1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-1 Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-2 Chapter 5 Extensions and Exceptions to Mendel’s Laws

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-3 Exceptions to Mendel’s Law Mendel’s traits showed two distinct forms Most genes do not exhibit simple inheritance Genotypic ratios persist but phenotypic ratios may vary because of interactions between –Alleles –Other genes –Non-nuclear genes –Segregation of genes on same chromosome –Environment

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-4 Lethal Alleles Some allele combinations are lethal Figure 5.1b

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-5 Multiple Alleles An individual carries two alleles for each gene A population can have many alleles among the individual members Examples –PKU gene has over 300 alleles resulting in four basic phenotypes –CF gene has over 1000 alleles Genes can mutate in many ways in their DNA sequence

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-6 Incomplete Dominance The heterozygous phenotype is distinct from either homozygous phenotype It may be an intermediate phenotype Figure 5.2

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-7 Codominant Alleles Both alleles are expressed in the heterozygotes Example: The ABO gene encodes a cell surface protein A allele produces A antigen B alleles produce B antigen O allele does not produce antigens A and B antigens may be present on the same cell Alleles A and B are codominant

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-8 Table 5.1

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-9 Codominant Alleles Figure 5.3

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-10 Offspring from Parents with Blood Type A and Blood Type B Figure 5.4

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-11 Epistasis One gene affects the expression of a second gene Example: H gene is epistatic to the ABO gene. H protein attaches a molecule to the cell surface to which the A or B antigens are attached hh genotype = no H protein Without H protein the A or B antigens can not be attached to the cell All hh genotypes have the phenotype of type O, although the ABO blood group can be anything (A, B, AB, or O)

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-12 Incomplete Penetrance The phenotype is not always observed among individuals carrying the genotype – express or not –DD or Dd - only 80% show polydactyly Variable Expressivity A phenotype that varies in intensity  Polydactyly two extra digits on each hand and foot vs. one extra digit on one foot  Individuals with the same genotype for familial hypercholesterolemia have varying levels of symptoms

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-13

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-14 Pleiotropy One gene has many symptoms or controls several functions Example: porphyria variegata Photo © North Wind Picture Archives Figure 5.5a Figure 5.5b

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-15 Genetic Heterogeneity Different genes can produce identical phenotypes  Hearing loss  Osteogenesis imperfecta Genes may encode for different enzymes in a biochemical pathway  Clotting disorders

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-16 Phenocopy Appears inherited but is caused by the environment May have symptoms that resemble an inherited trait or occur within families Examples: Exposure to teratogens –Thalidomide causes limb defects similar to inherited phocomelia –Hydroquinone exposure looks like alkaptonuria Infection –AIDS virus can be passed from mother to child, looking like it is inherited

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-17 Importance of Human Genome Sequence Complications to Mendelian inheritance more common than originally thought Overlapping of definitions – Marfan syndrome has both epistasis and genetic heterogeneity

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-18 Table 5.3

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-19 Mitochondrion Organelle providing cellular energy Contains small circular DNA No crossing over or DNA repair High exposure to free radicals Mutation rate is greater than nuclear DNA 37 genes without noncoding sequences Mitochondrial genes are transmitted from mother to all of her offspring

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-20 Mitochondrial Inheritance Figure 5.8 Figure 5.7

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-21 Table 5.4

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-22 Mitochondrial Disorders Mitochondrial myopathies – weak muscles Leber optic atrophy – impairs vision Ooplasmic transfer technique can enable woman to avoid transmitting a mitochondrial disorder

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-23 Heteroplasmy Many copies of the mitochondrial genome per cell May have more than one allele for the same gene in the same cell Heteroplasmy is the condition where mitochondrial DNA sequence is not the same in all copies

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-24 Linkage Linkage is the transmission of two genes on the same chromosome Two genes on the same chromosome will not assort randomly in meiosis

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-25 Expected Results in a Dihybrid Cross Figure 5.10

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-26 Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross p Ll P L p l Figure 5.10

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-27 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross F1F1 p Ll P L p l

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-28 Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross F1F1 p Ll P L p l Female gametes PLPlpLpl Male gametes PL Pl pL pl Female gametes PLpl Male gametes PL pl

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-29 Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross F1F1 p Ll P L p l Female gametes PLPlpLpl PPLLPPLlPpLLPpLl PPLlPPllPpLlPpll PpLLPpLlppLLppLl PpLlPpllppLlppll Male gametes PL Pl pL pl Female gametes PLpl PPLLPpLl ppll Male gametes PL pl

