NR 507 Advanced Pathophysiology Midterm Exam Study Guide
I I I I I I I
Epigenetics
1. Defects Iin Ithe Iencoding Iof Ihistone-modifying Iproteins I(Chp I6 Iand I12 Iwk I1)
Histone Imodification I(e.g., Ihistone Iacetylation Iand Ideacetylation, Ialterations Iin Ichromatin): IChromatin Icompaction
Iand Iorganization Ihelp Ito Iregulate Igene Iexpression, Idetermining Iand Imaintaining Icell Iidentity. IChromatin Istructure
Imust Ibe Icontrolled Iin Iself-renewing Iand Idifferentiated Icells Iin Icell Irenewal Isystems. IFor Iexample, Ithere Iare
Idifferences Iin Ichromatin Istructure Iin Istem Icells Iand Iterminally Idifferentiated Icells
✓ are Ichemical Imodifications Iof IDNA Isequences Ithat Ialter Ithe Iexpression Iof Igenes, Iresulting Iin Idisease Iand
Iphenotypical Ivariations I(upon Igenetics)
✓ types Iof Iepigenetic Imodifications
✓ > IDNA Imodification
> histone Imodification
> Microribonucleic Iacids I(miRNAs) Ior Imature ImiRNAs
> specific Ienvironmental Ior Inon-genetic Ifactors, Isuch Ias Idiet Iand Iexposure Ito Icertain Ichemicals Ican Iaffect
Iepigenetic
✓ Histone Imodifications- Iin Idiverse Ibiological Iprocesses Isuch Ias Itranscriptional Iactivation/inactivation,
chromosome Ipackaging, Iand IDNA Idamage/repair.
✓ Histone Imodifications I(e.g. Ihistone Iacetylation Iand Ideacetylation, Ichromatin Ialterations)- IChromatin
Icompaction Iand Iorganization Ihelp Ito Iregulate Igene Iexpression, Idetermining Iand Imaintaining Icell Iidentity
✓ quantitative Idetection Iof Ivarious Ihistone Imodifications- Iwould Iprovide Iuseful Iinformation Ifor Ia Ibetter
understanding Iof Iepigenetic Iregulation Iof Icellular Iprocesses Iand Ithe Idevelopment Iof Ihistone Imodifying
Ienzyme-targeted Idrugs.
✓ Histone IModification- IResults:
> Histone Iacetylation Iand Ideacetylation
> alterations Iin Ichromatin
2. Epigenetics Iand I(45) Iits Irole Ion Ihuman Idevelopment. I(chp I6)
✓ the Istudy Iof Iinfluences Ion Igene Iexpression Ithat Ioccur Iwithout Ia IDNA Ichange.
✓ diseases Iand Iother Iphenotypic Ivariation Iare Icaused Iby Imechanisms Iother Ithan Ichanges Iin Ithe IDNA
1
Isequences—termed Iepigenetics I(“upon Igenetics”). Epigenetics Iis Ithe Istudy Iof Iheritable Ichanges Iin Igene
Iexpression Ior Iphenotype Icaused Iby Imechanisms Iother Ithan Ichanges Iin IDNA Isequences. IEpigenetic
Imodifications Ican Icause Iindividuals Iwith Ithe Isame IDNA Isequences I(such Ias Iidentical Itwins) Ito Ihave
Idifferent Idisease Iprofiles
3. Totipotent Icells
✓ the Izygote Iand Iearly Iembryonic Icells
✓ Totipotent Istem Icells Imean Ithat Ithey Ican Iproduce Ian Ientire Iorganism Ilike Ifertilized Ioocyte
✓ What Iare Itotipotent Istem Icell
✓ They Iare Istem Icell Ithat Ican Igive Irise Ito Iany Iand Iall Icell Iof Ithe Ihuman Ibody.
IThey Ican Igive Irise Ito Ia Ientire Iorganism.
They Icells Iare Ifound Ion Ithe Ifirst Iround Iof Ireplication Iwhen Ithe Isperm Iand Iegg Iunite Ior Iat Ithe Ivery Iearliest
Istage Iof Idevelopment++.
