Biology 2250 Principles of Genetics Announcements Lab 3 Information: B2250 (Innes) webpage Lab 3 Information: B2250 (Innes) webpage download and print before lab. download and print before lab. Virtual fly: log in and practice Virtual fly: log in and practice people that have ALREADY picked up their exams should see Dr. Carr for a re-marking people that have ALREADY picked up their exams should see Dr. Carr for a re-marking of p. 2 of p. 2

Weekly Online Quizzes Marks Marks Oct Oct. 25 Example Quiz 2** for logging in Oct. 21- Oct. 25 Quiz 1 2 Oct. 28 Quiz 2 2 Nov. 4 Quiz 3 2 Nov. 10 Quiz 4 2

B2250 Readings and Problems Ch. 4 p. 100 – 112 Prob: 10, 11, 12, 18, 19 Ch. 5 p. 118 – 129 Prob: 1 – 3, 5, 6, 7, 8, 9 Ch. 6 p. 148 – 165 Prob: 1, 2, 3, 10

Mendelian Genetics Topics: -Transmission of DNA during cell division -Transmission of DNA during cell division Mitosis and Meiosis Mitosis and Meiosis - Segregation - Segregation - Sex linkage (problem: how to get a white-eyed female) - Sex linkage (problem: 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 - Tetrad Analysis (mapping in fungi) - Extensions to Mendelian Genetics - Gene mutation - Chromosome mutation - Quantitative and population genetics     

Mendelian Inheritance Determining mode of inheritance: - single gene or more complicated - single gene or more complicated - recessive or dominant - recessive or dominant - sex linked or autosomal - sex linked or autosomal Approach: cross parents observed progeny observed progeny compare with expected compare with expected

Equal segregation of two members of a gene pair Aa ½ A gametes ½ a gametes P(a) = ½ P(A) = ½ Meiosis: diploid nucleus divides diploid nucleus divides produces haploid nuclei produces haploid nuclei Mendel’s First Law

Mendel’s Second Law Independent assortment: during gamete formation, the segregation of one gene pair is independent of other gene pairs. during gamete formation, the segregation of one gene pair is independent of other gene pairs.

Two Characters Monohybrid Cross parents differ for a single character parents differ for a single character (single gene ); seed shape (single gene ); seed shape Dihybrid Cross parents differ for two characteristics parents differ for two characteristics (two genes) (two genes)

Dihybrid Two Characters: 1. Seed colour yellow green Y y Y y 2. Seed shape Round wrinkled R r R r 4 phenotypes

Dihybrid RRyy X rrYY Ry rY Ry rY RrYy DIHYBRID RrYy DIHYBRID P F1F1F1F1 Gametes

F 1 Dihybrid ----->F 2 F 1 RrYy RrYy X RrYy RrYy X RrYy F round, yellow round, green round, green wrinkled, yellow wrinkled, yellow 1 32 wrinkled, green 1 32 wrinkled, green Total 556 Total 556

Producing the F 2 YyRr X YyRr YyRr X YyRr 1. F 1 Gametes  produce F 2 1. F 1 Gametes  produce F 2 2. Genotypes 2. Genotypes 3. Phenotypes 3. Phenotypes F1F1F1F1 F2F2F2F2

Independent Assortment Two gene systems: 1. Gametes from dihybrid 4 x 4 = 16 YyRr: YyRr: ¼ YR Yr yR yr ¼ YR Yr yR yr ¼ YR 1/16YYRR ¼ YR 1/16YYRR Yr Yr yR yR yr yr Male gametes Femalegametes F2F2F2F2

Independent Assortment 2. F 2 Genotypes 3 x 3 = 9 ¼ RR ½ Rr ¼ rr ¼ RR ½ Rr ¼ rr ¼ YY 1/16 YYRR ¼ YY 1/16 YYRR ½ Yy ½ Yy ¼ yy ¼ yy F2F2F2F2 YyRr X YyRr

Independent Assortment 3. F 2 Phenotypes 2 x 2 = 4 ¾ R- ¼ rr ¾ R- ¼ rr ¾ Y- 9/16 R-Y- ¾ Y- 9/16 R-Y- ¼ yy ¼ yy YyRr X YyRr

F1F1 9 Genotypes4 phenotypes YY RR YY Rr Yy RR Yy Rr YY rr Yy rr yy RR yy Rr yy rr YyRr x YyRr Y-R- Y-rr yyR- yyrr

Independent Assortment Any number of independent genes: Genes Phenotypes Genotypes (2 x2) 9 (3 x 3) 2 4 (2 x2) 9 (3 x 3) 3 8 (2x2x2) 27 (3 x 3 x 3) 3 8 (2x2x2) 27 (3 x 3 x 3) n 2 n 3 n n 2 n 3 n

