NR 507 Week 4 Midterm Exam
I I I I I
Epigenetics
Defects Iin Ithe Iencoding Iof Ihistone-modifying Iproteins
Housekeeping IGenes Iare Ivital Ito Ithe Ifunction Iand Imaintenance Iof Iall Ithe Ibody’s Icells. IWhat Icharacteristic Iis I…
Iwith Ithese Igenes? I They Iare Itranscriptionally Iactive
Mutations Iin Ithe Iencoding Iof Ihistone Imodifying Iproteins I… Ishown Ito Iinfluence Ithe Idevelopment Iof IwhatIcongenital
Icondition? I Heart IDisease
Epigenetics Irefers Ito Ichemical Imodification Ithat Iare Imade Ito Iwhat? IHistones Iand IDNA
Signals Ito Ichange Ior Imodify Iepigenetic Itags Iare I… Ifrom Iwhere? IEnvironmental Ifactors. IHormones, IContact I(allIthe
Iabove)
What Isort Iof Imolecule Iis Iresponsible Ifor Itransferring Isignals Iinto Icells Ito Igen Iregulatory Iproteins? IKinases
Epigenetics Iand Iits Irole Ion Ihuman Idevelopment
Research Ihas Iprovided Isupport Ifor Ithe Itheory Ithat Iepigenetic Imodification Ican Iresult Ifrom Ideficient Iin Iutero
Inutrition Icausing? I Obesity Idiabetes Iand ICAD.
During Iwhich Istage Iof Ihuman Idevelopment Idoes Ithe Irole Iof Iepigenetics Ihave Ithe Igreatest Iimpact Ion Ithe
Idevelopment Iof Iepigenetic Iabnormalities? I In Iutero
The Idifference Ibetween IDNA Isequence Imutations Iand Iepigenetic Imodifications Iis? IThey Iare Isaid Ito Ibe
Ipluripotent. IUnlike IDNA Isequence Imutations Iwhich Icannot Ibe Ialtered, Iepigenetic Imodifications Ican Ibe
Ireversible.
Embryonic Istem Icells Iare Ipluripotent, Iwhich Ioriginated Ias Imass Icells Iwith Iblast Icyst I(not Ithe Iplacenta)
Epigenetics Iis Ithe Istudy Iof Iheritable Ichanges Iin Igene Iexpression Ior Iphenotype Icaused Iby Imechanisms Iother Ithan
changes Iin IDNA Isequences. IEpigenetic Imodifications Ican Icause Iindividuals Iwith Ithe Isame IDNA Isequences I(such
as Iidentical Itwins) Ito Ihave Idifferent Idisease Iprofiles. IThere Iare Ithree Imajor Itypes Iof Iepigenetic Imodifications
(Figure I6-1): IDNA Imethylation: IHistone Imodification IMicro-ribonucleic Iacids I(miRNAs Ior ImiRs):
Early Iin Iembryonic Idevelopment, Iall Icells Iof Ithe Iembryo Ihave Ithe Ipotential Ito Ibecome Iany Itype Iof Icell Iin Ithe
fetus Ior Iadult. IThese Iembryonic Istem Icells Iare Isaid Ito Ibe Ipluripotent. IA Ikey Ievent Iin Iearly Iembryogenesis Iis Ithe
differential Iepigenetic Imodification I(including Iextensive Imethylation) Iof Ispecific IDNA Inucleotide Isequences Iin
these Icells. IThis Imodification Ihelps Ito Idetermine Ithe Ifate Iof Ieach Icell I(i.e., Ithe Itype Iof Icell Iit Ibecomes, Isuch Ias Ia
myocyte, Ineuron, Ior Ifibroblast) Iby Ihelping Ito Iensure Ithat Ispecific Igenes Iare Iexpressed Ionly Iin Ithe Icells Iand Itissue
types Iin Iwhich Itheir Igene Iproducts Iare Ineeded I(e.g., Ifactor IVIII Iexpression Iprimarily Iin Ihepatocytes, Ior Idopamine
receptor Iexpression Iin Ineurons). IThus, Ieven Ithough Inearly Iall Icells Ihave Ithe Isame IDNA Isequence, Ithe
transcriptional Iactivity Iof Imost Igenes Ivaries Isubstantially Iand Idepends Ion Icell Iand Itissue Itype. IA Ismall
percentage Iof Igenes, Itermed Ihousekeeping Igenes, Iare Inecessary Ifor Ithe Ifunction Iand Imaintenance Iof Iall Icells.
