Classical Genetics

Classical genetics deals with the study of heredity Often referred to as Mendelian genetics Based on the principles first set forth by Gregor Mendel in 1866 Austrian monk studying traits of pea plants Early analysis of organismal traits was based on morphological characteristics Prior to Mendel, blending of traits was standard idea Later rejected due to subsequent reappearance of traits in offspring Mendel studied seven traits: seed shape, seed color, flower color, pod shape, pod color, flower and pod position, and stem length Traits occurred in two different forms His results were largely ignored until 1900

Mendel’s Peas Petal Stamen Carpel

Pea plant traits Flower color Purple White Flower position Axial Terminal Seed color Yellow Green Seed shape Round Wrinkled Pod shape Inflated Constricted Pod color Green Yellow Stem length Tall Dwarf

Mendel theorized that discrete heritable factors are passed from parent to offspring Following traits through multiple generations provided evidence to predict how traits could be passed on Mendel cross-fertilized peas of his choosing based on desired characteristics through controlled matings Called first generation the P1 (parental) generation Differed by one trait (hybrid) Offspring of the P generation were F1 generation Offspring of F1generation were F2 generation (dihybrid) He made several important discoveries based on observations of experiments

LE 9-2c Removed stamens from purple flower White Stamens Carpel Transferred pollen from stamens of white flower to carpel of purple flower Parents (P) Purple Pollinated carpel matured into pod Planted seeds from pod Offspring (F1)

have purple flowers have white flowers LE 9-3a P generation (true-breeding parents)  Purple flowers White flowers F1 generation All plants have purple flowers Fertilization among F1 plants (F1  F1) F2 generation 3 4 of plants 1 4 of plants have purple flowers have white flowers

Mendel’s Observations & Hypotheses Some traits disappeared in F1 generation but reappeared in F2 generation in particular ratios Some traits mask or dominate expression of the other trait: dominant form Some traits are masked by expression of dominant trait: recessive form Offspring get alternative forms of discrete heritable factors (genes) that account for variation in traits passed down: alleles Organisms receive one allele from each parent Supported by law of segregation: one allele on each chromosome of a (homologous) pair

Homologous Chromsomes Alternate forms of the genes (alleles) reside at the same locus on homologous chromosomes Supports law of segregation Either allele may be present, location is the constant Identical alleles: homozygous Differing alleles: heterozygous

LE 9-4 Gene loci Dominant allele P a B P a b Recessive allele Genotype: PP aa Bb Homozygous for the dominant allele Homozygous for the recessive allele Heterozygous

Mendel’s Conclusions Organism’s appearance doesn’t necessarily reflect its genetic makeup Genotype is genetic makeup Phenotype is expression of traits In monohybrid cross, 3:1 phenotypic ratio and 1:2:1 genotypic ratio Used a Punnett square to demonstrate possible combinations of crosses

Genetic makeup (alleles) LE 9-3b Genetic makeup (alleles) P plants PP pp Gametes All P All p F1 plants (hybrids) All Pp Gametes 1 2 1 2 P p Sperm P p F2 plants Phenotypic ratio 3 purple : 1 white P PP Pp Eggs Genotypic ratio 1 PP : 2 Pp : 1 pp p Pp pp

Dihybrid Crosses Mating a parental generation differing in two traits Results of mating F1 generations produce F2 generation Can be used to demonstrate independent assortment: alleles of two different genes segregate independently of one another Demonstrates alleles segregating independently of one another during gametogenesis Phenotypic ratio of 9:3:3:1, genotypic ratio of 1:2:2:4:2:1:1:2:1 (forget it!)

contradict hypothesis LE 9-5a Hypothesis: Dependent assortment Hypothesis: Independent assortment P generation RRYY rryy rryy RRYY rryy Gametes RY ry Gametes RY  ry F1 generation RrYy RrYy Sperm Sperm 1 4 RY 1 4 rY 1 4 Ry 1 4 ry 1 2 RY 1 2 ry 1 4 RY 1 2 RY RRYY RrYY RRYy RrYy F2 generation Eggs 1 4 rY 1 2 ry RrYY rrYY RrYy rrYy Eggs Yellow round 1 4 Ry 9 16 RRYy RrYy RRyy Rryy 3 16 Green round Actual results contradict hypothesis 1 4 ry Yellow wrinkled RrYy rrYy Rryy rryy 3 16 Actual results support hypothesis 1 16 Green wrinkled

Independent Assortment Example: Coat color and vision in Labs Black or chocolate coat: B or b Normal vision or PRA: N or n Blind Blind Phenotypes Genotypes Chocolate coat, blind (PRA) bbnn Black coat, normal vision B_N_ Black coat, blind (PRA) B_nn Chocolate coat, normal vision bbN_ Mating of heterozygotes (black, normal vision) BbNn  BbNn 9 black coat, normal vision 3 black coat, blind (PRA) 3 chocolate coat, normal vision 1 chocolate coat, blind (PRA) Phenotypic ratio of offspring

Discovering Genotypes Test crosses can be used to determine genotype Homozygous recessive organism is mated with organism of dominant phenotype to determine genotype Phenotypic ratio of F1 generation will allow determination of genotype

