1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Chapter 15 The Chromosomal Basis of Inheritance

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview: Locating Genes on Chromosomes A century ago the relationship between genes and chromosomes was not obvious Today we can show that genes are located on chromosomes The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mendelian inheritance has its physical basis in the behavior of chromosomes Several researchers proposed in the early 1900s that genes are located on chromosomes The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

5. The chromosome theory of inheritance ( formulated by Walter Sutton in1902) states that: – Mendelian genes have specific loci (positions) on chromosomes – It is the chromosomes that undergo segregation and independent assortment (during metaphase I and anaphase I of Meiosis)

6. LE 15-2 P Generation Gametes Meiosis Yellow-round seeds (YYRR) Fertilization Green-wrinkled seeds (yyrr) All F 1 plants produce yellow-round seeds (YyRr) Meiosis Two equally probable arrangements of chromosomes at metaphase I Anaphase I LAW OF INDEPENDENT ASSORTMENT Metaphase II Fertilization among the F 1 plants F 2 Generation Gametes F 1 Generation LAW OF SEGREGATION

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Morgan’s Experimental Evidence: Scientific Inquiry The first solid evidence associating a specific gene with a a specific chromosome came from Thomas Hunt Morgan, an embryologist Morgan’s experiments with fruit flies (Columbia University, 1910) provided convincing evidence that chromosomes are the location of Mendel’s heritable factors. He provided confirmation of the correctness of the chromosomal theory of inheritance.

8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Morgan’s Choice of Experimental Organism Characteristics that make fruit flies a convenient organism for genetic studies: – They breed at a high rate – A generation can be bred every two weeks – They have only four pairs of chromosomes

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Morgan noted wild type, or normal, phenotypes that were common in the fly populations Traits alternative to the wild type are called mutant phenotypes Studying the fruit fly ( Drosophila melanogaster) detected a mutant male fly, one with white eyes instead of red.

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

11. Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) – The F 1 generation all had red eyes – Morgan then crossed the red eyes flies from the F1 generation with each other – The F 2 generation showed the 3:1 red:white eye ratio, but only males had white eyes

12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Morgan’s experiment continued… How can you explain only males had white eyes? Morgan determined that the white-eye mutant allele must be located on the X chromosome ( it is absent in the Y chromosome) A trait determined by a gene on the sex chromosomes is said to be “sex linked ” Morgan’s finding supported the chromosome theory of inheritance. In other words: Mendelian traits assort independently because they are determined by genes located on chromosomes that assort independently in meiosis.

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Linked genes tend to be inherited together because they are located near each other on the same chromosome Each chromosome has hundreds or thousands of genes Genes located on the same chromosome that tend to be inherited together are called linked genes

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How Linkage Affects Inheritance: Scientific Inquiry Morgan did other experiments with fruit flies to see how linkage affects inheritance of two characters Morgan crossed flies that differed in traits of body color and wing size

15. LE 15-5 P Generation (homozygous) Parental-type offspring Double mutant (black body, vestigial wings) Recombinant (nonparental-type) offspring b b vg vg Double mutant (black body, vestigial wings) b b vg vg Ova Sperm TESTCROSS 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Wild type (gray body, normal wings) b + b + vg + vg + F 1 dihybrid (wild type (gray body, normal wings) b + b vg + vg

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings From the results, Morgan reasoned that body color and wing size are usually inherited together in specific combinations (parental phenotypes) because the genes are on the same chromosome However, nonparental phenotypes were also produced Understanding this result involves exploring genetic recombination, production of offspring with combinations of traits differing from either parent

17. LE 15-UN278-1 Parents in testcross Most offspring or

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genetic Recombination and Linkage The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Each chromosome has hundreds or thousands of genes. Genes located on the same chromosome, linked genes, tend to be inherited together because the chromosome is passed along as a unit. Results of crosses with linked genes deviate from those expected according to independent assortment. Linked genes tend to be inherited together because they are located on the same chromosome Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked, but the linkage was incomplete, as evident from recombinant phenotypes Morgan proposed that some process must sometimes break the physical connection between genes on the same chromosome That mechanism was the crossing over of homologous chromosomes

21. LE 15-6 Testcross parents Parental-type offspring Recombinant offspring Ova Sperm 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Gray body, normal wings (F 1 dihybrid) Sperm Testcross offspring Recombination frequency 391 recombinants 2,300 total offspring  100 = 17% = Ova Gametes Replication of chromosomes Black body, vestigial wings (double mutant) Replication of chromosomes Meiosis I and II: No new allele combinations are produced. Meiosis I: Crossing over between b and vg loci produces new allele combinations. Recombinant chromosomes Meiosis II: Separation of chromatids produces recombinant gametes with the new allele combinations.

