Understanding Gene Transmission: Mendel's Laws and Human Genetics

1. How Genes Are Transmitted from Generation to Generation Chapter 4

2. Central Points • Genes are transmitted from generation to generation • Traits are inherited according to predictable rules

3. Gregor Mendel – The Father of Genetics

4. 4.1 How Are Genes Transmitted? • Experiments with pea plants in 1800s • Traits,distinguishing characteristics • Specific patterns in the way traits were passed from parent to offspring

5. Different Plant Heights

6. Mendel’s Experiments • Some traits disappeared in the first generation of offspring (all tall) • Reappeared in 3:1 ratio (tall:short) • Dominant traitpresent in the first-generation offspring (tall) • Recessive trait absent in first generation but reappeared in the next generation (short)

7. Traits Are Passed by Genes • “Factors” or genes transmitted from parent to offspring • Each parent carries a pair of genes for a trait but contributes only one gene to each offspring • Separation of gene pair occurs during meiosis

8. Genes • Alleles: variations of a gene • Geneticists use letters for each allele. • Homozygous: identical alleles of a gene • TT or tt • Heterozygous: nonidenticalalleles • Tt

9. Phenotype and Genotype • Phenotype: what an organism looks like • tall or short • Genotype: genetic makeup • TT, Tt, and tt • Identical phenotypes may have different genotypes • TT or Tt have tall phenotype

10. Mendel’s Law of Segregation • Two copies of each gene separate during meiosis • One copy of each gene in the sperm or egg • Each parent gives one copy of each gene

11. Sorting of Alleles

12. Mendel’s Law of Independent Assortment • Members of a gene pair segregate into gametes independently of other gene pairs • Gametes can have different combinations of parental genes

13. Human Traits: Albinism • Pigmentation dominant and lack of pigment recessive • AA, Aa: Pigmented • aa: Albino • Both parents Aa, each child has 25% chance of being albino (3:1 ratio)

14. Aa Aa × Aa Aa a a A A Two carriers of albinism have a child. The male and female can contribute either an A allele or an a allele to the gamete. Fig. 4-3a, p. 61

15. Genotype Phenotype A a 1 AA AA normal Aa normal 3/4 normal coloring A 2 Aa Aa normal aa albino a 1/4 albino 1 aa This shows the possible genotypes and phenotypes of the offspring. The possible offspring and allele combinations are shown above. Fig. 4-3b, p. 61

16. Pedigree 1 • Shows all family members and identifies those affected with the genetic disorder

17. Pedigree 2

18. Pedigree Symbols

19. Male Female Mating Mating between relatives (consanguinous) I Parents and children. Roman numerals symbolize generations. Arabic numbers symbolize birth order within generation (boy, girl, boy) II 1 2 3 I, II, III, etc. = each generation 1, 2, 3, etc. = individuals within a generation p. 62

20. or Unaffected individual or Affected individual or Known heterozygotes or Proband; a person in family who is the focus of the pedigree P P I, II, III, etc. = each generation 1, 2, 3, etc. = individuals within a generation p. 62

21. Pedigree Symbols

22. Proband • Person who is the focus of the pedigree • Indicated by an arrow and the letter P

23. 4.2 Examining Human Pedigrees • Determine trait has dominant or recessive inheritance pattern • Predict genetic risk for: • Pregnancy outcome • Adult-onset disorder • In future offspring

24. Three Possible Patterns of Inheritance • Autosomal recessive • Autosomal dominant • X-linked recessive • Autosomal on chromosomes 1–22 • X-linked traits on the X chromosome

25. Autosomal Recessive • Unaffected parents can have affected children • All children of affected parents are affected • Both parents Aa, risk of affected child is 25% • ~Equal affected male and female • Both parents must transmit the gene for a child to be affected

26. Autosomal Recessive Pedigree

27. Autosomal Recessive Genetic Disorders

28. Albinism • A = normal coloring; a = albinism • Group of genetic conditions, lack of pigmentation (melanin) in the skin, hair, and/or eyes • Normally, melanin in pigment granules inside melanocytes • In albinism, melanocytes present but cannot make melanin • Oculocutaneous albinism type I (OCA1)

29. Cystic Fibrosis (CF) • C = normal; c = cystic fibrosis • CF affects glands that produce mucus and digestive enzyme • CF causes production of thick mucus in lungs blocks airways • Develop obstructive lung diseases and infections • Identified CF gene and protein (CFTR)

30. Sickle Cell Anemia (SCA) • S = normal red blood cells; s = sickle • High frequency in areas of West Africa, Mediterranean Sea, India • Abnormal hemoglobin molecules aggregate to form rods • Red blood cells, crescent- or sickle-shaped, fragile and break open

31. Normal and Sickled Cells

32. Autosomal Dominant (1) • Requires one copy of the allele (Aa) rarely present in a homozygous condition (AA) • aa: Unaffected individuals • Affected individual has at least one affected parent • Aa X aa: Each child has 50% chance of being affected

33. Autosomal Dominant (2) • ~Equal numbers of affected males and females • Two affected individuals may have unaffected children • Generally, AA more severely affected, often die before birth or in childhood

34. Autosomal Dominant Pedigree

35. Autosomal Dominant Genetic Disorders

36. Animation: Chromosomes and Human Inheritance (autosomal-dominant inheritance)

37. Animation: Chromosomes and Human Inheritance (autosomal-recessive inheritance)

38. Neurofibromatosis (NF) • N = Neurofibromatosis 1; n = normal • Many different phenotypes • Café-au-lait spots, or noncancerous tumors in the nervous system can be large and press on nerves • Deformities of the face or other body parts (rarely) • NF gene has a very high mutation rate

39. Neurofibromatosis

40. Huntington Disease (HD) • H = Huntington disease; h = normal • Causes damage in brain from accumulation of huntingtin protein • Symptoms begin slowly (30–50 years old) • Affected individuals may have already had children (50% chance with one Hh parent) • Progressive neurological signs, no treatment, die within 10–25 years after symptoms

41. Adult-Onset Disorders • Expressed later in life • Present problems in pedigree analysis, genetic testing may be required • Examples: • Huntington disease (HD) • Adult polycystic kidney disease (ADPKD) • Both examples are autosomal dominant

42. 4.3 X-Linked Recessive Traits • Genes onX chromosome: X-linked • Genes on Y chromosome: Y-linked • For X-linked traits: • Females XX, XX*, or X*X* • Males XY or X*Y • Males cannot be homozygous or heterozygous, they are hemizygous for genes on X • Distinctive pattern of inheritance

43. X-Linked Recessive Inheritance • Mother gives one X chromosome to offspring • Father gives X to daughters and Y to sons • Sons carry X from mother • For recessive traits, X*X* and X*Y affected • More males affected

44. Pedigrees: X-Linked Inheritance

45. X-Linked Recessive Genetic Disorders

46. Inheritance of X-Linked Disorder

47. Animation: Chromosomes and Human Inheritance (X-linked inheritance)

48. Duchenne Muscular Dystrophy (DMD) (1) • XM = normal; Xm = muscular dystrophy • Most common form, affects ~1/3,500 males • Infants appear healthy, symptoms age ~1–6 years • Rapid, progressive muscle weakness • Usually must use a wheelchair by age 12 • Death, age ~20 from respiratory infection or cardiac failure

49. Duchenne Muscular Dystrophy (DMD) (2) • DMD gene on the end of X chromosome • Encodes protein dystrophin that supports plasma membrane during contraction • If dystrophin absent or defective, cells are torn apart • Two forms: DMD, and less-serious Becker muscular dystrophy (BMD)

50. Cells of a Person with MD