Mendelian Genetics in Humans Determining mode of inheritance Problems: 1. long generation time 1. long generation time 2. can not control mating 2. can not control matingAlternative: * information from matings that have already occurred “Pedigree” * information from matings that have already occurred “Pedigree”

Human Pedigrees Pedigree analysis: trace inheritance of disease or condition trace inheritance of disease or condition provide clues for mode of inheritance provide clues for mode of inheritance (dominant vs. recessive) (dominant vs. recessive) (autosomal vs. sex linked) (autosomal vs. sex linked) however, some pedigrees ambiguous however, some pedigrees ambiguous

Human Pedigrees 1. Ambiguous: 2. Unambiguous: 1. Ambiguous: 2. Unambiguous: Affectedfemale Normalmale Normalfemale

Clues (non sex-linked) Recessive: 1. individual expressing trait has two 1. individual expressing trait has two normal parents normal parents 2. two affected parents can not have an 2. two affected parents can not have an unaffected child. unaffected child.

Rare Recessive A- A- (AA or Aa) Cousins(inbreeding) Rare = AA

Clues Dominant: 1. every affected person has at least one 1. every affected person has at least one affected parent affected parent 2. each generation will have affected 2. each generation will have affected individuals individuals

Dominant All genotypes known Not AA

Examples Recessive: - phenylketonuria (PKU) - phenylketonuria (PKU) - hemophilia (sex linked) - hemophilia (sex linked) - cystic fibrosis - cystic fibrosis - albinism - albinismDominant: - huntingtons chorea - huntingtons chorea - brachydactyly (short fingers) - brachydactyly (short fingers) - polydactyly (extra fingers) - polydactyly (extra fingers) - achondroblasia (dwarf) - achondroblasia (dwarf)

2n = 46

Brachydactyly Bb short fingers bb normal Bbbb

lian_genetics.html lian_genetics.html Online Tutorial:

Solving Genetics Problems 1.Don’t panic! 2.Carefully read the problem 3.What information is given? Know the terms used. 4.What aspect of genetics does the problem address?

X-linked Dominant 1. affected male ---> all daughters affected no sons no sons aa x AY ----> Aa, aY aa x AY ----> Aa, aY 2. affected female ----> ½ sons, ½ daughters affected affected Aa x aY ----> AY, aY, aa, Aa Aa x aY ----> AY, aY, aa, Aa * * * * Sex Linked Inheritance

X-Linked Dominant All daughters affected, no sons 1/2 daughters affected, 1/2 sons affected

X-linked Inheritance X-linked recessive: 1. more males than females show recessive phenotype recessive phenotype 2. affected female > both mother and father have recessive allele and father have recessive allele A a x a Y > a a A a x a Y > a a

X-linked Inheritance X-linked recessive: 3. affected male ----> mother carries allele A a x AY -----> a Y A a x AY -----> a Y 4. affected male -----> no affected offspring AA x a Y ----> AY, Aa AA x a Y ----> AY, Aa carrier

X-Linked Recessive Mothercarrier

Sex Linked Inheritance (examples) X linked genes Humans: - colour blindness Humans: - colour blindness - hemophilia - hemophilia More common in males (hemizygous aY) More common in males (hemizygous aY) X linked recessives expressed X linked recessives expressed

X-linked recessive hemophilia Queen Victoria (carrier) QE II Hemophilic male Carrier female

X – linked disease genes

Mendelian Genetics Topics: -Transmission of DNA during cell division -Transmission of DNA during cell division Mitosis and Meiosis Mitosis and Meiosis - Segregation (Monohybrid) - Segregation (Monohybrid) - Sex linkage - Sex linkage - Inheritance and probability - Inheritance and probability - Independent Assortment (Dihybrid) - Independent Assortment (Dihybrid) - Mendelian genetics in humans (Pedigree) - Mendelian genetics in humans (Pedigree)

Mendel’s Second Law Independent assortment: during gamete formation, the segregation of one gene pair is independent of other gene pairs. during gamete formation, the segregation of one gene pair is independent of other gene pairs. Genes independent because they are on different chromosomes Genes independent because they are on different chromosomes

Independent Assortment F 1 AaBb X AaBb F 1 AaBb X AaBb F 2 9 A-B- F 2 9 A-B- 3 A-bb 3 A-bb 3 aaB- 3 aaB- 1 aabb 1 aabb 4 phenotypes AABBAaBbAaBBAABb Genotypes Aabb, AAbb aaBb, aaBB

