MCDB101BMolecularGeneticsII:Eukaryotes

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Instructor:

Rolf E. Christoffersen Office: Bio II, rm 3125 Office Hours: MW 11:00-12:00 or by appointment. e-mail: christof@lifesci.ucsb.edu Phone:805-893-3599

Teaching Assistants:Selvi ErsoyGeorgi Etimov-Boyn

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Text "Genetics:FromGenestoGenomes4th

ed.Edition"byHartwell,Hood,Goldberg,Reynolds,Silver,andVeres(2011)

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iClickerAny iClicker model will work. You might be able to buy a used original iClicker for less than $15 or borrow one.

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ExamsandGradesExams:(~95%ofgrade) Midterm1(Monday,April21) 100pt. Midterm2 (Monday,May12) 100pt. FinalExam(Fri.,June13th,12:003:00PM) 200pt.

ClassroomParticipation 20pt.1/2creditforparticipation1/2creditforcorrectanswer

DiscussionSectionParticipation 10pt.1pt foreachdiscussionsection

OnlineExercises: 9pt. 9pointsavailablethroughonlinequizzes(1pt perquizwith90%or

higherscore).Youmayretakeonlinequizzesuntilyouachieve90%ormore.

Grade: Total=439pt.

Yourgradeisbasedonthetotalaccumulationofpoints (439ptscale).

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Science of Learning

lecturereading

teaching

practice

discussion

demonstration

audio-visual

Science of Learning

From: How people learn by Mary Pat WenderothCo InE

DiscussionSections Discussionsectionsaremeetingthisweek! Attendanceisrequired. Discussionsectionswillprovidetheopportunityforstudentstoworkinsmallgroups.

Pleasecometodiscussionsectionpreparedtoaskquestionsandhavingalreadyattemptedsomeofthehomework.

Passivelylisteningtotheotherstudentsquestionsandsolutionswillnotbeveryvaluabletoyou beactivelyinvolvedinthediscussion!

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SelfAssessmentOnlineQuizzes

Onlineselfassessmentquizzes Immediatefeedback. Youmayrepeatexercisetoimprovescore 1pointforeachquizthatyoucompletewithascoreof

90%ormore. ~710daystocompletequizforextracredit

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8MCDB 101B: Molecular Genetics II: EukaryotesSpring 2014 Tentative Lecture Outline

DATE TOPIC CHAPTER3/31 Course mechanics and introduction to eukaryotic genetics 1

Review of basic Mendelian genetics and human pedigrees 2 Variations on simple dominance, multiple alleles, gene interactions and

biochemical pathways 3

Trinucleotide repeats and human genetic diseases; the evolution of gene families, Allelic variations: loss-of-function and gain-of-function alleles, dominant negative alleles

7 (pg 206-207,208-209)

8 (pg 277-280) Chromosome theory of inheritance, cell cycle, chromosome behavior in mitosis

and meiosis ,eukaryotic life cycles 4

Genetics of sex chromosomes, sex determination and dosage compensation mechanisms

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4/21 Midterm 1 (100 pts) Monday, April 21 Eukaryotic chromosome structure: nucleosomes, centromeres, telomeres, and

origin of replications 12

Recombination and basic gene mapping, statistical methods to evaluate real data, ordering genes with test crosses; mapping F1 crosses, effects of multiple crossovers; linkage mapping in humans

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Gene conversion and the double strand break model of recombination 6 (pg 189-193) RNA processing in eukaryotes: caps, splicing, poly(A) tails; mRNA export, mRNA

stability; translation in eukaryotes; mRNA quality control 8 (pg 259-265,

272-275) 5/12 Midterm 2 (100 pts) Monday, May 12

Review of molecular genetic techniques: enzymes, gels, blots, PCR, gene cloning and libraries

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Genome analysis: Reconstructing the genome from overlapping clones. 10 (pg 334-348, 359-361)

DNA Polymorphisms for gene mapping and forensicsLocalizing a disease locus on the human genome sequence: LOD scores and mapping recombination breakpoints Linkage disequilibrium; identifying candidate genes. Transgenics, targeted gene knockouts, RNAi, high density DNAarrays

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Genetics of changes in chromosome structure; deletions, duplications, inversions and translocations

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Eukaryotic gene expression; chromatin remodeling, basal transcription enhancers, activators, repressors, insulators

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6/13 Comprehensive Final Exam - (200 pts) Friday, June 13th 12:00-3:00 PM Co InE

Whatisthescienceofgenetics?

Thestudyofgenes:HowtheyarepassedontonextgenerationHowtheycontrolbiologicalfunctionHowtheychangeoverevolutionarytime

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GenesaresequencesofDNAthatoften encodeproteins

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DNAresidesinwithincellspackagedasunitscalledchromosomes

Theentirecollectionofchromosomesineachcellofanorganismiscalledagenome

Humanshave23pairsofchromosomes

Thehumangenomehasabout3x109 basepairsandestimated30,000 40,000genes

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ProteinsinteractwithDNAandotherproteins Biologicalsystemsfunctionascomplexinteractivenetworksof

proteinsandDNAthatinteractwithoneanother

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Manygeneshavesimilarfunctionsinverydifferentorganisms

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Cytochrome C from widely divergent species

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Rapidchangeinregulatorynetworksspecifyhowgenesbehave

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Genomesequencingprojectsareastepinunderstandingthecomplexityofgenomes

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http://www.hhmi.org/genesweshare/e400.html

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TheHumanGenome

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Socialissuesandgenetics

Shouldanindividualsgeneticprofilesbefreelyavailabletoinsurancecompanies,employers,government?

