1. Pre Med III Genetics Guri Tzivion, PhD tzivion@windsor.edu Extension 506 January 2015 Windsor University School of Medicine

2. Pre Med III Genetics Class 2 Genes, Chromosomes and Heredity 1. Intro to genetics: from Mendelian to modern genetics

3. GENETICS: Ancient Greek genetikos, genesis, originAncient Greek The science of heredity and variation in living organismsThe scienceheredityvariation Living organisms inherit traits from their parents beginning from prehistoric times people improved crop plants and animals through selective breeding prehistoric selective breeding Modern genetics basis by Gregor Mendel

4. Chromosome: Greek (chroma, color) and (soma, body): chromosomes strongly stain by particular dyesGreekdyes An organized structure of DNA and protein, found in cellsDNAproteincells Single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequencesgenesregulatory elementsnucleotide sequences In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatinchromatin The complex structure helps a very long DNA molecules to fit into the cell nucleuscell nucleus

5. Gene: The basic unit of heredity in a living organismheredityorganism Contains the information to build and maintain the cells and pass genetic traits to offspringcellstraits In general terms, a gene is a segment of nucleic acid that, taken as a whole, specifies a traitnucleic acid

6. Genome: The full set of chromosomes or genes in a gametechromosomesgamete In diploid organisms, somatic cell contains two full sets of genomes, while gamete cells contain a single setsomatic cell In haploid organisms, including bacteria, viruses, and mitochondria, a cell contains only a single set of the genomehaploidorganismsbacteriavirusesmitochondria Genomics: The study of the genomes of organismsgenomes The entire DNA sequence of organisms and fine-scale genetic mapping effortsDNA sequencegenetic mapping Research of single genes does not fall into the definition of genomics

8. The 46 human chromosomes

9. What is heredity? The passing on of characteristices from parents to offspring. Genetics is the branch of biology that studies heredity the characteristics that are inherited are traits. Mendel was the first person to success in predicting how traits would be transferred from one generation to the next.

10. phenotype The way an organism looks and behaves is called it’s phenotype. Example: what color are your eyes, or your hair? What you see is the phenotype.

11. Genotype Phenotype Activities of genes & gene products Environment & development Genotype = collection of genes (and alleles) in an organism Phenotype = observable properties of an organism Factors contributing to the phenotype

12. Is inheritance blending or particulate? 1.In the mid 19th century, biologists believed that inheritance involved blending of traits, meaning that traits of offspring were the average of their parents. 2.This view was problematic since it suggested that new genetic variations would quickly be diluted and could not be accumulated and passed to subsequent generations as the theory of evolution predicted. 3.The blending theory of inheritance was quickly discredited by Mendel’s experiments, which showed that inheritance is particulate. F1 F2

13. Mendelian Genetics: Gregor Johann Mendel (1822-1884) Augustinian monk, Czech Republic Founding of modern genetics Studied segregation of traits in the garden pea (Pisum sativum) beginning in 1854 Published his theory of inheritance in 1865: “Versuche über Pflanzen-Hybriden” “Experiments in Plant Hybridization” Mendel was “rediscovered” in 1902

14. History: Gregor Mendel (1822–1884) a priest and scientistGregor Mendelpriestscientist Considered the father of genetics for his study in the 1860s of the inheritance of certain traits in pea plantsgeneticsinheritancetraitspea Hypothesized that factors convey traits from parents to offspringHypothesized Spent over 10 years on one experiment Showed that the inheritance of certain traits follow particular lawslaws Mendel's work was not recognized until the turn of the 20th century Didn’t use the term gene, explained results in terms of inherited characteristics Dominant and recessive traits, the distinction between a heterozygote and homozygote, genotype and phenotypeDominantrecessiveheterozygotehomozygotegenotypephenotype

15. Mendel’s Subjects Mendel chose pea plants, which reproduce sexually, meaning that they have two distinct sex cells, male and female. Sex cells are called gametes. Pollination: the transfer of male pollen grains to the pistil of a flower Fertilization: combination of male and female gametes

16. Crosses A hybrid is the offspring of parents that have different forms of a trait, such as tall and short. Mendel first did monohybrid crosses, which means he was looking at only one trait.

17. homozygous vs heterozygous An organism that is homozygous for a trait has two alleles for the trait that are the same. An organism that is heterozygous for a trait has two different alleles (dominant and recessive).

18. Mendel’s Experiments: 1.Used self-fertilization in 34 different garden pea strains (phenotypes). 2.Focused on 7 well-defined traits by crossing one phenotypes at a time. 3.Counted offspring of each phenotype and analyzed the results mathematically.

