Table Of ContentAaron Gardner · Sarah Stauff er
Lindsay Petley-Ragan · Philip Wismer
Dewi Ayu Kencana Ungu
Labster Virtual
Lab Experiments
Genetics of
Human Diseases
Labster Virtual Lab Experiments:
Genetics of Human Diseases
(cid:2) (cid:2)
Aaron Gardner Sarah Stauffer
(cid:2) (cid:2)
Lindsay Petley-Ragan Philip Wismer
Dewi Ayu Kencana Ungu
Labster Virtual Lab
Experiments:
Genetics of Human
Diseases
AaronGardner PhilipWismer
LabsterGroupApS LabsterGroupApS
KøbenhavnK,Denmark KøbenhavnK,Denmark
SarahStauffer DewiAyuKencanaUngu
LabsterGroupApS LabsterGroupApS
KøbenhavnK,Denmark KøbenhavnK,Denmark
LindsayPetley-Ragan
LabsterGroupApS
KøbenhavnK,Denmark
ISBN978-3-662-58743-0 ISBN978-3-662-58744-7(eBook)
https://doi.org/10.1007/978-3-662-58744-7
SpringerSpektrum
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Preface
Welcometothe“GeneticsofHumanDiseases”textbook,whichispartofthe“Lab-
sterVirtualLabExperiments”series.
Thisbookwillhelpyoutolearnthekeyconceptsunderlyinggeneticdiseasein
humanswhileapplyingyournewly acquired knowledgeina virtuallab environ-
ment.Ineachchapteryouwillbeintroducedtooneoffourvirtuallabsimulations
andthetrue-to-lifemissionsthatyouwillencounterwhenplayingthesimulations.
Studythetheorysectionpresentedineachofthechapterscloselyandyouwillbe
fullypreparedtomasterthechallengingtasksinthevirtuallab!
Finally,youwillfindlearningobjectivesandtechniquescoveredbythevirtual
labsimulationattheendofeachchaptertoeasilyalignitscontentwithyourexam
preparation.
Othertopicsinthe“LabsterVirtualLabExperiments”bookseriesinclude“Ba-
sic Genetics”, “Basic Biology” and “Basic Biochemistry” (see section “Further
VolumesintheLabsterVirtualLabExperimentsSeries”attheendofthebook).
AboutLabster
Labsterisacompanydedicatedtodevelopingvirtuallabsimulationsthatarede-
signed to stimulate students’ natural curiosity and highlight the connection be-
tweenscienceandtherealworld. Thesesimulationshavebeenshowntoimprove
theachievementoflearningoutcomesamongstudents,bymakingthelearningex-
periencemoreimmersiveandengaging. Thecontentofthisbookwascreatedby
the Labster team members Dr. Aaron Gardner, Dr. Sarah Stauffer, Dr. Lindsay
Petley-Ragan,PhilipWismer,DewiAyuKencanaUngu,andSilviaTjong.
v
vi Preface
AboutthisTextbook
Our genome is an amazing thing. Consistent enough between us that we’re all
human, but containing so much variation that we’re all individual. Some of the
variationinourgeneticcodehasno(known)effect,somedescribesthemanyways
wecandifferforexamplethecolorofourhairoreyes,andyetmorecanpredispose
ustocertaindiseases.
Inthisvolumewe’llfocusonthelatteraspectandcoverthreedistinctgenetic
diseasesordisorders,describingtheireffectandthevitaltechniquesusedtodetect
anddiagnosethem. Butwe’llendonamorepositivenote,describingoneofthe
waysscientistshopetousethepowerofgeneticstofixunderlyinghealthissues.
Throughoutyou’lllearn aboutcutting-edgetechniquesthatscientistsandhealth-
carepractitionersuseonadailybasis,andleavewithanewunderstandingofthe
GeneticsofHumanDiseases.
MonogenicDisorders
In the geneticage monogenicdisorders could bethoughtofas thesimplesttype
of genetic disorder. Arising from mutations in a single gene, it is often easy to
detectand trace thesedisorders throughapopulation, andpredict therisk ofoc-
currence infuture generations. However, whilerelatively easy to detectthey are
oftenfarfromeasytotreat,asyou’llseewhenweinvestigatecysticfibrosisinthe
MonogenicDisorderssimulation.Therefore,agoodunderstandingofthemolecu-
lartechniquesusedtodiagnosecysticfibrosis,andhowtocalculateriskisvitalin
limitingtheimpactofthediseaseonfamilies.
Cytogenetics
Molecular genetics isn’t the only tool that scientists and healthcare practitioners
have. Analyzing the number and structure of our chromosomes can be hugely
informative, and is routinely used to detect certain abnormalities as part of pre-
natal testing. In the Cytogenetics simulation you’ll use a genome-wide high-
resolutiontechnique(arraycomparativegenomichybridization)tocheckforchro-
mosomalcopynumberchanges.Willyoubeabletointerprettheresultsandinform
amother-to-beaboutthehealthofherfetus?