Two possibilities for the black dog: LE 9-6 Testcross:  Genotypes B_ bb Two possibilities for the black dog: BB or Bb Gametes B B b b Bb b Bb bb Offspring All black 1 black : 1 chocolate

Genetics and Probability Mendel’s laws follow predictable rules of probability Events following rules of probability occur independently of one another Current genetic configuration does not influence future outcome: sex in subsequent offspring Multiplication rule: probability of two events occurring simultaneously is product of the probabilities of the separate events( ½ X ½ = ¼ ) Addition rule: probability that event can occur in two or more alternative ways is the sum of the separate probabilities of the different ways (¼ + ¼ = ½) Can be used to predict probability of combinations of traits occurring in offspring

LE 9-7 F1 genotypes Bb male Formation of sperm Bb female Formation of eggs 1 2 1 2 B b B B B b 1 2 B 1 4 1 4 F2 genotypes 1 2 b B b b b 1 4 1 4

Variations on Mendel’s Laws Mendel’s laws can be applied to all sexually reproducing organisms, but… Some patterns of inheritance don’t follow Mendel’s laws – too complex! Complete vs. Incomplete Dominance Complete dominance: dominant allele exerts its affect regardless of number of copies Incomplete dominance: heterozygote shows intermediate characteristics of two homozygous conditions Not the same as blending Hypercholesterolemia in humans, flower color in snapdragons

LE 9-12a P generation Red RR White rr  Gametes R r F1 generation Pink Sperm 1 2 1 2 R r 1 2 Red RR Pink rR R F2 generation Eggs 1 2 Pink Rr White rr r

LE 9-12b Genotypes: HH Homozygous for ability to make LDL receptors Hh Heterozygous hh Homozygous for inability to make LDL receptors Phenotypes: LDL LDL receptor Cell Normal Mild disease Severe disease

Genes and Multiple Alleles Many genes have more than 2 alleles: multiple alleles Example: ABO blood types in humans: A, B, AB, O Codominance of A and B alleles in heterozygotes phenotype Six possible genotypes in ABO system

LE 9-13 Blood Group (Phenotype) Antibodies Present in Blood Reaction When Blood from Groups Below Is Mixed with Antibodies from Groups at Left Genotypes O A B AB Anti-A Anti-B O ii IAIA or IAi A Anti-B IBIB or IBi B Anti-A AB IAIB

Gene Linkages Inheritance patterns inconsistent with Mendelian laws first noted in 1908 Sweet peas failed to show predicted ratios in the F2 generation Genes located close together on the same chromosome are linked Don’t follow Mendel’s laws of independent assortment Usually inherited together

Not accounted for: purple round and red long Experiment Purple flower PpLl  PpLl Long pollen Observed offspring Prediction (9:3:3:1) Phenotypes Purple long Purple round Red long Red round 284 21 55 215 71 24 Explanation: linked genes Parental diploid cell PpLl P L p l Meiosis Most gametes P L p l Fertilization Sperm P L p l P L P L P L Most offspring P L p l Eggs p l p l p l P L p l 3 purple long : 1 red round Not accounted for: purple round and red long

Crossing Over New combinations of alleles produced from crossing over Occurs during meiosis between homologous chromosomes Results in new combinations of alleles in gametes

Crossing Over T.H. Morgan used fruit flies for genetic studies in early 1900s Easy to grow, short generation time, very inexpensive Studied mutant and “wild-type” phenotypes Was able to determine genes were on chromosomes: chromosome basis of inheritance Didn’t know about crossing over, but something “breaks linkages” according to Morgan Crossover data used to help map genes: determine their relative positions on chromosomes Nucleotide distances used to determine gene maps now

Fruit Flies Offspring Experiment Gray body, long wings (wild type) Black body, vestigial wings  GgLl ggll Female Male Offspring Gray long Black vestigial Gray vestigial Black long 965 944 206 185 Parental phenotypes Recombinant phenotypes Recombination frequency = 391 recombinants 2,300 total offspring = 0.17 or 17% Explanation G L g l GgLl (female) ggll (male) g l g l G L g l G l g L g l Eggs Sperm G L g l G l g L g l g l g l g l Offspring

Drosophila crosses Drosophila melanogaster can be used to study Mendelian patterns of inheritance Many mutant strains available to study Mutations found on various chromosomes Maintained as inbred lines for study Linked and non-linked mutations available Linkages occur on various chromosomes

Sex Linkage Genes unrelated to sex determination, but located on sex chromosomes X-linked in humans Inheritance follows peculiar patterns Eye color in fruit flies: three possible patterns of inheritance

LE 9-23b Female Male XRXR  Xr Y Sperm Xr Y Eggs XR XRXr XRY R = red-eye allele r = white-eye allele

LE 9-23c Female Male XRXr  XRY Sperm XR Y XR XRXR XRY Eggs Xr XrXR

LE 9-23d Female Male XRXr  Xr Y Sperm Xr Y XR XRXr XRY Eggs Xr Xr Xr

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