These Igenes Iescape Ithe Imethylation Iprocess Iand Iremain Itranscriptionally Iactive Iin Iall Icells.
Much Iremains Ito Ibe Ilearned Iabout Ifactors Ithat Icause Iepigenetic Imodifications. IFindings Iso Ifar Iindicate Ithat
specific Ienvironmental Ior Inongenetic Ifactors, Isuch Ias Idiet Iand Iexposure Ito Icertain Ichemicals, Ican Idrive Isuch
modifications. IFor Iexample, Ialcohol Ihas Ibeen Ishown Ito Iaffect Imethylation Ipatterns Iin Ianimal Imodels,5 Iso Ithe
harmful Ieffects Iof Ifetal Ialcohol Iexposure Imay Ibe Imediated Ithrough Iepigenetic Imechanisms. IMaternal Idietary
deficiency Iduring Ipregnancy Imay Icause Iepigenetic Imodifications Iof Ifetal Igenes, Ileading Ito Ian Iincreased Irisk Iof
obesity Iand Idiabetes Iin Ithe Ioffspring Ilater Iin Ilife.6 IIn Isome Ianimal Imodels, Ithe Iinsulin-like Igrowth Ifactor I2 Igene
, (IGF2) Iis Ia Itarget Iof Ithese Iepigenetic Imodifications. IAlthough Ithe Iobserved Ichanges Iin Imethylation Istatus Iof ICpG
Isequences Iin Ithese Igenes Iare Itypically Ismall, Iit Iis Ipossible Ithat Ithey Iaffect Iphenotypic Idevelopment. IThe
Ihereditary Itransmission Iof Iepigenetic Ichanges Ito Isuccessive Igenerations Ihas Ibeen Itermed Iepigenetic
Itransgenerational Iinheritance. IIf Idemonstrated Ito Ioccur Iin Ihumans, Itransgenerational Iinheritance Icould Ihave
Iimportant Iimplications Ifor Idisease Iand Idisease Iprevention.
The Ibest Ievidence Ifor Iepigenetic Ieffects Ion Idisease Irisk Icomes Ifrom Istudies Iof Ihuman Icancer
Robust Iexperimental Iobservations Iare Iclarifying Ithe Iroles Iof Iepigenetic Istates Iin Idetermining Icell Ifates Iand
Idisease Iphenotypes. IThe Iwell-documented Iinvolvement Iof Iepigenetic Iabnormalities Iin Icarcinogenesis Iand Ithe
Imounting Ievidence Ifor Ithese Iepigenetic Ichanges Iin Iother Icommon Idiseases I(discussed Iin Iother Ichapters) Iwill
Ilikely Ielucidate Ipossibilities Ifor Ireversing Ithe Iepigenetic Iabnormalities Iand Ipreventing Itheir Iestablishment Iin
Iutero.
Totipotent Icells Iand Iits Iability Ito Idifferentiate Iinto Iany Itype Iof Icell
Which Iembryonic Istem Icell Icharacteristic Iis Ireferred Ito Ias Ia Itotipotent? IAbility Ito Idifferentiate Iinto Iany Itype Iof
Isomatic Icell.
Examples Iof Itwo Itotipotent Icells Iare? ISpores Iand Izygotes
What Iis Ia ITotipotent Icell? IOne Iof Ithe Imost Iimportant Istem Icell Ias Ithey Ihave Ithe Ipotential Ito Idevelop Iin Iany Icell
Ifound Iin Ithe Ihuman Ibody.
Are Iall Icells ITotipotent Icells? IOnly Ithe Imorula Icells Iare.
Prader-Willi Isyndrome Iand IAngelman Isyndrome?
What Icharacteristic Iof IPrader-Willi Isyndrome Iis Inot Ia Icharacteristic Iof IAngelman Isyndrome?
