Genetics

1. Genetics The study of inherited traits: An introduction

2. Molecular Genetics Cell Chromosome DNA Nucleus Nucleotides

3. History of Genetics • Mid 19th century (1850) • Darwin & Wallace • Theories of evolution • Lamarck • Theories on acquisition of heritable traits • Mendel • Theories on transmission of traits

4. History of Genetics • Pioneering work of Mendel was done in ignorance of cell division – particularly meiosis, and the nature of genetic material – DNA • 1869 - Friedrich Miescher identified DNA • 1900-1913 • Chromosomal theory of inheritance – Sutton & Boveri • Genes on chromosomes – TH Morgan • Genes linearly arranged on chromosomes & mapped – AH Sturtevant • 1941 – George Beadle & Ed Tatum related "gene" to enzyme & biochemical processes • 1944 – Oswald Avery demonstrated that DNA was genetic material

5. Early Ideas • Until the 20th century, many biologists erroneously believed that • characteristics acquired during lifetime could be passed on • characteristics of both parents blended irreversibly in their offspring

6. Mendel • Modern genetics began with Gregor Mendel’s quantitative experiments with pea plants Stamen Carpel Figure 9.2A, B

7. White 1 Removed stamensfrom purple flower • Mendel crossed pea plants that differed in certain characteristics and traced the traits from generation to generation Stamens Carpel 2 Transferred pollen from stamens of white flower to carpel of purple flower PARENTS(P) Purple 3 Pollinated carpel matured into pod • This illustration shows his technique for cross-fertilization 4 Planted seeds from pod OFF-SPRING(F1) Figure 9.2C

8. FLOWER COLOR Purple White • Mendel studied seven pea characteristics - phenotypes FLOWER POSITION Axial Terminal • He hypothesized that there are alternative forms of genes (although he did not use that term), the units that determine heredity SEED COLOR Yellow Green SEED SHAPE Round Wrinkled POD SHAPE Inflated Constricted POD COLOR Green Yellow STEM LENGTH Figure 9.2D Tall Dwarf

9. Principle of Segregation P GENERATION(true-breedingparents) • From his experimental data, Mendel deduced that an organism has two genes (alleles) for each inherited characteristic • One characteristic (phenotype) comes from each parent Purple flowers White flowers All plants have purple flowers F1generation Fertilization among F1 plants(F1 x F1) F2generation 3/4 of plantshave purple flowers 1/4 of plantshave white flowers Figure 9.3A

10. GENETIC MAKEUP (ALLELES) PLANTS PP pp Gametes All P All p • A sperm or egg carries only one allele of each pair • The pairs of alleles separate when gametes form • This process describes Mendel’s law of segregation • Alleles can be dominant or recessive F1 PLANTS(hybrids) All Pp Gametes 1/2P 1/2p P P Eggs Sperm PP F2 PLANTS p p Pp Pp Phenotypic ratio3 purple : 1 white pp Genotypic ratio1 PP : 2 Pp : 1 pp Figure 9.3B

11. Homologous chromosomes bear the two alleles for each characteristic • Alternative forms of a gene (alleles) reside at the same locus on homologous chromosomes GENE LOCI DOMINANT allele P a B P a b RECESSIVE allele GENOTYPE: PP aa Bb HOMOZYGOUSfor thedominant allele HOMOZYGOUSfor therecessive allele HETEROZYGOUS Figure 9.4

12. The principle of independent assortment • By looking at two characteristics at once, Mendel found that the alleles of a pair segregate independently of other allele pairs during gamete formation • This is known as the principle of independent assortment

13. HYPOTHESIS: DEPENDENT ASSORTMENT HYPOTHESIS: INDEPENDENT ASSORTMENT RRYY rryy PGENERATION RRYY rryy ry ry Gametes RY Gametes RY F1GENERATION RrYy RrYy Eggs 1/2 RY 1/2 RY Sperm Eggs 1/4 RY 1/4 RY 1/2 ry 1/2 ry 1/4 rY 1/4 rY RRYY 1/4 Ry 1/4 Ry RrYY RrYY F2GENERATION 1/4 ry 1/4 ry RRYy rrYY RrYy Yellow round RrYy RrYy RrYy RrYy 9/16 Actual resultscontradict hypothesis Green round rrYy RRyy rrYy 3/16 ACTUAL RESULTSSUPPORT HYPOTHESIS Yellow wrinkled Rryy Rryy 3/16 Yellow wrinkled rryy 1/16 Figure 9.5A