19. Fig. 11.4, Mendel’s 7 garden pea characters.

20. Some basic terminology: Generations: P = parental generation F 1 = 1st filial generation, progeny of the P generation F 2 = 2nd filial generation, progeny of the F 1 generation (F 3 and so on) Crosses: Monohybrid cross = cross of two different true-breeding strains (homozygotes) that differ in a single trait. Reciprocal cross = sexes for the two strains are reversed (and if the results are the same, trait is not sex-linked). Dihybrid cross = cross of two different true-breeding strains (homozygotes) that differ in two traits. *Genetics etiquette - female conventionally is written first

21. Dominant & recessive alleles (Fig. 11.7):

22. Results of Mendel’s monohybrid parental cross: “Mendel’s Principle of Uniformity in F 1 ” F 1 offspring of a monohybrid cross of true-breeding strains resemble only one of the parents. Why? Smooth seeds (allele S) are completely dominant to wrinkled seeds (allele s). Fig. 11.5

23. Fig. 11.8 Smooth and wrinkled parental seed strains crossed. Punnett square F 1 genotypes 4/4 Ss F 1 phenotypes 4/4 smooth

24. F 1 x F 1 crosses (Fig. 11.6): Mendel also discovered that traits that disappear in the F 1 generation reappear in the F 2 generation in a 1:3 ratio. “Mendel’s Principle of Segregation”

25. F 1 x F 1 Punnett square (Fig. 11.8): F 2 genotypes 1/4 SS 1/2 Ss 1/4 ss F 2 phenotypes 3/4 smooth 1/4 wrinkled

26. Fig. 11.9, Crosses also can be represented with branching diagrams.

27. What about the six other phenotypic traits? 1.Results of reciprocal crosses always were the same. 2.F 1 progeny always resembled the parental strain. 3.In the F 2 progeny, parental strains lost in the F 1 generation always reappeared at a ratio of 1:3. “Mendel’s Principle of Segregation”: Recessive characters masked in the F 1 progeny of two true-breeding strains, reappear in a specific proportion of the F 2 progeny. Modern formulation of Mendel’s Principle of Segregation: Two members of a gene pair segregate (separate) from each other during the formation of gametes.

28. Confirming the Principle of Segregation with test-crosses: SS x SS  true breeding (100% homozygous dominant) ss x ss  true breeding (100% homozygous recessive) How do you determine whether an individual with the dominant phenotype is homozygous or heterozygous? Cross it with homozygous recessive: SS x ss  4/4 dominant trait Ss x ss  1/2 dominant trait + 1/2 recessive trait

29. Fig. 11.11, Test Crosses

30. Mendel’s dihybrid crosses: 1.Mendel also performed crosses involving two pairs of traits, e.g., seed shape (smooth vs. wrinkled) and color (yellow vs. green). 2.If alleles sort independently, four possible phenotypes (2 n ) appear in the F 2 generation in a 9:3:3:1 ratio. “Mendel’s Principle of Independent Assortment”: Alleles for different traits assort independently of one another. Modern formulation of independent assortment: Genes on different chromosomes behave independently in gamete production.

31. Fig. 11.12a Dihybrid cross: F 1 generation

32. Fig. 11.12b Dihybrid cross: F 2 generation Ratio: 9:3:3:1

33. Trihybrid crosses: 1.Involve three independently assorting character pairs. 2.Results: 1.64 combinations of 8 different gametes 2.27 different genotypes 3.8 different phenotypes (2 x 2 x 2) 4.Predicted ratio of phenotypes = 27:9:9:9:3:3:31

34. Summary of Mendel’s 3 Principles:  Mendel’s Principle of Uniformity in F 1 : F 1 offspring of a monohybrid cross of true-breeding strains resemble only one of the parents. Why? Smooth seeds (allele S) are completely dominant to wrinkled seeds (allele s).  Mendel’s Principle of Segregation: Recessive characters masked in the F 1 progeny of two true-breeding strains, reappear in a specific proportion of the F 2 progeny. Two members of a gene pair segregate (separate) from each other during the formation of gametes. Inheritance is particulate, not blending as previously believed.  Mendel’s Principle of Independent Assortment: Alleles for different traits assort independently of one another. Genes on different chromosomes behave independently in gamete production.

35. Mendel’s laws explain inheritance in terms of discrete factors (genes) which are passed from generation to generation according to simple rules of chance. These principles apply to all sexually reproducing organisms for simple patterns of inheritance. Later experiments using many different organisms indicated that more complicated patterns of inheritance exist. These patterns of inheritance include situations where one allele is not completely dominant over another allele, where there are more than two alleles for a trait, or where the genotype does not always dictate the phenotype in a rigid manner

36. Rediscovery of Mendel’s Principles: William Bateson’s (1902) experiments with fowls demonstrated that Mendel’s principles applied also to animals. Bateson argued that mutation (not selection) was the most important force shaping variation in plants and animals. William Bateson also coined the terms: Genetics, Zygote, F 1, F 2 Allelemorph (  allele) 1907 - Reginald Punnett and William Bateson

37. 1905 - Letter from Bateson to Alan Sedgewick