and I(49) Iits Iability Ito Idifferentiate Iinto Iany Itype Iof Icell
50. IPrader-Willi Isyndrome Iand I– Imissing Ithe IPATERNALLY Iimprinted Icopy Iof Ichromosome I15,
✓ Prader-Willi Isyndrome-features Iinclude Ishort Istature, Ihypotonia, Ismall Ihands Iand Ifeet, Iobesity, Imild Ito
Imoderate Imental Iretardation, Iand Ihypogonadism
✓ behavioral Icharacteristics Iof Iprader Iwilli
Temper Itantrums
IStubbornness
1
, Controlling/manipulativ
I
e
Compulsivity I(especially Iwith Ifood)
✓ Difficulty Iwith Ichanges Iin Iroutine
✓ 10-20% Iyoung Iadults Idevelop Ipsychosis
✓
4. Angelman Isyndrome? I– Iloss Iof Ithe Imaternal Icopy Iof IUBE3A
✓ 2 Imajor Icauses Iof Iangelman
microdeletion
Ipaternal IUPD
phenotype Iof Iangelman Isyndrome
Isevere Idevelopmental
IdelayINO ISPEECH
"happy Ipuppet"
Ihyperactivity
major Iseizure Iproblem
Ifascinated Iwith Iwater
✓ Angelman Isyndrome- Isame I4-Mb Ideletion, Iinherited Ifrom Ithe Imother, Icauses IAngelman Isyndrome, Iwhich Iis
characterized Iby Isevere Imental Iretardation, Iseizures, Iand Ian Iataxic Igait.
✓ Deletions Iin IPrader-Willi Iand IAngelman ISyndromes Iare Iidentical Iand Iindistinguishable Iat Ithe IDNA Ilevel.
✓ Gene Iresponsible Ifor IAnglemman Isyndrome Iencodes Ia Iligase- Iinvolved Iin Iprotein Idegradation Iduring Ibrain
Idevelopment.
This Igene Iis Ionly Iactive Ion Ithe Ichromosome Icopy Iinherited Ifrom Ithe Imother.
✓ A Imaternally Itransmitted Ideletion Iremoves- Ithe Ionly Iactive Icopies Iof Ithese IAngelman ISyndrome Igenes,
Iproducing Ithe Ifeatures Iof IPrader IWilli Isyndrome.
Cellular IProliferation
5. 5-Azacytidine Iand Ithe(44) Itreatment Iof Icancer I(Chap I6 I& IChp I12- Iwk I1)
✓ What Idoes I5-azaC Ido Ito IDcm? IInhibits IDcm. IDcm Ibecomes Icovalently Itrapped Ito IDNA I& Idegraded
✓ What Iwere Ithe I3 Ieffects Iof I5-azaC Itested?
1. On IDNA Imethylation
2. Bacterial Igrowth
3. Site Ispecific Imethylation
4. On Itranscriptome Ichanges
✓ If I"aza" Iis Iadded Ito IE.Coli Iin Iincreasing Iconcentrations, Iwhat Ihappens? IUn-methylated IDNA Iwill Iincrease
Iproportionally I(Since IDcm Iis Iinhibited)
✓ How Idoes Ihigh Iconc. Iof IAza Iaffect Ibacterial Igrowth? IHigh Iconc. Iof IAza Iinhibits Ibacterial Igrowth I(after I2
hours)
✓ a Idemethylating Iagent, Ihas Ibeen Iused Ias Ia Itherapeutic Idrug Iin Ithe Itreatment Iof Ileukemia Iand
Imyelodysplastic Isyndrome
✓ 5-azacytidine I(which Ireverses Ithe Ieffects Iof IDNA Imethyltransferases I[DNMTs]), Ihave Iproven Ieffective Iin
reactivating Isilenced Itumor-suppressor Igenes Iin Ithe Itreatment Iof Iselected IcancersI6.
Ithe Irole Iof Iinactive IMLH1 Iin Ithe Idevelopment Iof Isome Iforms Iof Iinherited Icolon Icancer.
✓ A Imajor Icause Iof Ione Iform Iof Iinherited Icolon Icancer I(hereditary Inonpolyposis Icolorectal Icancer I[HNPCC]) Iis Ithe
Imethylation Iof Ithe Ipromoter Iregion Iof Ia Igene, IMLH1, Iwhose Iprotein Iproduct Irepairs Idamaged IDNA. IWhen
IMLH1 Ibecomes Iinactive, IDNA Idamage Iaccumulates, Ieventually Iresulting Iin Icolon Itumors.
7. Effects Iof Iethanol Ion Ineural Istem Icells Iability Ito Idifferentiate Iinto Ifunctional Ineurons I(chap I13,wk I1) I(Chap I2
✓ The Imolecular Iactions Iof Iethanol Iare Ibelieved Ito Iinclude Isite-specific Ichanges Ito Ihistone Imodifications Iand
Ialterations Iof Ione-carbon Imetabolism Icausing Imethylation Ichanges.
