Biology 2250Biology 2250Principles of GeneticsPrinciples of Genetics

AnnouncementsAnnouncements

Lab 4 Information: B2250 (Innes) webpageLab 4 Information: B2250 (Innes) webpage download and print before lab.download and print before lab.

Virtual fly: log in and practiceVirtual fly: log in and practice http://biologylab.awlonline.com/http://biologylab.awlonline.com/

B2250B2250Readings and ProblemsReadings and Problems

Ch. 4 p. 100 – 112 Prob: 10, 11, 12, 18, 19Ch. 4 p. 100 – 112 Prob: 10, 11, 12, 18, 19Ch. 5 p. 118 – 129 Prob: 1 – 3, 5, 6, 7, 8, 9Ch. 5 p. 118 – 129 Prob: 1 – 3, 5, 6, 7, 8, 9Ch. 6 p. 148 – 165 Prob: 1, 2, 3, 10Ch. 6 p. 148 – 165 Prob: 1, 2, 3, 10Ch. 7 p. 188 – 191 (Bacterial conjugation)Ch. 7 p. 188 – 191 (Bacterial conjugation)

Weekly Online QuizzesWeekly Online Quizzes

Marks Marks Oct. 14 - Oct. 25 Example Quiz 2** Oct. 14 - Oct. 25 Example Quiz 2** for logging in for logging in

Oct. 21- Oct. 25 Quiz 1 2Oct. 21- Oct. 25 Quiz 1 2Oct. 28 – Oct. 31 Quiz 2 2Oct. 28 – Oct. 31 Quiz 2 2Nov. 4 – Nov. 7 Quiz 3 2Nov. 4 – Nov. 7 Quiz 3 2Nov. 10 Quiz 4 2Nov. 10 Quiz 4 2

(Midterm 2 Thursday Nov. 17)(Midterm 2 Thursday Nov. 17)

Questions for practiceQuestions for practice1. Gene A and gene B are linked. A test cross produces 10 AaBb 1. Gene A and gene B are linked. A test cross produces 10 AaBb

progeny out of a total of 100. The estimated map distance progeny out of a total of 100. The estimated map distance between gene A and B is: a. 10 b. 20 c. 30 d. 40 e. 50between gene A and B is: a. 10 b. 20 c. 30 d. 40 e. 50

2. For the pedigree, indicate the most probably mode of inheritance 2. For the pedigree, indicate the most probably mode of inheritance for the rare trait. for the rare trait.

3. For the pedigree, what is the probability that the indicated female 3. For the pedigree, what is the probability that the indicated female will produce an affected child? will produce an affected child?

ExampleExample

Test CrossTest Cross AaBb X aabb AaBb X aabb

ab Exp. Obs.ab Exp. Obs. AB AaBb 25 10 AB AaBb 25 10 RR Ab Aabb 25 40 Ab Aabb 25 40 P P aB aaBb 25 40 aB aaBb 25 40 PP ab aabb 25 10 ab aabb 25 10 RR 100 100100 100

How to distinguish:How to distinguish:ParentalParental high freq. high freq.

RecombinantRecombinant low freq. low freq.

Quiz – 2 answersQuiz – 2 answers

http://http://webctwebct..munmun.ca:8900/.ca:8900/

Mendelian GeneticsMendelian Genetics

Topics:Topics: -Transmission of DNA during cell division-Transmission of DNA during cell division

Mitosis and MeiosisMitosis and Meiosis - Segregation - Segregation - Sex linkage (- Sex linkage (problem: how to get a white-eyed femaleproblem: how to get a white-eyed female))

- Inheritance and probability- Inheritance and probability - Independent Assortment- Independent Assortment - Mendelian genetics in humans- Mendelian genetics in humans

- Linkage- Linkage

- Gene mapping- Gene mapping

-Gene mapping in other organismsGene mapping in other organisms (fungi, bacteria)(fungi, bacteria)- Extensions to Mendelian Genetics- Extensions to Mendelian Genetics- Gene mutation- Gene mutation- Chromosome mutation- Chromosome mutation- Quantitative and population genetics- Quantitative and population genetics

