1. Exceptions to Mendelian Inheritance Chapter 4

2. Exceptions to Simple Inheritance • Over 15,000 genetically inherited human traits are identified • More that 5,000 are diseases or abnormalities • Many do not follow simple rules of dominance

3. Polygenic Traits • Determined by combined effect of more than one pair of genes. • Sometimes called continuous traits • Examples: • Stature (genes determine size of all body parts) • Human skin, hair and eye color

4. Incomplete Dominance • Results in intermediate expression • Flower color • 4 o’clock flowers • Red, White, Pink • Pitch of human male voice • Lowest and highest are homozygous, intermediate baritones are heterozygous • Tay-Sachs disease • Heterozygous results in 40-60% enzyme production

5. Codominance • Two alleles are both expressed • Longhorn Cattle color • Red, White, Roan (red with white spots) • ABO Blood types: • If both A and B are present, type is AB • Neither is recessive

6. Multiple-Allele Series • More than two choices of alleles are present for a trait • ABO blood type has three alleles • HLA system: genetically inherited system for recognizing and rejecting foreign tissues (transplanted organs) • has the most genes of any other known human multiple-allele series.  (at least 30,000,000 possible HLA genotypes) • HLA stands for "human leukocyte antigen"

7. ABO Blood Types • Mixing blood from two individuals can lead to blood clumping or agglutination • Karl Landsteiner discovered that this was a reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells • he was awarded the Nobel Prize in Physiology or Medicine in 1930

8. What is blood made up of? • The red blood cells • contain hemoglobin. • Red blood cells transport O2 and CO2 to and from body tissues. • The white blood cells • fight infection. • The platelets • help the blood to clot • The plasma • Fluid which contains salts and various kinds of proteins.

9. What determines the different blood groups? • certain protein molecules called antigens and antibodies • Antigens are located on the surface of the red blood cells • Antibodies are in the blood plasma. • Antigens and antibodies clump together (agglutination)

10. What are the different blood groups? • Blood group A (IA, IA ), (IA, i)have A antigens on the surface of red blood cells and B antibodies in blood plasma. • Blood group B (IB, IB ), (IB, i) have B antigens on the surface of red blood cells and A antibodies in blood plasma.

11. What are the different blood groups? • Blood group AB (IA, IB )have both A and B antigens on the surface of red blood cells and no A or B antibodies in blood plasma. • Blood group O (i, i) have neither A or B antigens on the surface of red blood cells but have both A and B antibodies in blood plasma.

12. Blood transfusions – who can receive blood from whom? • The transfusion will work if a person who is going to receive blood has a blood group that doesn't have any antibodies against the donor blood's antigens.

13. People with blood group 0 are called "universal donors" and people with blood group AB are called "universal receivers."

14. Rh Factor • Refers to another antigen on red blood cells • Dominant trait is to have the antigen • Rh+ • Recessive trait is not to have it • Rh- • A person with Rh- blood will produce antibodies to Rh+ blood • Can be a problem in pregnancy

15. Father's Rh factor genes are + + • Mother's are + + • Baby will have one + from the father and one + gene from the mother • Baby will be + + Rh positive.

16. father's genes are + - • mother's are + - • the baby can be: • + + Rh positive • + - Rh positive • - - Rh negative

17. father's Rh factor genes are + + • mother's are - - • the baby will have one + from the father and one - gene from the mother • The baby will be + - Rh positive

20. Mother is given an injection at 28 weeks and after baby is born. • This stops the production of antibodies.

21. Blood Typing

22. X-linked and Sex Related Inheritance

23. Sex chromosomes are not identical homologs • There is a region in common, so they can synapse during meiosis • Y carries some male-specific genes, but lacks many genes that are on the X

24. X-Linkage in Humans (Table 4.3) • Color blindness, deutan and protan types • Ichthyosis • Fabry’s disease • G-6-PD deficiency • Hemophilia A & B • Hunter syndrome • Lesch-nyhan syndrome • Muscular dystrophy

25. Sex-limited Genes • Autosomal genes that are inherited by both male and female BUT • Only expressed in one sex • Examples • Male beard • Milk production in dairy cows • Feathers in domestic fowl

26. Sex-controlled genes • Expressed in both sexes BUT • Different phenotypes for male and female • Example • Pattern baldness

27. Genome Imprinting • Also called genetic imprinting • Affects chromosome region, not individual genes • Some of our genes have to come from a particular parent to work normally • Depends on whether chromosome passes through sperm or egg forming tissue

28. Examples • Inactivation of one X chromosome in females • Prader-Willi syndrome • Functioning gene must come from father • Occurs if part of father’s chromosome 15 is deleted • mental retardation, decreased muscle tone, short stature, emotional fluctuations and an insatiable appetite which can lead to life-threatening obesity

29. Angelman syndrome • Occurs when part of mother’s chromosome 15 is deleted • Severe developmental delay • Behavioral uniqueness such as frequent laughter or smiling, happy demeanor • Movement/Balance Disorder

30. Modifying Genes • Genes that have small quantitative effects on the level of expression of another gene • In mice, coat color is controlled by the B gene. • The B allele = black coat color (dominant) • The b allele = a brown coat (recessive)

31. The intensity of the color, either black or brown is controlled by another gene, the D gene. • dominant D = full color and recessive d = a dilute or faded expression of the color expression at the B gene

32. B_D_ (black) • B_dd (dilute black) • bbD_ (brown) • bbdd (dilute brown)

33. Regulator Genes • Initiate or block other genes • Function in growth and development • Also called homeotic genes

34. Incomplete Penetrance • Effect depends upon certain environmental factors • Nutrition, toxic exposures, other illnesses, actions of other genes • Some individuals do not express the phenotype • E.g. polydactyly • The hand of blues guitar player Hound Dog Taylor exhibiting polydactyly.

35. Pleiotropy • The ability of a single gene to have multiple phenotypic effects • e.g., sickle cell anemia causes multiple symptoms, only one of which is the actual sickle celled condition

36. Pleiotropy • Porphyria variegata: dominant metabolic disorder • Affects urinary, digestive, muscular and nervous systems • Seen in King George III of England

37. Epistasis • A condition in which a gene at one locus can effect the phenotypic expression of a second gene • Causes deviation from the predicted 9:3:3:1 Mendelian ratio (often 9:7)

38. For example, in mice, fur color controlled by two genes - C (melanin deposition, and B (Black versus brown)

39. Stuttering Alleles • Found in more than 15 human disorders • Results in “anticipation”: worsening of symptoms with each generation • Repeats of <40 copies occur normally in genes and introns (CAGCAGCAGCAG) • Larger repeats unstable, increasing in number in each generation • May make mRNA too large to get out of nucleus

40. Human Repeat Disorders

41. Environmental Influences • Sometimes difficult to determine whether individual differences in a trait are caused by genes or environment • Type I Diabetes • Runs in families in no particular pattern • Immune system attacks pancreas • Connected to severe pancreatic infection • Inherit a susceptibility, do not develop diabetes unless infection occurs

42. Heart Health • Genes control: • How well body handles lipids in blood • Blood pressure • Blood clotting • We control: • Diet • Smoking • Cholesterol levels • Amount of exercise • Obesity • stress