Independent Assortment Test Cross AaBb X aabb AaBb X aabb gametes ab gametes ab 1/4 AB AaBb 1/4 AB AaBb 1/4 Ab Aabb 1/4 Ab Aabb 1/4 aB aaBb 1/4 aB aaBb 1/4 ab aabb 1/4 ab aabb 4 phenotypes 4 genotypes

Fig 6-6 Independent Assortment Interchromosomal Recombination AB AB ab ab Ab Ab aB aB Inferred F 1 gamete types

A a B b A a b B Meiosis I OR (Genes) Correlation of genes and Chromosomes during meiosis A a 4 gamete types

Linkage of Genes - Many more genes than chromosomes - Many more genes than chromosomes - Some genes must be linked on the same chromosome; therefore not independent - Some genes must be linked on the same chromosome; therefore not independent

Complete Linkage P A B a b A B a b F 1 A B a b AaBb a b AaBb F 1 gametes A B AB Parental Parental Parental a b ab a b ab X dihybrid

Recombinant Gametes ? Crossing over: - exchange between homologous chromosomes - exchange between homologous chromosomes

Crossing over in meiosis I Meiosis I - homologous chromosomes pair - homologous chromosomes pair - reciprocal exchange between non-sister - reciprocal exchange between non-sister chromatids chromatids Ch 4 meiosis animation:

Crossing over in meiosis I (animation)

Gamete Types F 1 A B a b AaBb a b AaBb gametes A B AB Parental a b ab Parental a b ab Parental A b Ab Recomb. A b Ab Recomb. a B aB Recomb. a B aB Recomb.

1. Ways to produce dihybrid A B a b A B AaBb A B AaBb a b (dihybrid ) a b (dihybrid ) Gametes: Gametes: AB P AB P ab P ab P Ab R Ab R aB R aB R X P Cis Note: Chromatids omitted

2. Ways to produce dihybrid A b a B A b a B AaBb A b trans AaBb A b trans (dihybrid ) a B (dihybrid ) a B Gametes: Gametes: P Ab P Ab P aB P aB R AB R AB R ab R ab X P

Two ways to produce dihybrid A B a b A b a B cis A B AaBb A b trans a b (dihybrid ) a B a b (dihybrid ) a BGametes: AB P Ab AB P Ab ab P aB ab P aB Ab R AB Ab R AB aB R ab aB R ab XX P

Fig 6-6 Independent Assortment Linkage Fig 6-11 InterchromosomalIntrachromosomal

Example Test Cross AaBb X aabb ab Exp. Obs. ab Exp. Obs. AB AaBb R AB AaBb R Ab Aabb P Ab Aabb P aB aaBb P aB aaBb P ab aabb R ab aabb R How to distinguish: Parental  high freq. Recombinant  low freq.

Example (cont.) Gametes: AB R Gametes: AB R Ab P Ab P aB P aB P ab R ab R Therefore dihybrid: Therefore dihybrid: A b (trans) A b (trans) a B a B

Linkage Maps Genes close together on same chromosome: - smaller chance of crossovers - smaller chance of crossovers between them between them - fewer recombinants - fewer recombinantsTherefore: percentage recombination can be percentage recombination can be used to generate a linkage map used to generate a linkage map

Linkage maps A B large # of recomb. a b C D small number of recombinants c d Alfred Sturtevant (1913)

Linkage maps example Testcross progeny: P AaBb 2146 P AaBb 2146 R Aabb 43 R Aabb 43 R aaBb 22 R aaBb 22 P aabb 2302 P aabb 2302 Total map units Total map units = 1.4 % RF A 1.4 mu B

Additivity of map distances separate maps A B A C separate maps A B A C combine maps C A B or Locus or Locus A C B (pl. loci) A C B (pl. loci)

Summary Mendelian Genetics: Mendelian Genetics: Monohybrid cross (segregation): Monohybrid cross (segregation): - ratios (3:1, 1:2:1, 1:1) - ratios (3:1, 1:2:1, 1:1) - dominance, recessive - dominance, recessive - autosomal, sex-linked - autosomal, sex-linked - probability - probability - pedigrees - pedigrees Dihybrid Cross (Indep. Assort.): - ratios (9:3:3:1, 1:1:1:1) - ratios (9:3:3:1, 1:1:1:1) - linkage (deviation from I.A.) - linkage (deviation from I.A.) - recombination - recombination - linkage maps - linkage maps

Linkage Deviations from independent assortment Dihybrid  gametes 2 parent (noncrossover) common 2 parent (noncrossover) common 2 recombinant (crossover) rare 2 recombinant (crossover) rare % recombinants a function of distance between genes genes % RF = map distance

Linkage maps Tomato Drosophila