Mid-Mild-to-Moderate I retardation
Inherited Ifrom Ithe Ifather
A Ichild Iwith IPrader-Willi Isyndrome Ihas Ibeen Ihospitalized. IWhich Iassessment Ifindings Idoes Ithe Inurse IexpectIwith
Ithis Isyndrome? I Insatiable Ihunger I– Imorbid Iobesity
Prader-Willi Isyndrome Iwill Ihave Ishort Istature, Ihypotonia, Ismall Ihands, Ismall Ifeet, Iobesity,Ihypogonadism,
Iinverted IV-shape Iupper Ilip
The Inurse Iis Iexamining Ian I8-year-old Iboy Iwith Ichromosomal Iabnormalities. IWhich Isign, Ior Isymptom IsuggestsIthe
Iboy Ihas IAngelman Isyndrome? I Observation Ishows Ijerky Iataxic Imovements
Angelman Iis ISEVERE Imental Iretardation, Iseizures, Iataxic Igait, Iand Ibouts Iof Iuncontrolled Ilaughter IIs
Iinherited Iby Ithe Imother
A Iwell-known Idisease Iexample Iof Iimprinting Iis Iassociated Iwith Ia Ideletion Iof Iabout I4 Imillion Ibase Ipairs I(Mb)Iof
Ithe Ilong Iarm Iof Ichromosome I15. IWhen Ithis Ideletion Iis Iinherited Ifrom Ithe Ifather, Ithe Ichild Imanifests
IPrader-Willi Isyndrome, Iwhose Ifeatures Iinclude Ishort Istature, Ihypotonia, Ismall Ihands Iand Ifeet, Iobesity, Imild
Ito Imoderate Imental Iretardation, Iand Ihypogonadism. IThe Isame I4-Mb Ideletion, Iwhen Iinherited Ifrom Ithe
Imother, Icauses IAngelman Isyndrome, Iwhich Iis Icharacterized Iby Isevere Imental Iretardation, Iseizures, Iand Ian
Iataxic Igait
I I I I I
Epigenetics
Defects Iin Ithe Iencoding Iof Ihistone-modifying Iproteins
Housekeeping IGenes Iare Ivital Ito Ithe Ifunction Iand Imaintenance Iof Iall Ithe Ibody’s Icells. IWhat Icharacteristic Iis I…
Iwith Ithese Igenes? I They Iare Itranscriptionally Iactive
Mutations Iin Ithe Iencoding Iof Ihistone Imodifying Iproteins I… Ishown Ito Iinfluence Ithe Idevelopment Iof IwhatIcongenital
Icondition? I Heart IDisease
Epigenetics Irefers Ito Ichemical Imodification Ithat Iare Imade Ito Iwhat? IHistones Iand IDNA
Signals Ito Ichange Ior Imodify Iepigenetic Itags Iare I… Ifrom Iwhere? IEnvironmental Ifactors. IHormones, IContact I(allIthe
Iabove)
What Isort Iof Imolecule Iis Iresponsible Ifor Itransferring Isignals Iinto Icells Ito Igen Iregulatory Iproteins? IKinases
Epigenetics Iand Iits Irole Ion Ihuman Idevelopment
Research Ihas Iprovided Isupport Ifor Ithe Itheory Ithat Iepigenetic Imodification Ican Iresult Ifrom Ideficient Iin Iutero
Inutrition Icausing? I Obesity Idiabetes Iand ICAD.
During Iwhich Istage Iof Ihuman Idevelopment Idoes Ithe Irole Iof Iepigenetics Ihave Ithe Igreatest Iimpact Ion Ithe
Idevelopment Iof Iepigenetic Iabnormalities? I In Iutero
The Idifference Ibetween IDNA Isequence Imutations Iand Iepigenetic Imodifications Iis? IThey Iare Isaid Ito Ibe
Ipluripotent. IUnlike IDNA Isequence Imutations Iwhich Icannot Ibe Ialtered, Iepigenetic Imodifications Ican Ibe
Ireversible.