MedicalGenetics
We covered a “simple” monogenic disorder in the first chapter, but can we use
thesetechniquesinlessclear-cutcases?IntheMedicalGeneticssimulationyou’ll
investigatethecaseofapotentialfamilialcancer. Byusingthetechniquesyou’ve
Preface vii
developedintheprevioustwochaptersyouwillidentifythegeneofinterest,pre-
dict its inheritance pattern and ultimately help a family understand their risk of
disease.
ViralGeneTherapy
Finally, we will flip thingsaround and showhowscientists are attempting to fix
disease-causingregionsofourDNA.Virusesarenormallysomethingwewantto
avoid,butbymanipulatingtheirgeneticcodewecanmakethemworkfor,rather
thanagainstus. IntheViralGeneTherapysimulationyou’llworkonapromising
techniquetotreatamajorcauseofheartdiseasebyinsertingafunctionalhuman
gene,intolivinghearttissue. Whateffectwillyourexperimenthaveandwillyou
beabletofindacureforthisgeneticcondition?
HowtoAccesstheVirtualLabSimulations?
You can access the four virtual lab simulations included in this book at www.
labster.com/springer.
Ifyouhavepurchasedaprintedcopyofthistextbook,youwillfindavoucher
codeonthelastpage,whichgivesyoufreeaccesstothefoursimulationsforthe
durationofonesemester(sixmonths).
If you are using the e-book version, you can sign up and buy access to the
simulationsthroughthesamelink.
Please beaware thatthesix monthperiodstarts onceyousignin for thefirst
time.
If youhaveanyquestionsabouttheuseofthevoucher, youcan contactusat
[email protected].
Contents
1 MonogenicDisorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 MonogenicDisordersSimulation . . . . . . . . . . . . . . . . . . . 2
1.2 MonogenicDisordersTheoryContent . . . . . . . . . . . . . . . . 4
1.3 Let’sGetStarted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Furtherreading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2 Cytogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.1 CytogeneticsSimulation. . . . . . . . . . . . . . . . . . . . . . . . . 30
2.2 CytogeneticsTheoryContent. . . . . . . . . . . . . . . . . . . . . . 32
2.3 Let’sGetStarted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Furtherreading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
3 MedicalGenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3.1 MedicalGeneticsSimulation . . . . . . . . . . . . . . . . . . . . . . 46
3.2 MedicalGeneticsTheoryContent . . . . . . . . . . . . . . . . . . . 48
3.3 Let’sGetStarted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Furtherreading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
4 ViralGeneTherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
4.1 ViralGeneTherapySimulation . . . . . . . . . . . . . . . . . . . . 58
4.2 ViralGeneTherapyTheoryContent . . . . . . . . . . . . . . . . . 60
4.3 Let’sGetStarted . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Furtherreading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
FurtherVolumesintheLabsterVirtualLabExperimentsSeries . . . . . 75
ix
1
Monogenic Disorders
©LabsterApSunderlicensetoSpringerVerlagGmbH2019 1
A.Gardneretal.,LabsterVirtualLabExperiments:GeneticsofHumanDiseases,
https://doi.org/10.1007/978-3-662-58744-7_1
2 1 MonogenicDisorders
1.1 MonogenicDisordersSimulation
Joinateamofdoctorsandlearnaboutthebasicsofmonogenicdisordersandhow
toperformageneticriskassessmentbasedonfamilyhistoryandgenetictests. As
thenamesuggestsmonogenicdisordersariseduetomutationsorchangesinasin-
glegene. Cysticfibrosis (CF) is themostcommonlife-limiting geneticdisorder
inthoseofNorthEuropeandescent,estimatedtoaffect70,000peopleworldwide.
CFisamonogenicdisordercausedbyoneofover2000disease-causingmutations
inthecysticfibrosistransmembraneconductanceregulator(CFTR)gene. Impor-
tantly,asarecessivedisorder,bothcopiesofthegenemustcarrymutationsforthe
diseasetomanifest.
LearnAboutCysticFibrosisandhowItIsDetectedGenetically
Predominantlypresentwithinthecellmembraneofepithelialcells,theCFTRpro-
tein is a chloride channel that regulates epithelial surface fluid secretion in the
respiratory and gastrointestinalsystems as well as numerous other epithelial tis-
sues. InCFmutationsintheCFTRgeneleadtoareduction,orcompleteloss,of
CFTR function. These mutations can be detected by several techniques, includ-
ingpolymerasechainreaction(PCR)tocheckforchangesinCFTRproteinlength
(Fig.1.1).
Fig.1.1 AlabassistantexplainshowtousePCRandgelelectrophoresistodetectmutations
inCFTRintheMonogenicDisorderssimulation