✓ MicroRNA Iexpression Ihas Irecently Ibeen Ilinked Ito Ialcohol Iconsumption Iin Ia Icase-control Istudy Iof Ihead Iand
neck Icancer I(i.e., Ihead Iand Ineck Isquamous Icell Icarcinoma
✓
2
I I I I I I I
Epigenetics
1. Defects Iin Ithe Iencoding Iof Ihistone-modifying Iproteins I(Chp I6 Iand I12 Iwk I1)
Histone Imodification I(e.g., Ihistone Iacetylation Iand Ideacetylation, Ialterations Iin Ichromatin): IChromatin Icompaction
Iand Iorganization Ihelp Ito Iregulate Igene Iexpression, Idetermining Iand Imaintaining Icell Iidentity. IChromatin Istructure
Imust Ibe Icontrolled Iin Iself-renewing Iand Idifferentiated Icells Iin Icell Irenewal Isystems. IFor Iexample, Ithere Iare
Idifferences Iin Ichromatin Istructure Iin Istem Icells Iand Iterminally Idifferentiated Icells
✓ are Ichemical Imodifications Iof IDNA Isequences Ithat Ialter Ithe Iexpression Iof Igenes, Iresulting Iin Idisease Iand
Iphenotypical Ivariations I(upon Igenetics)
✓ types Iof Iepigenetic Imodifications
✓ > IDNA Imodification
> histone Imodification
> Microribonucleic Iacids I(miRNAs) Ior Imature ImiRNAs
> specific Ienvironmental Ior Inon-genetic Ifactors, Isuch Ias Idiet Iand Iexposure Ito Icertain Ichemicals Ican Iaffect
Iepigenetic
✓ Histone Imodifications- Iin Idiverse Ibiological Iprocesses Isuch Ias Itranscriptional Iactivation/inactivation,
chromosome Ipackaging, Iand IDNA Idamage/repair.
✓ Histone Imodifications I(e.g. Ihistone Iacetylation Iand Ideacetylation, Ichromatin Ialterations)- IChromatin
Icompaction Iand Iorganization Ihelp Ito Iregulate Igene Iexpression, Idetermining Iand Imaintaining Icell Iidentity
✓ quantitative Idetection Iof Ivarious Ihistone Imodifications- Iwould Iprovide Iuseful Iinformation Ifor Ia Ibetter
understanding Iof Iepigenetic Iregulation Iof Icellular Iprocesses Iand Ithe Idevelopment Iof Ihistone Imodifying
Ienzyme-targeted Idrugs.
✓ Histone IModification- IResults:
> Histone Iacetylation Iand Ideacetylation
> alterations Iin Ichromatin
2. Epigenetics Iand I(45) Iits Irole Ion Ihuman Idevelopment. I(chp I6)
✓ the Istudy Iof Iinfluences Ion Igene Iexpression Ithat Ioccur Iwithout Ia IDNA Ichange.
✓ diseases Iand Iother Iphenotypic Ivariation Iare Icaused Iby Imechanisms Iother Ithan Ichanges Iin Ithe IDNA
1
Isequences—termed Iepigenetics I(“upon Igenetics”). Epigenetics Iis Ithe Istudy Iof Iheritable Ichanges Iin Igene
Iexpression Ior Iphenotype Icaused Iby Imechanisms Iother Ithan Ichanges Iin IDNA Isequences. IEpigenetic
Imodifications Ican Icause Iindividuals Iwith Ithe Isame IDNA Isequences I(such Ias Iidentical Itwins) Ito Ihave
Idifferent Idisease Iprofiles
3. Totipotent Icells
✓ the Izygote Iand Iearly Iembryonic Icells
✓ Totipotent Istem Icells Imean Ithat Ithey Ican Iproduce Ian Ientire Iorganism Ilike Ifertilized Ioocyte
✓ What Iare Itotipotent Istem Icell
✓ They Iare Istem Icell Ithat Ican Igive Irise Ito Iany Iand Iall Icell Iof Ithe Ihuman Ibody.
IThey Ican Igive Irise Ito Ia Ientire Iorganism.
They Icells Iare Ifound Ion Ithe Ifirst Iround Iof Ireplication Iwhen Ithe Isperm Iand Iegg Iunite Ior Iat Ithe Ivery Iearliest
Istage Iof Idevelopment++.
