Outline

1. Mendelian Inheritance

2. Outline • Blending Inheritance • Monohybrid Cross • Law of Segregation • Modern Genetics • Genotype vs. Phenotype • Punnett Square • Dihybrid Cross • Law of Independent Assortment • Human Genetic Disorders

3. Gregor Mendel

4. Gregor Mendel • Austrian • Monk : entered the Saint Augustine order but clashed with the senior priests • Tried the teaching profession but failed the state exam twice (actually withdrew 2nd time) • sent to the University of Vienna, then returned to the monastery in Brunn where he taught part time and amused himself counting peas and flowers of over 30,000 pea plants for 10 year between 1856-1866. • Formulated fundamental laws of heredity in early 1860s(published 1866, Darwin published 7 years earlier, 1859) • Had no knowledge of cells or chromosomes • Did not have a microscope

5. Fruit and Flower of theGarden Pea All peas are yellow when one parent produces yellow peas and the other produces green peas (Yy) (yellow is dominant)

6. True breeding, monohybrid garden pea traits studied by Mendel F2 results (TT) (tt) (I I) (i i) 3 : 1

7. Blending Inheritance • Theories of inheritance in Mendel’s time: • Based on blending • Parents of contrasting appearance produce offspring of intermediate appearance • Mendel’s findings were in contrast with this • He formulated the particulate theory of inheritance • Inheritance involves reshuffling of discreet elements (genes) from generation to generation

8. One-Trait Inheritance • Mendel’s cross-breeding experiments • Used homozygous “true-breeding” plants (either (G,G) or (g,g). • Chose monohybrid varieties (differed in only one trait, i.e, Tall verses short) • Performed reciprocal crosses • Crossed the Parental generation = P, to give… • First filial generation offspring = F1 • Crossed F1 to give second filial generation offspring = F2 • Formulated the Law of Segregation

9. Mendel’s Monohybrid Crosses:An Example

10. Mendel observed that: • Each individual has a pair of factors for each trait • The factors segregate (separate) during gamete (sperm & egg) formation • Each gamete contains only one factor from each pair • Fertilization gives the offspring two factors for each trait

11. We now know that : • The two factors (are genes) that separate (as maternal or paternal alleles) during gamete formation (when homologues separate at anaphase of meiosis-1) and each gamete contains only one factor from the pair (because meiosis results in reductive division that produces haploid cells). Fertilization give the offspring two factors (creating a diploid zygote, 2n). • (yellow type = Mendellian terminology; green type = modern biology)

12. Modern Genetics View • Each trait in a pea plant is controlled by two alleles (alternate forms of a gene) • Dominant allele (capital letter) masks the expression of the recessive allele (lower-case) • Alleles occur on a homologous pair of chromosomes at a particular gene locus • Homozygous = identical alleles • Heterozygous = different alleles

13. Homologous Chromosomes This chromosome is homozygous / heterozygous at all loci.

14. Genotype Versus Phenotype • Genotype (The underlying genetic make-up for a trait) • Refers to the two alleles an individual has for a specific trait • If identical, genotype is homozygous • If different, genotype is heterozygous • Phenotype • Refers to the physical appearance of the individual

15. Punnett Square • Table listing all possible genotypes resulting from a cross • All possible sperm genotypes are lined up on one side (recall, these are haploid = one allele only) • All possible egg genotypes are lined up on the other side (recall, these are haploid = one allele only) Every possible zygote genotypes are placed within the squares

16. Punnett Square ShowingEarlobe Inheritance Patterns With this phenotype, how can we determine the underlying genotype? (i.e. it could be either (EE) homozygous or (Ee) heterozygous)

17. A Tests-cross is used to determine underlying genetics (genotype) • (i.e. whether the individual is homozygous or heterozygous) • Cross the unknown individual with a “true-breeding” (homozygous) recessive (e e) .

18. Dihybrid Cross (two-traits)

19. Mendel’s Dihybrid crosses: • Dihybrid cross uses true-breeding plants differing in two traits • Observed phenotypes among F2 plants • Formulated Law of Independent Assortment • The pair of factors for one trait segregate independently of the factors for other traits • All possible combinations of factors can occur in the gametes

20. Two-Trait Test Cross

21. Human Genetic Disorders • Autosome - Any chromosome other than a sex chromosome • Autosomal disorders :Genetic disorders caused by genes on autosomes • Some genetic disorders are autosomal dominant • An individual with AA has the disorder • An individual with Aa has the disorder • An individual with aa does NOT have disorder • Other genetic disorders are autosomal recessive • An individual with AA does NOT have disorder • An individual with Aa does NOT have disorder, but is a carrier • An individual with aa DOES have the disorder Which type (autosomal dominant or autosomal recessive is more likely to be passed on to offspring? Homework Assigment ! Only need one dominant allele to develop the disease. Must have both recessive alleles to develop the disease.