Linkage MapsLinkage Maps

Useful:Useful: - studying recombination (variation)- studying recombination (variation) - study the structure of the genome- study the structure of the genome - study gene interaction (cis, trans)- study gene interaction (cis, trans) - diagnosis (marker gene linked to disease gene)- diagnosis (marker gene linked to disease gene) - constructing particular genetic combinations- constructing particular genetic combinations

Linkage MapsLinkage Maps

Mapping two genes:Mapping two genes:Test cross: AaBb x aabbTest cross: AaBb x aabb % RF = map distance% RF = map distance

3 point test cross:3 point test cross: - multiple crossovers undetected- multiple crossovers undetected - underestimate true map distance- underestimate true map distance

Gene MappingGene MappingRequirements:Requirements:

1. Genetic material from two different individuals1. Genetic material from two different individuals

2. Recombination2. Recombination

Examples: fungiExamples: fungi bacteriabacteria

Fungal GeneticsFungal Genetics

Fungi:Fungi: important organisms in the ecosystemimportant organisms in the ecosystem - decomposers- decomposers - pathogens- pathogens important for humansimportant for humans - food- food - pathogens- pathogens(Biology 4040 – Mycology)(Biology 4040 – Mycology)

Fun Facts About FungiFun Facts About Fungihttp://www.herbarium.usu.edu/fungi/funfacts/factindx.htm

FungiFungi

Neurospora crassaNeurospora crassa(bread mold)(bread mold)

Morphological mutantsMorphological mutants

Biochemical mutants (one gene, one enzyme)Biochemical mutants (one gene, one enzyme)

Linkage MapLinkage Map

Neurospora crassa Neurospora crassa Linkage group ILinkage group I

Fungus Life CycleFungus Life Cycle

vegetative stage haploidvegetative stage haploid +, - mating types+, - mating types brief diploid stage brief diploid stage meiosis meiosis

++

--

nn

nn2n2n

meiosismeiosis ++

--

nn

nn

sporesspores

Independent Assortment Independent Assortment Diploids Diploids Test CrossTest Cross

AaBb X AaBb X aabbaabb

gametes gametes abab 1/4 AB A1/4 AB AaaBBbb 1/4 Ab A1/4 Ab Aaabbbb 1/4 aB a1/4 aB aaaBBbb 1/4 ab a1/4 ab aaabbbb

4 phenotypes4 phenotypes

4 genotypes4 genotypes

Gamete PoolGamete PoolGametes: Products of many meiosesGametes: Products of many meioses all pooled togetherall pooled together A BA B a b AB AB ab ab AB aba b AB AB ab ab AB abP A BP A B ab ab AB ab ab ab AB ab AbAb AB AB GameteGameteP P a ba b AB AB aBaB ab ab AB AB ab ab AB AB poolpoolR R a Ba B ab AB AB ab ab AB AB abR R A bA b

Tetrad AnalysisTetrad Analysis

Some Fungi and algae: 4 products of a Some Fungi and algae: 4 products of a singlesingle meiosis can be recoveredmeiosis can be recoveredAdvantages:Advantages:1. haploid organism - no dominance1. haploid organism - no dominance2. examine a single meiosis - test cross not needed2. examine a single meiosis - test cross not needed3. small, easy to culture3. small, easy to culture4. Tetrad Analysis - map gene to centromere4. Tetrad Analysis - map gene to centromere

Ascus with ascosporesAscus with ascospores

Tetrad AnalysisTetrad AnalysisTypes of Tetrads:Types of Tetrads:1. Unordered - 4 products mixed together1. Unordered - 4 products mixed together2. Ordered (linear) - 4 products lined up, each2. Ordered (linear) - 4 products lined up, each haploid nucleus can be tracedhaploid nucleus can be traced back through meiosisback through meiosis3. Octads - mitotic division after meiosis3. Octads - mitotic division after meiosis 8 products (2 x 4)8 products (2 x 4)

**

Linear Linear Tetrad AnalysisTetrad AnalysisLife Cycle:Life Cycle:

aa

++

HaploidHaploid

aa

++

aa++

DiploidDiploid

4 4 haploid haploid productsproducts

aa

++

aa

++Mating: Mating: a x + a x + a /+ a /+

n n 2nn n 2n

+ = a+ = a++

MeiosisMeiosis

Linear Linear Tetrad AnalysisTetrad Analysis

8 h8 haploidaploid sporesspores

4 4 haploid haploid productsproducts

aa

aa++

aaaaaaaa

++++

mitosismitosis

(Octad)(Octad)