14. Independent assortment of two genes in the Labrador retriever Blind Blind Black coat, normal visionB_N_ Black coat, blind (PRA)B_nn Chocolate coat, normal visionbbN_ Chocolate coat, blind (PRA)bbnn PHENOTYPES GENOTYPES MATING OF HETEROZYOTES(black, normal vision) BbNn BbNn 9 black coat,normal vision 3 black coat,blind (PRA) 3 chocolate coat,normal vision 1 chocolate coat,blind (PRA) PHENOTYPIC RATIO OF OFFSPRING Figure 9.5B

15. Geneticists use testcross to determine unknown genotypes • The offspring of a testcross often reveal the genotype of an individual when it is unknown TESTCROSS: GENOTYPES B_ bb Two possibilities for the black dog: BB or Bb B B b GAMETES b Bb b Bb bb OFFSPRINGa Figure 9.6 All black 1 black : 1 chocolate

16. Mendel’s principles reflect the rules of probability • Inheritance follows the rules of probability • The rule of multiplication and the rule of addition can be used to determine the probability of certain events occurring F1 GENOTYPES Bb female Bb male Formation of eggs Formation of sperm 1/2 B B 1/2 B B 1/2 b b 1/2 1/4 B b b B 1/4 1/4 b b F2 GENOTYPES 1/4 Figure 9.7

17. Family pedigrees • The inheritance of many human traits follows Mendel’s principles and the rules of probability Figure 9.8A

18. Family pedigrees are used to determine patterns of inheritance and individual genotypes Dd Joshua Lambert Dd Abigail Linnell D_ JohnEddy ? D_ HepzibahDaggett ? D_ Abigail Lambert ? dd JonathanLambert Dd Elizabeth Eddy Dd Dd dd Dd Dd Dd dd Female Male Deaf Hearing Figure 9.8B

19. Many inherited disorders are controlled by a single gene • Most such disorders are caused by autosomalrecessive alleles • Examples: cystic fibrosis, sickle-cell disease Normal Dd Normal Dd PARENTS D D Eggs Sperm DD Normal d d Dd Normal (carrier) Dd Normal (carrier) OFFSPRING dd Deaf Figure 9.9A

20. Examples: achondroplasia, Huntington’s disease • A few are caused by dominant alleles Figure 9.9B

21. Table 9.9

22. Fetal testing for inherited disorders • Karyotyping and biochemical tests of fetal cells and molecules can help people make reproductive decisions • Fetal cells can be obtained through amniocentesis Amnioticfluidwithdrawn Centrifugation Amnioticfluid Fluid Fetalcells Fetus(14-20weeks) Biochemicaltests Placenta Severalweeks later Figure 9.10A Uterus Cervix Karyotyping Cell culture

23. Chorionic villus sampling is another procedure that obtains fetal cells for karyotyping Fetus(10-12weeks) Several hourslater Placenta Suction Karyotyping Fetal cells(from chorionic villi) Some biochemical tests Chorionic villi Figure 9.10B

24. Examination of the fetus with ultrasound is another helpful technique Figure 9.10C, D

25. VARIATIONS ON MENDEL’S PRINCIPLES The relationship of genotype to phenotype is rarely simple • Mendel’s principles are valid for all sexually reproducing species • However, often the genotype does not dictate the phenotype in the simple way his principles describe

26. Incomplete dominance results in intermediate phenotypes P GENERATION Whiterr • When an offspring’s phenotype—such as flower color— is in between the phenotypes of its parents, it exhibits incomplete dominance Red RR Gametes R r PinkRr F1 GENERATION 1/2 R 1/2 r 1/2 R 1/2 R Eggs Sperm RedRR 1/2 r 1/2 r PinkRr PinkrR F2 GENERATION Whiterr Figure 9.12A

27. Incomplete dominance in human hypercholesterolemia GENOTYPES: HH Homozygousfor ability to makeLDL receptors Hh Heterozygous hh Homozygousfor inability to makeLDL receptors PHENOTYPES: LDL LDLreceptor Cell Normal Mild disease Severe disease Figure 9.12B

28. 9.13 Many genes have more than two alleles in the population • In a population, multiple alleles often exist for a characteristic • The three alleles for ABO blood type in humans is an example

29. The alleles for A and B blood types are codominant, and both are expressed in the phenotype BloodGroup(Phenotype) AntibodiesPresent in Blood Reaction When Blood from Groups Below Is Mixed with Antibodies from Groups at Left Genotypes O A B AB Anti-A Anti-B O ii IA IA or IA i A Anti-B IB IB or IB i B Anti-A AB IA IB Figure 9.13

