1. Transmission Genetics: Heritage from Mendel 2

2. Mendel’s Genetics Experimental tool: garden pea Outcome of genetic cross is independent of whether the genetic trait comes from the male or female parent Reciprocal genetic crosses produce the same results Many human traits follow this pattern of inheritance

4. Mendel’s Experiments Gene : inherited trait Plants with different forms of a trait, such as yellow vs. green seeds (alleles) were genetically crossed Mendel counted the number of offspring with each trait (F1), (e.g.: green seeds) He crossed F1 plants among themselves and counted F2 offspring

6. Mendel’s Observation Genetic cross between parents that “breed true” for a pair of traits, round seeds vs. wrinkled seeds, produces offspring with round seeds only (F1) Round seeds are dominant Each parent has two identical copies of the genetic information specifying the trait (homozygous) and contributes one in each cross (P1)

7. Mendel’s Hypothesis Round seed parent “AA” = genotype Wrinkled seed parent “aa” = genotype Round seed parent contributes “A” gamete to offspring Wrinkled seed parent contributes “a” gamete to offspring

9. Law of Dominance Offspring genotype = A + a = Aa heterozygous All offspring produce round seeds although they are genetic composites of “Aa” because “A” (round) is dominant to “a” (wrinkled)

10. Law of Segregation F1 genotype =“Aa”= monohybrid “Aa” parent produces either “A” or “a” gametes in equal proportion Law of Segregation ( simple consequence of two chromosomes)

11. Monohybrid Genetic Cross Genetic cross : Aa X Aa produces A and a gametes from each parent Punnett square shows four possible outcomes = AA Aa, aA, and aa Three combinations = AA, Aa, and aA produce plants with round seeds and display a round phenotype Fourth combination = aa displays wrinkled phenotype = recessive

13. Monohybrid Genetic Cross

14. Mendelian Ratios Genotypic ratios differ from phenotypic ratios since dominant phenotype consists of AA” and “Aa” F2 results of monohybrid cross show 3:1 round:wrinkled phenotypic ratio Genotypic ratios of monohybrid cross are 1:2:1 = 1/4 AA + 1/2 Aa + 1/4 aa

15. Testcross Analysis Testcross analysis allows geneticist to determine whether observed dominant phenotype is associated with a homozygous “AA” or heterozygous “Aa” genotype Genetic cross is performed using a recessive testcross parent = “aa”

16. Testcross Results AA + aa = Aa ; dominants only parent homozygous Aa + aa = 1/2 Aa + 1/2 aa produces 1/2 dominant, 1/2 recessive parent heterozygous

18. Dihybrid Cross Ratios two different phenotypic traits, such as seed color (yellow vs. green) and seed shape (round vs. wrinkled) Analysis of all combinations: (3:1 round : wrinkled and 3:1 yellow : green) produces 9:3:3:1 phenotypic ratio (round/yellow : round/green : wrinkled/yellow : wrinkled/green

21. Dihybrid F2

22. Law of Independent Assortment Combinations of individual elements within dihybrid pair generate genotypic ratios for dihybrid cross True for any number of unlinked genes Also a consequence of distinct chromosomes

24. Dihybrid Testcross WwGg gametes = WG + wG +Wg + wg = 1:1:1:1 ratio; double recessive gametes = wg Offspring = WwGg + wwGg + Wwgg + wwgg = 1:1:1:1 ratio Testcross shows that parent is heterozygous for both traits (dihybrid)

26. Trihybrid Genetic Cross Trihybrid cross = three pairs of elements that assort independently, such as WwGgPp For any pair phenotypic ratio = 3:1 For two pairs ratio = 9:3:3:1 Trihybrid: 27:9:9:9:3:3:3:1

27. Probability Rules Addition Rule: The probability of obtaining one or the other of two mutually exclusive events is the sum of their individual probabilities Multiplication Rule: The probability of two independent events occurring simultaneously equals the product of their individual probabilities

28. Mendelian Probabilities Dihybrid crosses also follow sum rule and product rule to determine outcome probabilities Phenotypic outcome = 9:3:3:1 Genotypic outcome = 1:2:1:2:4:2:1:2:1