Embryonic Istem Icells Iare Ipluripotent, Iwhich Ioriginated Ias Imass Icells Iwith Iblast Icyst I(not Ithe Iplacenta)
Epigenetics Iis Ithe Istudy Iof Iheritable Ichanges Iin Igene Iexpression Ior Iphenotype Icaused Iby Imechanisms Iother Ithan
changes Iin IDNA Isequences. IEpigenetic Imodifications Ican Icause Iindividuals Iwith Ithe Isame IDNA Isequences I(such
as Iidentical Itwins) Ito Ihave Idifferent Idisease Iprofiles. IThere Iare Ithree Imajor Itypes Iof Iepigenetic Imodifications
(Figure I6-1): IDNA Imethylation: IHistone Imodification IMicro-ribonucleic Iacids I(miRNAs Ior ImiRs):
Early Iin Iembryonic Idevelopment, Iall Icells Iof Ithe Iembryo Ihave Ithe Ipotential Ito Ibecome Iany Itype Iof Icell Iin Ithe
fetus Ior Iadult. IThese Iembryonic Istem Icells Iare Isaid Ito Ibe Ipluripotent. IA Ikey Ievent Iin Iearly Iembryogenesis Iis Ithe
differential Iepigenetic Imodification I(including Iextensive Imethylation) Iof Ispecific IDNA Inucleotide Isequences Iin
these Icells. IThis Imodification Ihelps Ito Idetermine Ithe Ifate Iof Ieach Icell I(i.e., Ithe Itype Iof Icell Iit Ibecomes, Isuch Ias Ia
myocyte, Ineuron, Ior Ifibroblast) Iby Ihelping Ito Iensure Ithat Ispecific Igenes Iare Iexpressed Ionly Iin Ithe Icells Iand Itissue
types Iin Iwhich Itheir Igene Iproducts Iare Ineeded I(e.g., Ifactor IVIII Iexpression Iprimarily Iin Ihepatocytes, Ior Idopamine
receptor Iexpression Iin Ineurons). IThus, Ieven Ithough Inearly Iall Icells Ihave Ithe Isame IDNA Isequence, Ithe
transcriptional Iactivity Iof Imost Igenes Ivaries Isubstantially Iand Idepends Ion Icell Iand Itissue Itype. IA Ismall
percentage Iof Igenes, Itermed Ihousekeeping Igenes, Iare Inecessary Ifor Ithe Ifunction Iand Imaintenance Iof Iall Icells.
These Igenes Iescape Ithe Imethylation Iprocess Iand Iremain Itranscriptionally Iactive Iin Iall Icells.
Much Iremains Ito Ibe Ilearned Iabout Ifactors Ithat Icause Iepigenetic Imodifications. IFindings Iso Ifar Iindicate Ithat
specific Ienvironmental Ior Inongenetic Ifactors, Isuch Ias Idiet Iand Iexposure Ito Icertain Ichemicals, Ican Idrive Isuch
modifications. IFor Iexample, Ialcohol Ihas Ibeen Ishown Ito Iaffect Imethylation Ipatterns Iin Ianimal Imodels,5 Iso Ithe
harmful Ieffects Iof Ifetal Ialcohol Iexposure Imay Ibe Imediated Ithrough Iepigenetic Imechanisms. IMaternal Idietary
deficiency Iduring Ipregnancy Imay Icause Iepigenetic Imodifications Iof Ifetal Igenes, Ileading Ito Ian Iincreased Irisk Iof
obesity Iand Idiabetes Iin Ithe Ioffspring Ilater Iin Ilife.6 IIn Isome Ianimal Imodels, Ithe Iinsulin-like Igrowth Ifactor I2 Igene
, (IGF2) Iis Ia Itarget Iof Ithese Iepigenetic Imodifications. IAlthough Ithe Iobserved Ichanges Iin Imethylation Istatus Iof ICpG
Isequences Iin Ithese Igenes Iare Itypically Ismall, Iit Iis Ipossible Ithat Ithey Iaffect Iphenotypic Idevelopment. IThe
Ihereditary Itransmission Iof Iepigenetic Ichanges Ito Isuccessive Igenerations Ihas Ibeen Itermed Iepigenetic
Itransgenerational Iinheritance. IIf Idemonstrated Ito Ioccur Iin Ihumans, Itransgenerational Iinheritance Icould Ihave
Iimportant Iimplications Ifor Idisease Iand Idisease Iprevention.