30. 9.14 A single gene may affect many phenotypic characteristics • A single gene may affect phenotype in many ways • This is called pleiotropy • The allele for sickle-cell disease is an example

31. Individual homozygousfor sickle-cell allele Sickle-cell (abnormal) hemoglobin Abnormal hemoglobin crystallizes,causing red blood cells to become sickle-shaped Sickle cells Clumping of cells and clogging of small blood vessels Accumulation ofsickled cells in spleen Breakdown of red blood cells Physical weakness Heart failure Pain and fever Brain damage Damage to other organs Spleen damage Anemia Pneumonia and other infections Impaired mental function Kidney failure Rheumatism Paralysis Figure 9.14

32. Genetic testing to detect disease-causing alleles • Genetic testing can be of value to those at risk of developing a genetic disorder or of passing it on to offspring Figure 9.15B • Dr. David Satcher, former U.S. surgeon general, pioneered screening for sickle-cell disease Figure 9.15A

33. A single characteristic may be influenced by many genes • This situation creates a continuum of phenotypes • Example: skin color • Polygenic inheritance

34. P GENERATION aabbcc(very light) AABBCC(very dark) F1 GENERATION AaBbCc AaBbCc Eggs Sperm Fraction of population Skin pigmentation F2 GENERATION Figure 9.16

35. THE CHROMOSOMAL BASIS OF INHERITANCE Chromosome behavior accounts for Mendel’s principles • Genes are located on chromosomes • Their behavior during meiosis accounts for inheritance patterns

36. The chromosomal basis of Mendel’s principles Figure 9.17

37. Genes on the same chromosome tend to be inherited together • Certain genes are linked • They tend to be inherited together because they reside close together on the same chromosome

38. Figure 9.18

39. Crossing over produces new combinations of alleles • This produces gametes with recombinant chromosomes • The fruit fly Drosophila melanogaster was used in the first experiments to demonstrate the effects of crossing over

40. A B a b B A a b A b a B Tetrad Crossing over Gametes Figure 9.19A, B

41. Figure 9.19C

42. 9.20 Geneticists use crossover data to map genes • Crossing over is more likely to occur between genes that are farther apart • Recombination frequencies can be used to map the relative positions of genes on chromosomes Chromosome g c l 17% 9% 9.5% Figure 9.20B

43. Alfred H. Sturtevant, seen here at a party with T. H. Morgan and his students, used recombination data from Morgan’s fruit fly crosses to map genes Figure 9.20A

44. Mutant phenotypes • A partial genetic map of a fruit fly chromosome Shortaristae Black body (g) Cinnabar eyes (c) Vestigial wings (l) Browneyes Long aristae(appendageson head) Gray body (G) Red eyes (C) Normal wings (L) Redeyes Wild-type phenotypes Figure 9.20C

45. SEX CHROMOSOMES AND SEX-LINKED GENES Chromosomes determine sex in many species • A human male has one X chromosome and one Y chromosome • A human female has two X chromosomes • Whether a sperm cell has an X or Y chromosome determines the sex of the offspring

46. (male) (female) Parents’diploidcells X Y Male Sperm Egg Offspring(diploid) Figure 9.21A

47. Other systems of sex determination exist in other animals and plants • The X-O system • The Z-W system • Chromosome number Figure 9.21B-D

48. Sex-linked genes exhibit a unique pattern of inheritance • All genes on the sex chromosomes are said to be sex-linked • In many organisms, the X chromosome carries many genes unrelated to sex • Fruit fly eye color is a sex-linked characteristic Figure 9.22A

49. These figures illustrate inheritance patterns for white eye color (r) in the fruit fly, an X-linked recessive trait • Their inheritance pattern reflects the fact that males have one X chromosome and females have two Female Male Female Male Female Male XRXR XrY XRXr XRY XRXr XrY XR Xr XR XR XR Xr Y XRXr XRXR XRXr Y Y Xr Xr XRY XrXR XRY XrXr XRY XrY XrY R = red-eye allele r = white-eye allele Figure 9.22B-D

50. Sex-linked disorders affect mostly males • Most sex-linked human disorders are due to recessive alleles • Examples: hemophilia, red-green color blindness • These are mostly seen in males • A male receives a single X-linked allele from his mother, and will have the disorder, while a female has to receive the allele from both parents to be affected Figure 9.23A