More Genetics!

1. More Genetics! Extensions: Going beyond Mendel…

2. Sex-Linked Trait • Genes on autosomes are autosomally linked. • If a gene is found only on the X chromosome and not the Y chromosome, it is a sex-linked or X-linked trait. • Because the gene controlling the trait is located on the sex chromosome, sex linkage is linked to the gender of the individual. • Usually such genes are found on the X chromosome. The Y chromosome is thus missing such genes. • Females will have two copies of the sex-linked gene while males will only have one copy of this gene. • If gene is recessive: • males only need one recessive gene to have a sex-linked trait This is why males exhibit some traits more frequently than females.

3. Sex-Linked Traits (X-linked Traits) • The chromosomes that determine gender. • Males XY (monozygous) • Females XX (typical dominant/recessive) • Because the X chromosome contains many more genes than the Y chromosome, males are more likely to express any mistake that may be on the X chromosome. • Red-green color blindness • Hemophilia • Duchenne muscular dystrophy Sex-Linked

4. Drosophila Chromosomes Sex-Linked

5. 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: Sex-Linked

6. Sex-Linked

7. Red-Green Color Blindness • Color vision In humans: • Depends 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 in X-linked genes cause RG color blindness: • All males with mutation (XbY) are colorblind • Only homozygous mutant females (XbXb) are colorblind • Heterozygous females (XBXb) are asymptomatic carriers Sex-Linked

8. Red-Green Colorblindness Chart Sex-Linked

9. X-Linked Recessive Pedigree Sex-Linked

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

11. Hemophilia • “Bleeder’s Disease” • Blood of affected person either refuses to 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 Sex-Linked

12. Sex-Linked

13. Fragile X Syndrome • Due to base-triplet repeats in a gene on the X chromosome • CGG repeated many times • 6-50 repeats – asymptomatic • 230-2,000 repeats – growth distortions and mental retardation • Inheritance pattern is complex and unpredictable Sex-Linked

14. Incomplete Dominance • The phenotype of a heterozygote (CRCW) is intermediate between the phenotypes of the two types of homozygotes (CRCR and CWCW). In incomplete dominance there will be three phenotypes, one for each possible combination, not two as in a typical dominant/recessive situation!

15. Incomplete Dominance Example of incomplete dominance: Snapdragons! Incomplete Dominance

16. Figure 11.14 Incomplete Dominance

17. Assessment of dominance depends on the level of analysis! A heterozygote may display a dominant phenotype at the organismal level, but at a biochemical level may show incomplete dominance. Tay-Sachs disease: caused by absence of an enzyme, hexosaminidase A (Hex-A) Incomplete Dominance Homozygous dominant: normal levels of Hex-A, normal development of child Homozygous recessive: no Hex-A, death of child by age 5 Heterozygote:1/2 normal levels of Hex-A, normal development of child

18. Assessment of dominance depends on the level of analysis! Survival die live Complete Dominance HexA+/ HexA+ HexA+/ HexA- HexA-/ HexA- Tay-Sachs Incomplete Dominance Amount of hexaminidase die live Incomplete Dominance HexA-/ HexA- HexA+/ HexA+ HexA+/ HexA- Tay-Sachs HexA- codes for a nonfunctional enzyme.

19. Co-Dominance • Phenotypes caused by each allele are both seen when both alleles are present. • Ex. Blood Type (also shows multiple alleles) • Sickle Cell Anemia

20. Sickle cell anemia http://www.netwellness.org/ency/imagepages/1223.htm Sickle Cell Anemia • RBCs sickle shaped • Anemia • Pain • Stroke • Leg ulcers • Jaundice • Gall stones • Spleen, kidney & lungs Co- Dominance

21. Sickle Cell Anemia • Normal red blood cells • contain hemoglobin A • are soft and round and can squeeze through tiny blood tubes (vessels) • live for about 120 days before new ones replace them • Hemoglobin S red blood cells (different form of hemoglobin A) • do not live as long as normal red blood cells (normally about 16 days) • become stiff, distorted in shape and have difficulty passing through the body’s small blood vessels. • When sickle-shaped cells block small blood vessels, less blood can reach that part of the body. Tissue that does not receive a normal blood flow eventually becomes damaged. This is what causes the complications of sickle cell disease. • Normal hemoglobin: AA • Sickle Cell Trait: AS • Sickle Cell trait (AS) both hemoglobin A and S are produced in the red blood cells. People with sickle cell trait are generally healthy. • Sickle Cell Disease: SS Co- Dominance

22. Multiple Alleles • Genes with more than two alleles in the population • any individual possesses only two such alleles (at equivalent loci on homologous chromosomes.) • Alleles for Blood Type (A, B, O) • Human-Leukocyte-Associated antigen (HLA) • HLA genes code for protein antigens that are expressed in most human cell types and play an important role in immune responses. These antigens are also the main class of molecule responsible for organ rejections following transplantations—thus their alternative name: major histocompatibility complex (MHC) genes. • There are over 100 alleles for HLA!

