Transmission Genetics: Heritage from Mendel

1. 2 Transmission Genetics: Heritage from Mendel

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 crossesproduce 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 ofSegregation (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,1/2recessive 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 phenotypicratio (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