Linear Tetrad AnalysisLinear Tetrad Analysis

Two types of asci:Two types of asci:

1. no crossover----> first division segregation (M1. no crossover----> first division segregation (M II))

2. crossover between 2. crossover between gene and centromere-----> second division gene and centromere-----> second division segregation (Msegregation (MIIII))

Mapping gene to centromereMapping gene to centromere

aa++aa++

First DivisionFirst Divisionaaaaaaaa++++++++

No No CrossoverCrossover

First division segregationFirst division segregationAAAAAAAAaaaaaaaa

meiosis

Mapping gene to centromereMapping gene to centromere

aaaa++++

aaaa++++aaaa++++

Second divisionSecond division

crossovercrossover

Second division segregationSecond division segregationAAAAa**a**a**a**A**A**A**A**aaaa

** recombinant

11stst and 2 and 2ndnd Division segregation Division segregation

aa++aa++

First DivisionFirst Divisionaaaaaaaa++++++++

No No CrossoverCrossover

aaaa++++

aaaa++++aaaa++++

Second divisionSecond division

CrossoverCrossover

Mapping gene to centromereMapping gene to centromere

a + a + + aa + a + + a a + a + + aa + a + + a a + + a a +a + + a a + a + + a a +a + + a a + + a a + a ++ a a + a + + a a + a ++ a a + a + + a + a + a+ a + a + a + a + a + a+ a + a + a 43 43 3 4 3 4 Total = 10043 43 3 4 3 4 Total = 100I II

MMII = 86 = 86

MMIIII = 14 = 14

Mapping gene to centromereMapping gene to centromere

MMII = 86 M = 86 MIIII = 14 = 14

14/100 = 14 % of meioses showed a crossover14/100 = 14 % of meioses showed a crossover ½ ½ of the crossover products of the crossover products recombinantrecombinant

RF = RF = ½ ½ x 14 % = 7 % x 14 % = 7 % aa

7 m.u.7 m.u.

Tetrad AnalysisTetrad Analysis

Tetrads:Tetrads:

Ordered (linear)Ordered (linear):: map gene to centromere map gene to centromere

Sex in BacteriaSex in Bacteria

E. coliE. coli

Haploid

conjugation

Origin of Plasmid genes from Lactococcus lactis

Bacteria used to make cheese and yogurt

Plasmids: location of antibiotic resistant genes

Recombination in Bacteria and Recombination in Bacteria and virusesviruses

Human Health:Human Health: - antibiotic resistance- antibiotic resistance - new strains of bacterial and viral- new strains of bacterial and viral diseases (bird flu)diseases (bird flu) -horizontal gene transfer (between species)-horizontal gene transfer (between species)

Linkage: SummaryLinkage: Summary

• Recombination: generates new combinationsRecombination: generates new combinations (inter and intrachromosomal)(inter and intrachromosomal)• Genetic maps:Genetic maps: - genes linked on the same chromosome- genes linked on the same chromosome - location of new genes relative to genes - location of new genes relative to genes already mapped already mapped

Linkage: SummaryLinkage: Summary

• Hunting for genes (Human Diseases)Hunting for genes (Human Diseases) - genetic markers: DNA variation- genetic markers: DNA variation - co-inheritance with diseases using pedigree- co-inheritance with diseases using pedigree informationinformation - recombinants used to estimate linkage- recombinants used to estimate linkage

- MUN Medical Genetics- MUN Medical Genetics

Extensions to Mendelian Genetics Extensions to Mendelian Genetics Ch. 14 From Gene to PhenotypeCh. 14 From Gene to Phenotype

Readings: Ch. 14 p. 454 – 473 Readings: Ch. 14 p. 454 – 473 Problems: Ch. 14: 2, 3, 4, 5, 6, 7Problems: Ch. 14: 2, 3, 4, 5, 6, 7

Chapter 1 Chapter 1 Genes, environment, organism Genes, environment, organism

Phenotype =Phenotype = gene + env. + gene x env. + gene x gene gene + env. + gene x env. + gene x gene

Mendelian Genetics:Mendelian Genetics:

Genotype PhenotypeGenotype Phenotype Dominance ?Dominance ?