The Ibest Ievidence Ifor Iepigenetic Ieffects Ion Idisease Irisk Icomes Ifrom Istudies Iof Ihuman Icancer
Robust Iexperimental Iobservations Iare Iclarifying Ithe Iroles Iof Iepigenetic Istates Iin Idetermining Icell Ifates Iand
Idisease Iphenotypes. IThe Iwell-documented Iinvolvement Iof Iepigenetic Iabnormalities Iin Icarcinogenesis Iand Ithe
Imounting Ievidence Ifor Ithese Iepigenetic Ichanges Iin Iother Icommon Idiseases I(discussed Iin Iother Ichapters) Iwill
Ilikely Ielucidate Ipossibilities Ifor Ireversing Ithe Iepigenetic Iabnormalities Iand Ipreventing Itheir Iestablishment Iin
Iutero.
Totipotent Icells Iand Iits Iability Ito Idifferentiate Iinto Iany Itype Iof Icell
Which Iembryonic Istem Icell Icharacteristic Iis Ireferred Ito Ias Ia Itotipotent? IAbility Ito Idifferentiate Iinto Iany Itype Iof
Isomatic Icell.
Examples Iof Itwo Itotipotent Icells Iare? ISpores Iand Izygotes
What Iis Ia ITotipotent Icell? IOne Iof Ithe Imost Iimportant Istem Icell Ias Ithey Ihave Ithe Ipotential Ito Idevelop Iin Iany Icell
Ifound Iin Ithe Ihuman Ibody.
Are Iall Icells ITotipotent Icells? IOnly Ithe Imorula Icells Iare.
Prader-Willi Isyndrome Iand IAngelman Isyndrome?
What Icharacteristic Iof IPrader-Willi Isyndrome Iis Inot Ia Icharacteristic Iof IAngelman Isyndrome?
Mid-Mild-to-Moderate I retardation
Inherited Ifrom Ithe Ifather
A Ichild Iwith IPrader-Willi Isyndrome Ihas Ibeen Ihospitalized. IWhich Iassessment Ifindings Idoes Ithe Inurse IexpectIwith
Ithis Isyndrome? I Insatiable Ihunger I– Imorbid Iobesity
Prader-Willi Isyndrome Iwill Ihave Ishort Istature, Ihypotonia, Ismall Ihands, Ismall Ifeet, Iobesity,Ihypogonadism,
Iinverted IV-shape Iupper Ilip
The Inurse Iis Iexamining Ian I8-year-old Iboy Iwith Ichromosomal Iabnormalities. IWhich Isign, Ior Isymptom IsuggestsIthe
Iboy Ihas IAngelman Isyndrome? I Observation Ishows Ijerky Iataxic Imovements
Angelman Iis ISEVERE Imental Iretardation, Iseizures, Iataxic Igait, Iand Ibouts Iof Iuncontrolled Ilaughter IIs
Iinherited Iby Ithe Imother
A Iwell-known Idisease Iexample Iof Iimprinting Iis Iassociated Iwith Ia Ideletion Iof Iabout I4 Imillion Ibase Ipairs I(Mb)Iof
Ithe Ilong Iarm Iof Ichromosome I15. IWhen Ithis Ideletion Iis Iinherited Ifrom Ithe Ifather, Ithe Ichild Imanifests
IPrader-Willi Isyndrome, Iwhose Ifeatures Iinclude Ishort Istature, Ihypotonia, Ismall Ihands Iand Ifeet, Iobesity, Imild
Ito Imoderate Imental Iretardation, Iand Ihypogonadism. IThe Isame I4-Mb Ideletion, Iwhen Iinherited Ifrom Ithe
Imother, Icauses IAngelman Isyndrome, Iwhich Iis Icharacterized Iby Isevere Imental Iretardation, Iseizures, Iand Ian
Iataxic Igait