29. Pedigree Analysis In humans, pedigree analysis is used to determine individual genotypes and to predict the mode of transmission of single gene traits To construct a pedigree, the pattern of transmission of a phenotypic trait among individuals in a family is used to determine whether the mode of inheritance is dominant or recessive Pedigree analysis is used to study single gene disorders, such as Huntington’s Disease, a progressive neurodegenerative disorder

31. Pedigree Analysis: Dominance Dominant phenotypic traits usually appear in every generation of a pedigree About 1/2 the offspring of an affected individual are affected The trait appears in both sexes if the gene is not on the X chromosome

33. Dominant Single Gene Disorders

34. Pedigree Analysis: Recessive Pedigree analysis can used to distinguish dominant vs. recessive modes of inheritance for traits determined by single genes Analysis of patterns of transmission of recessive genes is used to identify carriers of recessive traits which cannot be determined by direct phenotypic analysis Recessive traits occur in individuals whose parents are phenotypically dominant

35. Inheritance of Recessive Genes Two phenotypically dominant people who produce a child with a recessive genetic disorder: 1/4 probability that any of their children will be affected and 1/2 that they will be carriers

37. Recessive Genetic Disorders

38. Incomplete Dominance Heterozygote phenotype is intermediate between dominant and recessive phenotypes (snapdragons) F1 of cross between dominant (red) and recessive (ivory) plants shows intermediate phenotype (pink) F2 products show identical phenotypic and genotypic ratios

40. Multiple Alleles/Co-dominance For some traits more than two alleles exist in the human population ABO blood groups are specified by three alleles which specify four blood types ABO blood group inheritance also illustrates principle of co-dominance in which both alleles contribute to the phenotype in the heterozygote Antibodies are proteins which bind to stimulating molecules = antigens

41. Multiple Alleles/Co-dominance IA and IB are dominant to IO, genotype AIO = type A; IBIO = type B IA and IB are co-dominant; each allele specifies antigen: genotype IAIB = type AB IO = is recessive genotype IOIO

43. Biochemical Genetics Many recessive genes code for enzymes which carry out specific steps in biochemical pathways Mutations which alter the structure of genes block enzyme production if both copies of the gene are defective Disorders were termed “inborn errors of metabolism” by Garrod

44. Biochemical Genetics Recessive genes often contain mutations which block the formation of gene product (ww) Heterozygotes which contain one recessive gene copy (Ww) may produce only 1/2 the amount of protein specified by the homozygous dominant (WW) which contains two functional copies of the gene

46. Biochemical Genetics Heterozygotes (Ww) may still produce sufficient gene product to display dominant phenotype = round seed; genotype = carrier For some genes reduction of gene product by 1/2 in the heterozygote may be physiologically significant, especially for structural proteins = dominant disorders

47. Biochemical Genetics Variable expressivity refers to genes that are expressed to different degrees in different individuals, e.g.: severity of an inherited disease Incomplete penetrance means that the phenotype predicted from a specific genotype is not always expressed, e.g.: individual inherits mutant gene but shows no effect

48. Genetic Epistasis Epistasis alters Mendelian 9:3:3:1 phenotypic ratios in dihybrid inheritance In epistasis, two sets of genetic elements interact to produce a single phenotype, which modifies the observed phenotypic ratios Mendelian pattern of inheritance

51. Genetic Complementation Complementation tests are used to determine if different phenotypes result from variations in one gene Homozygous recessive genotypes which are genetically crossed can only produce a dominant phenotype if the recessive genetic elements are located on different genes

53. Genetic Complementation A mutant screen is an experiment which generates mutations which affect specific phenotypes Multiple alleles refer to the various forms of a gene Wildtype refers to the phenotype for a specific trait most commonly observed

54. Genetic Complementation The complementation test groups mutants into allelic classes called complementation groups Lack of complementation = two mutants are alleles of the same gene Principle of Complementation: two recessive allelic mutations produce mutant phenotype; two non-allelic recessive mutations show no effect