G x E interactionG x E interaction

Extensions to Mendelian Extensions to Mendelian Genetics Genetics

(Gene (Gene Phenotype) Phenotype)

1. Dominance1. Dominance2. Multiple alleles2. Multiple alleles3. Pleiotropy3. Pleiotropy44. Epistasis (gene interaction). Epistasis (gene interaction)55. Penetrance and expressivity. Penetrance and expressivity

Gene interactionGene interaction

1.1. Alleles at one gene DominanceAlleles at one gene Dominance

2.2. Different genes EpistasisDifferent genes Epistasis

1. Dominance1. Dominance

Location of heterozygote between Location of heterozygote between two two homozygoteshomozygotes

1. Complete1. Complete 2. No dominance 2. No dominance 3. Incomplete3. Incomplete (partial) (partial) 4. Codominance 4. Codominance

Homozygotes: AHomozygotes: A11AA1 1 AA22AA22 Heterozygote: Heterozygote: AA11AA22

Incomplete DominanceIncomplete Dominance

redred whitewhite

pinkpink

CodominanceCodominance

Human Blood Groups:Human Blood Groups:

Genotype PhenotypeGenotype Phenotype****

AA AAA A AB AB AB AB co-dominanceco-dominance

BB BBB B**** antigen protein on RBC antigen protein on RBC

CodominanceCodominance

Molecular MarkersMolecular Markers

AB AA BB BBAB AA BB BB

AA

BB

AlleleAllele

Heterozygote distinguished from homozygotesHeterozygote distinguished from homozygotes

2. Multiple Alleles2. Multiple Alleles(ABO Blood groups(ABO Blood groups - - 3 alleles3 alleles))

Genotype Genotype PhenotypePhenotype (6) (4)(6) (4)------------------------------------------------------------------------------------------ OO OOO O recessive recessiveAA, AO AAA, AO A dominant dominantBB, BO BBB, BO B dominant dominant AB ABAB AB co-dominant co-dominant------------------------------------------------------------------------------------------

Multiple alleles Multiple alleles in cloverin clover

Test for AllelismTest for AllelismPossibilities:Possibilities:

1. alleles for the same gene - all crosses show1. alleles for the same gene - all crosses show mendelian ratios (1:1 3:1 1:2:1)mendelian ratios (1:1 3:1 1:2:1)

2. more complex inheritance (> 1 gene)2. more complex inheritance (> 1 gene)

oror

Example: white, Example: white, yellowyellow, , pinkpink

Cross Cross F F11 F F22

white x white x yellowyellow yellowyellow 3:1 3:1 yellowyellow : white : whitewhite x white x pinkpink pink pink 3:1 3:1 pinkpink : white : whiteyellowyellow x x pinkpink pink pink 3:1 3:1 pinkpink : : yellowyellow

3 alleles: 3 alleles: w w y y pp 6 genotypes: 6 genotypes: w ww w y y y y p p p p p p w w yy w w y y pp

3. Pleiotropy3. Pleiotropy(one gene affects > 1 trait)(one gene affects > 1 trait)

Example: MouseExample: Mouse Gene affects:Gene affects: 1. coat colour (1. coat colour ( , , yellowyellow)) 2. survival2. survival

AAAA

Homozygous wildtypeHomozygous wildtype

dark

YellowYellowParentsParents

CrossesCrosses

A.A. x x -----> all-----> all

B.B. x x ---> ---> 1/21/2 1/ 1/22

C.C. x x ----> ----> 22//33 1/ 1/33

ExplanationExplanation

A. A. AA x AA all AAAA x AA all AA

B. B. AA x AA x AAYYA ½ A ½ AAYYA , ½ AAA , ½ AA

C. AC. AYYA x A x AAYYA ¼ AA ½ A ¼ AA ½ AAYYA ¼ A ¼ AAYYAAYY

diesdies 1 : 21 : 2

1/3 2/31/3 2/3

InterpretationInterpretation

Gene affects both coat colour andGene affects both coat colour and survivalsurvival

