MCDB101B MolecularGeneticsII:Eukaryotes 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 Ersoy Georgi Etimov-Boyn

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Text
"Genetics:FromGenestoGenomes4th ed.Edition"byHartwell,Hood, Goldberg,Reynolds,Silver,andVeres (2011)

iClicker
Any 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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Exams:(~95%ofgrade) Midterm1(Monday,April21) Midterm2 (Monday,May12) FinalExam(Fri.,June13th,12:003:00PM) ClassroomParticipation

1/2creditforparticipation 1/2creditforcorrectanswer

ExamsandGrades
100pt. 100pt. 200pt. 20pt.

DiscussionSectionParticipation 10pt. 1pt foreachdiscussionsection OnlineExercises: 9pt. 9pointsavailablethroughonlinequizzes(1pt perquizwith90%or higherscore).Youmayretakeonlinequizzesuntilyouachieve90%or more. Grade: Total=439pt. Yourgradeisbasedonthetotalaccumulationofpoints (439ptscale).

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Science of Learning
Science of Learning
100 90 80 70 Avg. Retention Rate 60 50 40 30 20 10 0 1 2 3 4 5 6 7

teaching practice

discussion demonstration audio-visual reading

lecture

From: How people learn by Mary Pat Wenderoth

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DiscussionSections
Discussionsectionsaremeetingthisweek! Attendanceisrequired. Discussionsectionswillprovidetheopportunityfor studentstoworkinsmallgroups. Pleasecometodiscussionsectionpreparedtoask questionsandhavingalreadyattemptedsomeofthe homework. Passivelylisteningtotheotherstudentsquestions andsolutionswillnotbeveryvaluabletoyou be activelyinvolvedinthediscussion!

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SelfAssessmentOnlineQuizzes
Onlineselfassessmentquizzes Immediatefeedback. Youmayrepeatexercisetoimprovescore 1pointforeachquizthatyoucompletewithascoreof 90%ormore. ~710daystocompletequizforextracredit

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MCDB 101B: Molecular Genetics II: Eukaryotes Spring 2014 Tentative Lecture Outline

DATE 3/31

4/21

5/12

TOPIC Course mechanics and introduction to eukaryotic genetics Review of basic Mendelian genetics and human pedigrees Variations on simple dominance, multiple alleles, gene interactions and biochemical pathways Trinucleotide repeats and human genetic diseases; the evolution of gene families, Allelic variations: loss-of-function and gain-of-function alleles, dominant negative alleles Chromosome theory of inheritance, cell cycle, chromosome behavior in mitosis and meiosis ,eukaryotic life cycles Genetics of sex chromosomes, sex determination and dosage compensation mechanisms Midterm 1 (100 pts) Monday, April 21 Eukaryotic chromosome structure: nucleosomes, centromeres, telomeres, and origin of replications 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 Gene conversion and the double strand break model of recombination RNA processing in eukaryotes: caps, splicing, poly(A) tails; mRNA export, mRNA stability; translation in eukaryotes; mRNA quality control Midterm 2 (100 pts) Monday, May 12 Review of molecular genetic techniques: enzymes, gels, blots, PCR, gene cloning and libraries Genome analysis: Reconstructing the genome from overlapping clones. 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 Genetics of changes in chromosome structure; deletions, duplications, inversions and translocations Eukaryotic gene expression; chromatin remodeling, basal transcription enhancers, activators, repressors, insulators Comprehensive Final Exam - (200 pts) Friday, June 13th 12:00-3:00 PM

CHAPTER 1 2 3 7 (pg 206207,208-209) 8 (pg 277-280) 4 4

12 5 6 (pg 189-193) 8 (pg 259-265, 272-275) 9 10 (pg 334-348, 359-361) 11

13 (pg 429-447) 16

6/13

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Whatisthescienceofgenetics?

Thestudyofgenes:
Howtheyarepassedontonextgeneration Howtheycontrolbiologicalfunction Howtheychangeoverevolutionarytime

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GenesaresequencesofDNAthat often encodeproteins

Fig. 1.2
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DNAresidesinwithincellspackagedasunitscalled chromosomes

Theentirecollectionof chromosomesineachcellof anorganismiscalleda genome Humanshave23pairsof chromosomes Thehumangenomehas about3x109 basepairsand estimated30,000 40,000 genes
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Fig. 1.4

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ProteinsinteractwithDNAandotherproteins
Biologicalsystemsfunctionascomplexinteractivenetworksof proteinsandDNAthatinteractwithoneanother

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Fig. 1.6

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Manygeneshavesimilarfunctionsinvery differentorganisms

Cytochrome C from widely divergent species

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Fig. 1.8

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Rapidchangeinregulatorynetworksspecifyhowgenesbehave

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Fig. 1.9

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Genomesequencingprojectsareastepinunderstandingthe complexityofgenomes

