Upload
lelouchdamien
View
13
Download
0
Embed Size (px)
DESCRIPTION
presentation of genetics second part of the course at UCSB
Citation preview
MCDB101BMolecularGeneticsII:Eukaryotes
1
Instructor:
Rolf E. Christoffersen Office: Bio II, rm 3125 Office Hours: MW 11:00-12:00 or by appointment. e-mail: [email protected] Phone:805-893-3599
Teaching Assistants:Selvi ErsoyGeorgi Etimov-Boyn
Co InE
Text "Genetics:FromGenestoGenomes4th
ed.Edition"byHartwell,Hood,Goldberg,Reynolds,Silver,andVeres(2011)
2
iClickerAny iClicker model will work. You might be able to buy a used original iClicker for less than $15 or borrow one.
Co InE
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).
3Co InE
010
20
30
40
50
60
70
80
90
100
1 2 3 4 5 6 7
A
v
g
.
R
e
t
e
n
t
i
o
n
R
a
t
e
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!
6Co InE
SelfAssessmentOnlineQuizzes
Onlineselfassessmentquizzes Immediatefeedback. Youmayrepeatexercisetoimprovescore 1pointforeachquizthatyoucompletewithascoreof
90%ormore. ~710daystocompletequizforextracredit
7Co InE
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
4
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
5
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
9
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
11
Genetics of changes in chromosome structure; deletions, duplications, inversions and translocations
13 (pg 429-447)
Eukaryotic gene expression; chromatin remodeling, basal transcription enhancers, activators, repressors, insulators
16
6/13 Comprehensive Final Exam - (200 pts) Friday, June 13th 12:00-3:00 PM Co InE
Whatisthescienceofgenetics?
Thestudyofgenes:HowtheyarepassedontonextgenerationHowtheycontrolbiologicalfunctionHowtheychangeoverevolutionarytime
10Co InE
GenesaresequencesofDNAthatoften encodeproteins
12Fig. 1.2
Co InE
DNAresidesinwithincellspackagedasunitscalledchromosomes
Theentirecollectionofchromosomesineachcellofanorganismiscalledagenome
Humanshave23pairsofchromosomes
Thehumangenomehasabout3x109 basepairsandestimated30,000 40,000genes
13Fig. 1.4Co InE
ProteinsinteractwithDNAandotherproteins Biologicalsystemsfunctionascomplexinteractivenetworksof
proteinsandDNAthatinteractwithoneanother
14Fig. 1.6Co InE
Manygeneshavesimilarfunctionsinverydifferentorganisms
15Fig. 1.8
Cytochrome C from widely divergent species
Co InE
Rapidchangeinregulatorynetworksspecifyhowgenesbehave
16Fig. 1.9Co InE
Genomesequencingprojectsareastepinunderstandingthecomplexityofgenomes
17Fig.1.12
http://www.hhmi.org/genesweshare/e400.html
Co InE
TheHumanGenome
18Co InE
Socialissuesandgenetics
Shouldanindividualsgeneticprofilesbefreelyavailabletoinsurancecompanies,employers,government?
Shouldourgovernmentregulatetheuseofgeneticandgenomicinformationtoreflectsocietiessocialvalues?
Isitokaytopermanentlyaltergenesinhumansformedicalorsocialreasons?
19Co InE
InheritanceofTraits
Fig 2.3 Like begets like and unlike
26A
Co InE
GregorMendel
27
Co InE
Mendel'sExperiments
TruebreedingPeaplants Monohybridcross parentallinesdifferingbyonetrait
Dihybridcross parentallinesdifferingbytwotraits
28
Co InE
SevenTraits29
Co InE
30
Co InE
Alternativeformsoftraitsarealleles
Eachtraitcarriestwocopiesofaunitofinheritance,oneinheritedfromthemotherandtheotherfromthefather
Alternativeformsofatraitarecalledalleles TraitsthatappearinF1aredominant TraitsthatarehiddeninF1arerecessive
31
Co InE
2.11
Reginald Punnett
33
Co InE
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.
34
Co InE
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
28
Fig. 2.12
34a
Co InE
FiveTipsforFosteringLearningintheClassroom
Buildacommunityoflearners Makelearningrelevant. Letstudentsknowyoucareaboutthem. Incorporateactiveinvolvementforallstudents,alongwithhighexpectations.
Makelearningfun.
From: Faculty Focus by Karen Spencer
Co InE
2.1335
Co InE
Conclusion#1:Mendel'sLawofSegregation
Proposedtheexistenceofgenesthatarediscreteunitsofinheritance.
Genescomeinpairswitheachmemberofapaircalledanallele(indiploidslikepea).
Eachgametecarriesonlyoneallele Thetwoallelesofagenepairsegregateequallyintothegametes.
36
Co InE
Dihybrid crossesrevealthelawofindependentassortment
Adihybrid isanindividualthatisheterozygousattwogenes
Mendeldesignedexperimentstodetermineiftwogenessegregateindependentlyofoneanotherindihybrids
Firstconstructedtruebreedinglinesforbothtraits,crossedthemtoproducedihybrid offspring,andexaminedtheF2forparentalorrecombinanttypes(newcombinationsnotpresentintheparents)
37
Co InE
2.15Dihybrid Cross38
Co InE
2.16 39
Co InE
TestCrossfordihybrids
2.1840
Co InE
Conclusion#2:Mendel'sLawofIndependentAssortment
Differentgenespairsassortindependentlyingameteformation.
Predictsagenotypicratioof1:1:1:1inthegametesproducedbyadihybrid (AaBb).
41
Co InE
SummaryofMendel'swork Inheritanceisparticulate notblending Therearetwocopiesofeachtraitinagermcell Gametescontainonecopyofthetrait Alleles(differentformsofthetrait)segregateintogametesinaratioof1:1
Allelesaredominantorrecessive thusthedifferencebetweengenotypeandphenotype
Differentgenesassortindependentlyfromeachother
42
Co InE
SolvedProblem2II
Tomato RedFruitdominantoveryellowfruit Purplestemsdominantovergreenstems Progenyfromaparticularcross
305redfruit,purplestems 328redfruit,greenstems 110yellowfruit,purplestems 97yellowfruit,greenstems
Whatwasthegenotypeoftheparentsinthiscross?
43
Co InE
Howdoproteinsdeterminephenotypes?44
Co InE
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
45a
Co InE
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
42
Table 2.1
45b
Co InE
HumanPedigreeAnalysis
Tracephenotypesinfamiliesthroughmultiplegenerations
UseMendelianrulestodeducemodesofinheritanceforhumangenetictraits
Genotypesofspecificindividualscanoftenbededuced
Makepredictionsbasedonparentalgenotypeandthemodeofinheritanceoftrait
46
Co InE
2.21 Huntington disease a rare dominant trait
http://www.med.harvard.edu/AANLIB/home.html
roentgen-ray computed tomography
47
Co InE
RelationshipbetweenCAGrepeatnumberandageatonset
48
Co InE
2.22 Cystic Fibrosis Recessive Trait49
Co InE
Co InE
FinalExamQuestion 51
Co InE
51
Midterm 1 Question
Co InE