1. 1. AAYY dominantdominant to A for coat colour to A for coat colour

2. 2. AAYY recessiverecessive lethal for survival lethal for survival

PleiotropyPleiotropy

PhenotypePhenotype Genotype coat colour survivalGenotype coat colour survival

A A A A dark dark live live A A AAYY yellowyellow live live AAY Y AAYY ? die ? die

dark

PleiotropyPleiotropy Gene AGene A

Trait 1Trait 1

Trait 2Trait 2

EpistasisEpistasis Gene AGene A Trait Trait

Gene BGene B

G + E = PG + E = P

Gene interactionGene interaction

44. Epistasis. Epistasis(gene interaction)(gene interaction)

MMore than one gene affects a characterore than one gene affects a characterOOne gene pair masks or modifies the ne gene pair masks or modifies the expression of another gene pairexpression of another gene pair

AABB AABB xx aabb ----> AaBb aabb ----> AaBb x x AaBb ---> F AaBb ---> F22

FF11

DihybridDihybrid

FF22

AaBb x AaBbAaBb x AaBb

A- B- 9/16A- B- 9/16A- bb 3/16A- bb 3/16aa B- 3/16aa B- 3/16aa bb 1/16aa bb 1/16

4 distinct 4 distinct phenotypes (2 traits)phenotypes (2 traits)

(peas: shape, colour)(peas: shape, colour)

Epistasis:Epistasis: Gene A and Gene B interact Gene A and Gene B interact phenotype of 1 trait phenotype of 1 trait

Gene A and B Gene A and B unlinkedunlinked

EpistasisEpistasis(Bb(BbEeEe X Bb X BbEeEe))

Labrador retrieverLabrador retriever Coat Colour (B and Coat Colour (B and EE genes) genes)

FF22 Ratio Genotype Phenotype Ratio Ratio Genotype Phenotype Ratio

9/16 B- 9/16 B- EE- black 9/16- black 9/163/16 B- 3/16 B- eeee goldgold 4/164/163/16 bb 3/16 bb EE- brown 3/16- brown 3/161/16 bb 1/16 bb eeee goldgold Gene E allows colour depositionGene E allows colour deposition

1.1.

Allele Allele EE Allele B Allele B

GoldenGolden brown brown blackblack

B- B- eeee bb bb EE- B- - B- EE-- bb bb eeee

EpistasisEpistasis

EpistasisEpistasis(AaBb X AaBb)(AaBb X AaBb)

Example: Flower petal colourExample: Flower petal colour

FF22 Ratio Genotype Phenotype Ratio Ratio Genotype Phenotype Ratio

9/16 A- B- Purple 9/169/16 A- B- Purple 9/163/16 A- bb White 7/163/16 A- bb White 7/163/16 aa B- White 3/16 aa B- White 1/16 aa bb White1/16 aa bb White

2.2.

Gene B Gene AGene B Gene A

colourless colourless purplecolourless colourless purple(white) (white) (white) (white)

A-bb aaB- A- B-A-bb aaB- A- B-aabbaabb

5. Penetrance and Expressivity5. Penetrance and Expressivity

Phenotype:Phenotype: genotype, genetic background,genotype, genetic background, and environmentand environment

Variable ExpressionVariable Expression: Penetrance : Penetrance ExpressivityExpressivity

Penetrance:Penetrance:

percentage of individuals that show some percentage of individuals that show some degree of expression of a mutant genotypedegree of expression of a mutant genotype

Example: Polydactyly (P) Example: Polydactyly (P) extra digitsextra digits

pp Pp PPpp Pp PPnormal 10 % normal polydactylynormal 10 % normal polydactyly 90 % polydactyly90 % polydactyly

Expressivity: Expressivity: degree that a given genotype is expresseddegree that a given genotype is expressed phenotypically phenotypically

Example: Pp individuals which do expressExample: Pp individuals which do express the extra digitthe extra digitss can vary can vary

(a) extra digit on each hand and foot(a) extra digit on each hand and foot (b) extra digit on one hand only(b) extra digit on one hand only (c) complete digit or vestige(c) complete digit or vestige

Same genotype

Variable expressivity of piebald spotting in beagles

SummarySummary

- segregation and independent assortment- segregation and independent assortment can explain a variety of patterns ofcan explain a variety of patterns of genetic variationgenetic variation

- Phenotype = Genotype + EnvironmentPhenotype = Genotype + Environment

Genetic interaction: genotype, epistasis,Genetic interaction: genotype, epistasis, genetic backgroundgenetic background