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

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TheHumanGenome

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Socialissuesandgenetics
Shouldanindividualsgeneticprofilesbe freelyavailabletoinsurancecompanies, employers,government? Shouldourgovernmentregulatetheuseof geneticandgenomicinformationtoreflect societiessocialvalues? Isitokaytopermanentlyaltergenesin humansformedicalorsocialreasons?
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26A

InheritanceofTraits

Fig 2.3 Like begets like and unlike

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GregorMendel

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Mendel'sExperiments
TruebreedingPeaplants Monohybridcross parentallines differingbyonetrait Dihybridcross parentallinesdifferingby twotraits

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SevenTraits

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Alternativeformsoftraitsarealleles
Eachtraitcarriestwocopiesofaunitof inheritance,oneinheritedfromthemother andtheotherfromthefather Alternativeformsofatraitarecalledalleles TraitsthatappearinF1aredominant TraitsthatarehiddeninF1arerecessive

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2.11

Reginald Punnett

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RulesofProbability
Independent events What is the probability that both A and B will occur? Product rule = determine probability of each and multiply them together. Mutually exclusive events What 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

Fig. 2.12
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FiveTipsforFosteringLearningintheClassroom

Buildacommunityoflearners Makelearningrelevant. Letstudentsknowyoucareaboutthem. Incorporateactiveinvolvementforall students,alongwithhighexpectations. Makelearningfun.

From: Faculty Focus by Karen Spencer
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2.13

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Conclusion#1: Mendel'sLawofSegregation
Proposedtheexistenceofgenesthatare discreteunitsofinheritance. Genescomeinpairswitheachmemberofa paircalledanallele(indiploidslikepea). Eachgametecarriesonlyoneallele Thetwoallelesofagenepairsegregate equallyintothegametes.

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Dihybrid crossesrevealthelawof independentassortment

Adihybrid isanindividualthatisheterozygousattwo genes Mendeldesignedexperimentstodetermineiftwo genessegregateindependentlyofoneanotherin dihybrids Firstconstructedtruebreedinglinesforbothtraits, crossedthemtoproducedihybrid offspring,and examinedtheF2forparentalorrecombinanttypes (newcombinationsnotpresentintheparents)

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Dihybrid Cross

2.15

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2.16

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2.18

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TestCrossfor dihybrids

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Conclusion#2:Mendel'sLawof IndependentAssortment
Differentgenespairsassortindependently ingameteformation. Predictsagenotypicratioof1:1:1:1inthe gametesproducedbyadihybrid (AaBb).

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SummaryofMendel'swork
Inheritanceisparticulate notblending Therearetwocopiesofeachtraitinagermcell Gametescontainonecopyofthetrait Alleles(differentformsofthetrait)segregateinto gametesinaratioof1:1 Allelesaredominantorrecessive thusthe differencebetweengenotypeandphenotype Differentgenesassortindependentlyfromeach other

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SolvedProblem2II

Tomato
RedFruitdominantoveryellowfruit Purplestemsdominantovergreenstems Progenyfromaparticularcross
305redfruit,purplestems 328redfruit,greenstems 110yellowfruit,purplestems 97yellowfruit,greenstems

Whatwasthegenotypeoftheparentsinthis cross?

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Howdoproteinsdeterminephenotypes?

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Some of the most common single-gene traits caused by recessive alleles in humans
Disease Thallassemia (chromosome 16 or 11) Sickle-cell anemia (chromosome 11) Effect Reduced amounts of hemoglobin; anemia, bone, and spleen enlargement Abnormal hemoglobin; sickleshaped red cells, anemia, blocked circulation; increased resistance to malaria Defective cell membrane protein; excessive mucus production; digestive and respiratory failure Missing enzyme; buildup of fatty deposit in brain; buildup disrupts mental development Missing enzyme; mental deficiency Incidence of Disease 1/10 in parts of Italy

1/625 AfricanAmericans

Cystic fibrosis (chromosome 7) Tay-Sachs disease (chromosome 15) Phenylketonuria (PKU) (chromosome 12)

1/2000 Caucasians

1/3000 Eastern European Jews 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 Hypercholesterolemia (chromosome 19) Effect Missing protein that removes cholesterol from the blood; heart attack by age 50 Progressive mental and neurological damage; neurologic disorders by ages 40 - 70 Incidence of Disease 1/122 French Canadians

Huntington disease (chromosome 4)

1/25,000 Caucasians

Table 2.1

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HumanPedigreeAnalysis
Tracephenotypesinfamiliesthrough multiplegenerations UseMendelianrulestodeducemodesof inheritanceforhumangenetictraits Genotypesofspecificindividualscanoften bededuced Makepredictionsbasedonparental genotypeandthemodeofinheritanceof trait

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2.21 Huntington disease a rare dominant trait

roentgen-ray computed tomography

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

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2.22 Cystic Fibrosis Recessive Trait

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FinalExamQuestion

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Midterm 1 Question

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