23. Human ABO Blood Groups • Gene “I” specifies which sugar is found on the outside of red blood cells • 3 alleles are present in the human population: • IA = N-acetyl-galactosamine • IB = galactose • i (also referred to as o) = no sugar present • This gives us 6 possible genotypes Multiple Alleles

24. The Human ABO Blood Group System Multiple Alleles

25. Multiple Alleles

26. Immunology 101 • (In a nutshell) • Sugar on the blood cell is an antigen* (A, B, A and B, or none) • Your immune system thinks your own antigens are fine • Your immune system makes antibodies against non-self antigens • Antibodies recognize and target cells with antigens for destruction Multiple Alleles *something that elicits an immune response

27. Multiple Alleles

28. There are 3 different alleles, IA, IB, and i • Allele IA makes a cell surface antigen, symbolized with a triangle • IB makes a different antigen, symbolized as a circle • i makes no antigen Multiple Alleles

29. A little more scientific in perspective… Multiple Alleles

30. Multiple Alleles: ABO Blood Type A medical problem - some blood transfusions produce lethal clumping of cells. The antigens (A and B) cause antibodies to be produced on by individuals who do not have them! Type A blood transfused into Type B person- not OK! Type B blood transfused into Type B person – OK!

31. Multiple Alleles

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 Polygenic Interitance

33. additive effects (essentially, incomplete dominance) of multiple genes on a single trait (phenotypic appearance) AA = dark Aa = less dark aa - light Think of each “capital” allele (A, B, C) as adding a dose of brown paint to white paint. Polygenic Interitance

34. Polygenic Interitance

35. Each dominant allele contributes a small but equal effect to the phenotype. Polygenic Interitance

36. By the way… • The genetics of human eye color is actually complicated and is not dictated solely by the simple dominant-recessive actions of two alleles of one gene. There are multiple genes (with multiple alleles of each gene) involved, and the interactions of these genes have not been clearly elucidated (understood/explained). • This is clearly evidenced by the enormous variation in human eye color that does not always follow the simplified model. People generally have flecks, rays and “splotches” of browns, blues, ambers and greens that overlay the background color.

37. Inheritance of Eye Color in Humans • The inheritance of brown or blue eyes in humans is a result of two copies of a gene that codes for pigment production. • There are four alleles for eye pigmentation, two that code to produce pigment and two that code for "no pigment". • We have an increase in variation within the population because the heterozygotes phenotypes of the genes involved are expressed (codominance). • The eye color alleles code for the production of a yellow-brown pigment* • *There is also a yellow overlay gene which, when combined with the basic pigment gene, alters light brown to hazel and light blue to green.

38. First Iris LayerPigment • AA = Produce lots of pigment • Aa = Produce some pigment • aa = Do not produce pigment Second Iris Layer Pigment • BB = Produce lots of pigment • Bb = Produce some pigment • bb = Do not produce pigment Eye Color

39. What does this tell you about the inheritance of height?

40. Birds of a Feather? Polygenic Interitance

41. From the Greek words meaning “many” and “influences” A single gene influences more than one characteristic Mendel also recognized this effect. He observed that pea plants with red flowers had red coloration where the leaf joined the stem, but that their seed coats were gray in color. Plants with white flowers had no coloration at the leaf-stem juncture and displayed white seed coats. These combinations were always found together, leading Mendel to conclude that they were likely controlled by the same hereditary unit (i.e., gene). Pleiotropy

42. The albino condition lack pigment in their skin and hair Affects eye and skin sensitivity to light in many animals Also have crossed eyes at a higher frequency than pigmented individuals. This occurs because the gene that causes albinism can also cause defects in the nerve connections between the eyes and the brain. These two traits are not always linked, again showing the complexity of genetic interactions in determining phenotypes. Pleiotropy

43. A Comparison

44. Epistasis • Genes whose actions are required for other genes to be expressed. • This has an effect on mammalian hair color. The dominant allele of this gene allows pigment to be produced, while the recessive allele does not. A second gene controls the distribution of the pigment in the hair. •  Example: Coat color in Labrador Retrievers • BB or Bb-----------> Black • bb-------------------->Chocolate • Where do Yellow Labs come from? • Yellow vs. Dark (Black or Chocolate) is controlled by the Extension Gene (E) • EE or Ee--------->dark color • ee------------------>yellow (regardless of BB or bb)

45. Practice Problem… • BbEe X BbEe • Set up this cross and determine the ratios of the offspring Epistasis

46. Mice also have black or brown-pigmented fur depending on the inheritance of a gene for pigmentation. A second, independent gene prevents the distribution of any pigment in the fur. This gene, when recessive, results in white mice. Epistasis

47. In horses, brown coat color (B) is dominant over tan (b). Gene expression is dependent on a second gene that controls the deposition of pigment in hair. The dominant gene (C) codes for the presence of pigment in hair, whereas the recessive gene (c) codes for the absence of pigment. If a horse is homozygous recessive for the second gene (cc), it will have a white coat regardless of the genetically programmed coat color (B gene) because pigment is not deposited in the hair. Epistasis

48. Even the environment has an impact on some genes! Environmental effects • environment often influences phenotype • the norm of reaction = phenotypic range due to environmental effects • norms of reactions are often broadest for polygenic characters. • Flower color in hydrangia determined by pH of soil! • Blue hydrangia require acidic pH • Pink hydrangia require basic pH

49. Temperature can affect gene expression! Environmental Influences

50. Let’s Experiment • The classic study on environmental control of gene expression was done with the pigmentation gene of Siamese cats and Himalayan cats and rabbits. • Typically, the animal's extremities are pigmented while the body core remains unpigmented or cream colored. • The pigmentation gene is activated when the temperature falls below a certain point. • To demonstrate that the pattern was temperature controlled, the backs of rabbits were shaved and ice packs placed on the shaved portion. • When new fur grew, it was pigmented. Environmental Influences