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-30 Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross F1F1 Phenotypic ratio 3: Self-cross p Ll P L p l Female gametes PLPlpLpl PPLLPPLlPpLLPpLl PPLlPPllPpLlPpll PpLLPpLlppLLppLl PpLlPpllppLlppll Male gametes PL Pl pL pl Female gametes PLpl PPLLPpLl ppll Male gametes PL pl Phenotypic ratio 9:3

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-31 Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross F1F1 Phenotypic ratio 3: Self-cross p Ll P L p l Female gametes PLPlpLpl PPLLPPLlPpLLPpLl PPLlPPllPpLlPpll PpLLPpLlppLLppLl PpLlPpllppLlppll Male gametes PL Pl pL pl Female gametes PLpl PPLLPpLl ppll Male gametes PL pl Phenotypic ratio 9:

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-32 Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross F1F1 Phenotypic ratio 3: Self-cross p Ll P L p l Female gametes PLPlpLpl PPLLPPLlPpLLPpLl PPLlPPllPpLlPpll PpLLPpLlppLLppLl PpLlPpllppLlppll Male gametes PL Pl pL pl Female gametes PLpl PPLLPpLl ppll Male gametes PL pl Phenotypic ratio 9:3:3

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-33 Parents P Genotype PpLl Genes not linked Genotype PpLl Genes linked Self-cross F1F1 Phenotypic ratio 3:1 Self-cross p Ll P L p l Female gametes PLPlpLpl PPLLPPLlPpLLPpLl PPLlPPllPpLlPpll PpLLPpLlppLLppLl PpLlPpllppLl ppll Male gametes PL Pl pL pl Female gametes PLpl PPLLPpLl ppll Male gametes PL pl Phenotypic ratio 9:3:3:1

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-34 Recombination During crossing over in prophase I chromosomes recombine New combinations of alleles are created Parental chromosomes have the original configuration Recombinant chromosomes have new combinations of alleles Figure 5.12

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-35 Crossing over Disrupts Linkage Figure 5.11

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-36 Recombination Frequency of recombination is based on percentage of meiotic divisions that result in breakage of linkage between parental alleles The frequency of recombination between two genes is proportional to the distance between the genes Figure 5.13

37. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-37 Linkage versus Non-linkage Figure 5.14

38. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-38 Linkage Map A linkage map is a diagram indicating the relative distance between genes. 1% recombination = 1 map unit = 1 centiMorgan (cM) Map distances are additive Figure 5.16

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-39 Inheritance of Linked Genes The genes for Rh factor (R) and anemia (E) are linked, but some recombination occurs between the two genes Parent 2 (mother) produces 4% recombinant gametes, therefore the Rh factor gene and the anemia gene are 4 map units or 4 cM apart Figure 5.15

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-40 Linkage Disequilibrium (LD) Is the non-random association between alleles at two locations on a chromosome Example: Two genes, A and B, exist in a population Genes are in equilibrium if the frequency of chromosomes with AB=Ab=aB=ab The genes are in linkage disequilibrium if the frequency of one allele of gene A is seen more frequently with a particular allele of gene B

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-41 LOD Score Is the logarithm of the odds ratio calculated by how often genes and markers are inherited together Is the likelihood that particular crossover frequency data indicates linkage LOD scores of 3 or greater are considered significant and indicate the data would be observed by chance 1/1000 times Was used when disease genes were not identified

42. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-42 Haplotype Is the set of alleles inherited on one chromosome Make it possible to track which parent transmits which genes

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-43 34343434343434343434 12121212121212121212 13131313131313131313 23232323232323232323 14141414141414141414 14141414141414141414 23232424242323242424 23232323232323232323 14141413131414141313 44 33 11 22 Gene A Gene B Gene C Gene D Gene E Mapping with Haplotypes Segregation of a dominant trait is observed in this family (filled symbols). The trait segregates with the yellow haplotype.

44. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 5-44 23232424242323242424 14141413131414141313 13131313131313131313 23232323232323232323 14141414141414141414 34343434343434343434 12121212121212121212 14141414141414141414 23232323232323232323 44 33 11 22 Gene A Gene B Gene C Gene D Gene E Mapping with Haplotypes Recombinant chromosomes III-3 and III-6 inherit recombinant chromosomes. The location of the recombination events indicate that the gene for this trait is located between genes B and D.