

ENCODE use obj too

A 
genes (coding and noncoding) 
promoters 
enhancers (activation/silencing) 
specific transcription factor binding sites 
insulators 
chromatin states
161
Q

ENCODE methods

RNA-Seq

A

different fractions of RNA–> sequencing

162
Q

ENCODE methods

ChIP-seq

A

chromatin immunoprecipitation- DNA binding protein–> seq

163
Q

ENCODE methods

DNase-seq

A

nucleosome- depleted DNA–> seq

164
Q

ENCODE methods

RRBS

A

bisulphite treatment–> unmethylated C—->U–> seq

165
Q

ENCODE methods 3C,5C

A

chromatin interactions–> sequencing

5C=Carbon Copy Chromosome Conformation Capture

  • crosslinking
  • digestion
  • ligation
166
Q

80.4% of human genome linked to

A

biochemical functions–> bound by a transcription factor

  • transcribed
  • modified histone
167
Q

syndrome

A

bunch of clinical features that are observed in, characteristic of a single condition

168
Q

Rett Syndrome

A
  • neurodevelopemtn disorder
  • mostly females affected
  • normal growth and development followed by a slowing down of development
  • main effect= loss of motor and intellectual abilities
  • microcephaly, seizures, stereotypical hand movements

caused by mutations in the MeCP2 protein

169
Q

CHARGE Syndrome

A 
colobomas of eyes 
heart defects 
atresia of choanae 
retardation of growth/developemnnt 
genital hypoplasia 
geneital hypoplasia 
ears

CHD7 protein mutations

170
Q

Rubinstein-Taybi Syndrome

A 
broad thumbs and toes 
short 
facial features 
low set ears 
ocular abnormaliteis 
cardiac abnomalities 
ID carying

CREBPP/P300- Histone acetyltransferase

171
Q

intellectual disability

A

big feature of diseases linked to mutations in chromatin proteins

  • brain functions depends on the interactive actions of many genes
  • sensitive to mass gene expression as well

CMMB Midterm 1 (6 decks)

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