Shouldourgovernmentregulatetheuseofgeneticandgenomicinformationtoreflectsocietiessocialvalues?

Isitokaytopermanentlyaltergenesinhumansformedicalorsocialreasons?

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InheritanceofTraits

Fig 2.3 Like begets like and unlike

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GregorMendel

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Mendel'sExperiments

TruebreedingPeaplants Monohybridcross parentallinesdifferingbyonetrait

Dihybridcross parentallinesdifferingbytwotraits

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SevenTraits29

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Alternativeformsoftraitsarealleles

Eachtraitcarriestwocopiesofaunitofinheritance,oneinheritedfromthemotherandtheotherfromthefather

Alternativeformsofatraitarecalledalleles TraitsthatappearinF1aredominant TraitsthatarehiddeninF1arerecessive

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2.11

Reginald Punnett

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RulesofProbabilityIndependent events What is the probability that both A and B will occur?

Product rule = determine probability of each and multiply them together.

Mutually exclusive eventsWhat is the probability of A or B occurring?

Sum rule = determine the probability of each and add them together.

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Mendel did further crosses to verify the law of segregation

F2 plants were selfed to produce F3 progeny All of the green F2 peas were pure breeding

1/3 of the yellow F2 peas were pure breeding

2/3 of the yellow F2 peas were hybrids

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Fig. 2.12

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FiveTipsforFosteringLearningintheClassroom

Buildacommunityoflearners Makelearningrelevant. Letstudentsknowyoucareaboutthem. Incorporateactiveinvolvementforallstudents,alongwithhighexpectations.

Makelearningfun.

From: Faculty Focus by Karen Spencer

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Conclusion#1:Mendel'sLawofSegregation

Proposedtheexistenceofgenesthatarediscreteunitsofinheritance.

Genescomeinpairswitheachmemberofapaircalledanallele(indiploidslikepea).

Eachgametecarriesonlyoneallele Thetwoallelesofagenepairsegregateequallyintothegametes.

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Dihybrid crossesrevealthelawofindependentassortment

Adihybrid isanindividualthatisheterozygousattwogenes

Mendeldesignedexperimentstodetermineiftwogenessegregateindependentlyofoneanotherindihybrids

Firstconstructedtruebreedinglinesforbothtraits,crossedthemtoproducedihybrid offspring,andexaminedtheF2forparentalorrecombinanttypes(newcombinationsnotpresentintheparents)

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2.15Dihybrid Cross38

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2.16 39

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TestCrossfordihybrids

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Conclusion#2:Mendel'sLawofIndependentAssortment

Differentgenespairsassortindependentlyingameteformation.

Predictsagenotypicratioof1:1:1:1inthegametesproducedbyadihybrid (AaBb).

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SummaryofMendel'swork Inheritanceisparticulate notblending Therearetwocopiesofeachtraitinagermcell Gametescontainonecopyofthetrait Alleles(differentformsofthetrait)segregateintogametesinaratioof1:1

Allelesaredominantorrecessive thusthedifferencebetweengenotypeandphenotype

Differentgenesassortindependentlyfromeachother

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SolvedProblem2II

Tomato RedFruitdominantoveryellowfruit Purplestemsdominantovergreenstems Progenyfromaparticularcross

305redfruit,purplestems 328redfruit,greenstems 110yellowfruit,purplestems 97yellowfruit,greenstems

Whatwasthegenotypeoftheparentsinthiscross?

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Howdoproteinsdeterminephenotypes?44

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Some of the most common single-gene traits caused by recessive alleles in humans

Disease Effect Incidence of Disease

Thallassemia (chromosome 16 or 11)

Reduced amounts of hemoglobin; anemia, bone, and spleen enlargement

1/10 in parts of Italy

Sickle-cell anemia (chromosome 11)

Abnormal hemoglobin; sickle-shaped red cells, anemia, blocked circulation; increased resistance to malaria

1/625 African-Americans

Cystic fibrosis (chromosome 7)

Defective cell membrane protein; excessive mucus production; digestive and respiratory failure

1/2000 Caucasians

Tay-Sachs disease (chromosome 15)

Missing enzyme; buildup of fatty deposit in brain; buildup disrupts mental development

1/3000 Eastern European Jews

Phenylketonuria (PKU) (chromosome 12)

Missing enzyme; mental deficiency

1/10,000 Caucasians

Table 2.1

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Some of the most common single-gene traits caused by dominant alleles in humans

Disease Effect Incidence of Disease

Hypercholesterolemia (chromosome 19)

Missing protein that removes cholesterol from the blood; heart attack by age 50

1/122 French Canadians

Huntington disease (chromosome 4)

Progressive mental and neurological damage; neurologic disorders by ages 40 - 70

1/25,000 Caucasians

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Table 2.1

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HumanPedigreeAnalysis

Tracephenotypesinfamiliesthroughmultiplegenerations

UseMendelianrulestodeducemodesofinheritanceforhumangenetictraits

Genotypesofspecificindividualscanoftenbededuced

Makepredictionsbasedonparentalgenotypeandthemodeofinheritanceoftrait

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2.21 Huntington disease a rare dominant trait

http://www.med.harvard.edu/AANLIB/home.html

roentgen-ray computed tomography

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RelationshipbetweenCAGrepeatnumberandageatonset

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2.22 Cystic Fibrosis Recessive Trait49

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FinalExamQuestion 51

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Midterm 1 Question

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