and I(49) Iits Iability Ito Idifferentiate Iinto Iany Itype Iof Icell
50. IPrader-Willi Isyndrome Iand I– Imissing Ithe IPATERNALLY Iimprinted Icopy Iof Ichromosome I15,
✓ Prader-Willi Isyndrome-features Iinclude Ishort Istature, Ihypotonia, Ismall Ihands Iand Ifeet, Iobesity, Imild Ito
Imoderate Imental Iretardation, Iand Ihypogonadism
✓ behavioral Icharacteristics Iof Iprader Iwilli
Temper Itantrums
IStubbornness
1
, Controlling/manipulativ
I
e
Compulsivity I(especially Iwith Ifood)
✓ Difficulty Iwith Ichanges Iin Iroutine
✓ 10-20% Iyoung Iadults Idevelop Ipsychosis
✓
4. Angelman Isyndrome? I– Iloss Iof Ithe Imaternal Icopy Iof IUBE3A
✓ 2 Imajor Icauses Iof Iangelman
microdeletion
Ipaternal IUPD
phenotype Iof Iangelman Isyndrome
Isevere Idevelopmental
IdelayINO ISPEECH
"happy Ipuppet"
Ihyperactivity
major Iseizure Iproblem
Ifascinated Iwith Iwater
✓ Angelman Isyndrome- Isame I4-Mb Ideletion, Iinherited Ifrom Ithe Imother, Icauses IAngelman Isyndrome, Iwhich Iis
characterized Iby Isevere Imental Iretardation, Iseizures, Iand Ian Iataxic Igait.
✓ Deletions Iin IPrader-Willi Iand IAngelman ISyndromes Iare Iidentical Iand Iindistinguishable Iat Ithe IDNA Ilevel.
✓ Gene Iresponsible Ifor IAnglemman Isyndrome Iencodes Ia Iligase- Iinvolved Iin Iprotein Idegradation Iduring Ibrain
Idevelopment.
This Igene Iis Ionly Iactive Ion Ithe Ichromosome Icopy Iinherited Ifrom Ithe Imother.
✓ A Imaternally Itransmitted Ideletion Iremoves- Ithe Ionly Iactive Icopies Iof Ithese IAngelman ISyndrome Igenes,
Iproducing Ithe Ifeatures Iof IPrader IWilli Isyndrome.
Cellular IProliferation
5. 5-Azacytidine Iand Ithe(44) Itreatment Iof Icancer I(Chap I6 I& IChp I12- Iwk I1)
✓ What Idoes I5-azaC Ido Ito IDcm? IInhibits IDcm. IDcm Ibecomes Icovalently Itrapped Ito IDNA I& Idegraded
✓ What Iwere Ithe I3 Ieffects Iof I5-azaC Itested?
1. On IDNA Imethylation
2. Bacterial Igrowth
3. Site Ispecific Imethylation
4. On Itranscriptome Ichanges
✓ If I"aza" Iis Iadded Ito IE.Coli Iin Iincreasing Iconcentrations, Iwhat Ihappens? IUn-methylated IDNA Iwill Iincrease
Iproportionally I(Since IDcm Iis Iinhibited)
✓ How Idoes Ihigh Iconc. Iof IAza Iaffect Ibacterial Igrowth? IHigh Iconc. Iof IAza Iinhibits Ibacterial Igrowth I(after I2
hours)
✓ a Idemethylating Iagent, Ihas Ibeen Iused Ias Ia Itherapeutic Idrug Iin Ithe Itreatment Iof Ileukemia Iand
Imyelodysplastic Isyndrome
✓ 5-azacytidine I(which Ireverses Ithe Ieffects Iof IDNA Imethyltransferases I[DNMTs]), Ihave Iproven Ieffective Iin
reactivating Isilenced Itumor-suppressor Igenes Iin Ithe Itreatment Iof Iselected IcancersI6.
Ithe Irole Iof Iinactive IMLH1 Iin Ithe Idevelopment Iof Isome Iforms Iof Iinherited Icolon Icancer.
✓ A Imajor Icause Iof Ione Iform Iof Iinherited Icolon Icancer I(hereditary Inonpolyposis Icolorectal Icancer I[HNPCC]) Iis Ithe
Imethylation Iof Ithe Ipromoter Iregion Iof Ia Igene, IMLH1, Iwhose Iprotein Iproduct Irepairs Idamaged IDNA. IWhen
IMLH1 Ibecomes Iinactive, IDNA Idamage Iaccumulates, Ieventually Iresulting Iin Icolon Itumors.
7. Effects Iof Iethanol Ion Ineural Istem Icells Iability Ito Idifferentiate Iinto Ifunctional Ineurons I(chap I13,wk I1) I(Chap I2
✓ The Imolecular Iactions Iof Iethanol Iare Ibelieved Ito Iinclude Isite-specific Ichanges Ito Ihistone Imodifications Iand
Ialterations Iof Ione-carbon Imetabolism Icausing Imethylation Ichanges.
✓ MicroRNA Iexpression Ihas Irecently Ibeen Ilinked Ito Ialcohol Iconsumption Iin Ia Icase-control Istudy Iof Ihead Iand
neck Icancer I(i.e., Ihead Iand Ineck Isquamous Icell Icarcinoma
✓
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