22. Autosomal Recessive Pedigree Chart Aa

23. Autosomal Dominant Pedigree Chart

24. Autosomal Recessive Disorders • Tay-Sachs Disease • Progressive deterioration of psychomotor functions • Cystic Fibrosis • Mucus in bronchial tubes and pancreatic ducts is particularly thick and viscous • Phenylketonuria (PKU) • Lack enzyme for normal metabolism of phenylalanine

25. Cystic Fibrosis Therapy

26. Autosomal Dominant Disorders • Neurofibromatosis • Tan or dark spots develop on skin and darken • Small, benign tumors may arise from fibrous nerve coverings • Huntington Disease • Neurological disorder • Progressive degeneration of brain cells • Severe muscle spasms • Personality disorders

27. A Victim of Huntington Disease

28. Incomplete Dominance • Heterozygote has phenotype intermediate between that of either homozygote • Homozygous red has red phenotype • Homozygous white has white phenotype • Heterozygote has pink (intermediate) phenotype • Phenotype reveals genotype without test cross

29. Incomplete Dominance

30. Multiple Allelic Traits • Some traits controlled by multiple alleles • The gene exists in several allelic forms (but each individual only has two) • ABO blood types • The alleles: • IA = A antigen on red cells, anti-B antibody in plasma • IB = B antigen on red cells, anti-A antibody in plasma • i = Neither A nor B antigens, both antibodies

31. Inheritance of Blood Type Mother has IgM antibodies against B-antigens, this may mature to IgG antibodies and result in heamolytic disease in subsequent pregnancies.

32. Polygenic Inheritance • Occurs when a trait is governed by two or more genes having different alleles • Each dominant allele has a quantitative effect on the phenotype • These effects are additive • Result in continuous variation of phenotypes

33. Height in Human Beings

34. Frequency Distributions inPolygenic Inheritance

35. Terminology • Pleiotropy • A gene that affects more than one characteristic of an individual • Sickle-cell (incomplete dominance) • Codominance • More than one allele is fully expressed • ABO blood type (multiple allelic traits) • Epistasis • A gene at one locus interferes with the expression of a gene at a different locus • Human skin color (polygenic inheritance)

36. Environment and Phenotype:Himalayan Rabbits

37. Other patterns of inheritance . • Not all genes follow Mendelian patterns of inheritance, i.e. all genes do not segregate and sort independently! • What feature allows two genes to segregate and sort independently of each other ?

38. Chromosomal Inheritance • Humans are diploid (2 chromosomes of each type) • The sex chromosomes: • One of the chromosome pairs determines the sex of an individual • Autosomes: • The other 22 pairs of chromosomes. • Autosomal chromosomes are numbered from largest (#1) to smallest (#22) • The sex chromosomes are numbered as the 23rd pair

39. Human Karyotype

40. Sex in Humans isDetermination in Humans by Sperm. • Sex is determined in humans by allocation of chromosomes at fertilization • Both sperm and egg carry one of each of the 22 autosomes • The egg always carries the X chromosome as number 23 • The sperm may carry either and X or Y • If the sperm donates an X in fertilization, the zygote will be female • If the sperm donates a Y in fertilization, the zygote will be male • Therefore, the sex of all humans is determined by the sperm donated by their father Henry the eighth went through six wives because they could not produce a male heir to the throne. Knowing what you now know, what could Anne Boleyn have said to King Henry in order to save her head?

41. X-Linked Alleles • Genes carried on autosomes are said to be autosomally linked • Genes carried on the female sex chromosome (X) are said to be X-linked (or sex-linked) • X-linked genes have a different pattern of inheritance than autosomal genes have • The Y chromosome is blank for these genes • Recessive alleles on X chromosome: • Follow familiar dominant/recessive rules in females (XX) • Are always expressed in males (XY), whether dominant or recessive • Males said to be monozygous for X-linked genes

42. Sex linked traits. Example: eye Color in Fruit Flies • Fruit flies (Drosophila melanogaster) are common subjects for genetics research • They normally (wild-type) have red eyes • A mutant recessive allele of a gene on the X chromosome can cause white eyes • Possible combinations of genotype and phenotype:

43. X-Linked Inheritance Notice that for true-breeding monohybrid crosses the F1 generation only produces one offspring genotype, so full Punnett Squares are not done.

44. Human X-Linked Disorders:1. Red-Green Color Blindness • Color vision In humans: • Depends on three different classes of cone cells in the retina • Only one type of pigment is present in each class of cone cell • The gene for blue-sensitive is autosomal • The red-sensitive and green-sensitive genes are on the X chromosome • Mutations at this locus in X-linked genes cause RG color blindness: • All males with mutation (XbY) are colorblind • Heterozygous females (XBXb) are asymptomatic carriers • Only homozygous mutant females (XbXb) are colorblind

45. X – linked disorders • Three types of cones • Red • Blue • Green

46. Red-Green Colorblindness Chart

47. X-Linked Recessive Pedigree All sons will be color-blind.

48. Human X-linked disorders: 2. Muscular Dystrophy Muscle cell

49. Human X-Linked Disorders:Muscular Dystrophy • Muscle cells operate by release and rapid sequestering of calcium • A Protein (dystrophin) is required to keep calcium sequestered • Dystrophin production depends on X-linked gene. • A defective allele (recessive) causes absence of dystrophin • Allows calcium to leak into muscle cells • Causes muscular dystrophy • All sufferers of Dushenne’s muscular dystrophy are male • Defective gene always unopposed in males (XdY) • Males die before fathering potentially homozygous recessive daughters

50. Human X-Linked Disorders:3. Hemophilia • “Bleeder’s Disease” • Blood of affected person either does not clot or clots too slowly • Hemophilia A – due to lack of clotting factor IX • Hemophilia B – due to lack of clotting factor VIII • Most victims male, receiving the defective allele from carrier mother • Bleed to death from simple bruises, etc. • Factor VIII now available via biotechnology