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 15.3: Sex-linked genes exhibit unique patterns of inheritance In humans and other animals, there is a chromosomal basis of sex determination

23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Chromosomal Basis of Sex An organism’s sex is an inherited phenotypic character determined by the presence or absence of certain chromosomes In humans and other mammals, there are two varieties of sex chromosomes, X and Y Other animals have different methods of sex determination

24. LE 15-9 The X-Y system The X-0 system The Z-W system The haplo-diploid system Parents Sperm Ova Zygotes (offspring)

25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inheritance of Sex-Linked Genes The sex chromosomes have genes for many characters unrelated to sex A gene located on either sex chromosome is called a sex-linked gene Sex-linked genes follow specific patterns of inheritance

26. LE 15-10 Sperm Ova Sperm Ova Sperm Ova

27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

28. SEX LINKED INHERITANCE CHROMOSOMES Humans have 22 pairs of AUTOSOMES and one pair of SEX CHROMOSOMES : total=23 prs Thomas Morgan discovered SEX LINKED INHERITANCE studying Drosophila (fruit fly) In fruit flies red eyes is the wild type and white eyes is a mutant. He noticed the connection between gender and certain traits. Only the male flies had mutant white eyes.

29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings SEX LINKED TRAITS ARE THOSE CARRIED BY THE X CHROMOSOME Red-Green color blindness Inability to see those colors. Red and green look all the same,like gray Hemophilia Blood clotting disorder. The clotting factor VIII is not made, individual can bleed to death. Muscular dystrophy X linked recessive, gradual and progressive destruction of skeletal muscles. Faulty teeth enamel Extremely rare, X linked Dominant

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Some disorders caused by recessive alleles on the X chromosome in humans: – Color blindness – Duchenne muscular dystrophy – Hemophilia

31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Some serious human disorders are sex-linked Duchenne muscular dystrophy – affects one in 3,500 males born in the United States. – Affected individuals rarely live past their early 20s. – This disorder is due to the absence of an X- linked gene for a key muscle protein, called dystrophin. – The disease is characterized by a progressive weakening of the muscles and loss of coordination.

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders

33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Abnormal Chromosome Number In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy

34. LE 15-12 Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n + 1 Number of chromosomes Nondisjunction of homologous chromosomes in meiosis I n + 1n – 1 n + 1n – 1nn Nondisjunction of sister chromatids in meiosis I

35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Aneuploidy results from the fertilization of gametes in which nondisjunction occurred Offspring with this condition have an abnormal number of a particular chromosome

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings A trisomic zygote has three copies of a particular chromosome A monosomic zygote has only one copy of a particular chromosome Polyploidy is a condition in which an organism has more than two complete sets of chromosomes. This happens more often in plants.

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

38. INHERITED DISORDERS DUE TO CHROMOSOMES CHANGES Chromosome changes can cause a lot of genetic disorders as well as a lot of variety WHEN AND HOW CAN A CHROMOSOME CHANGE? Mistakes in replication. During the S phase of the cell cycle segments of a chromosome could be deleted, duplicated, inverted or translocation (moved to a new location). Also during Metaphase I (meiosis) there can be improper separation after duplication. This can change the total number of chromosomes in each gamete of the new individual.

39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings If during meiosis the paired chromatids fail to separate correctly this is called NON-DISJUNCTION ANEUPLOIDY means an abnormal number of chromosomes. When an individual ends up with the wrong number of chromosomes most of the time it is miscarried ( spontaneous abortion). The wrong number of somatic chromosomes are almost always lethal. Ex: trisomy 21(three chrom. 21): Down Syndrome You can live with the wrong number of sex pair chromosomes.

40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure: – Deletion removes a chromosomal segment – Duplication repeats a segment – Inversion reverses a segment within a chromosome – Translocation moves a segment from one chromosome to another

41. LE 15-14 Deletion Duplication Inversion Reciprocal translocation A deletion removes a chromosomal segment. A duplication repeats a segment. An inversion reverses a segment within a chromosome. A translocation moves a segment from one chromosome to another, nonhomologous one.

42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Human Disorders Due to Chromosomal Alterations Alterations of chromosome number and structure are associated with some serious disorders Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Down Syndrome Down syndrome is an aneuploid condition that results from three copies of chromosome 21 It affects about one out of every 700 children born in the United States The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained

44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

45. Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes produces a variety of aneuploid conditions Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans

46. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Disorders Caused by Structurally Altered Chromosomes One syndrome, cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5 A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes

47. LE 15-16 Reciprocal translocation Normal chromosome 9 Normal chromosome 22 Translocated chromosome 9 Translocated chromosome 22 Philadelphia chromosome

48. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Errors and Exceptions in Chromosomal Inheritance 1.Alterations of chromosome number or structure cause some genetic disorders 2.The phenotypic effects of some mammalian genes depend on whether they are inherited from the mother or the father (imprinting) 3. Extranuclear genes exhibit a non-Mendelian pattern of inheritance

49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genomic Imprinting For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits Such variation in phenotype is called genomic imprinting Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production

50. LE 15-17 Normal lgf2 allele (expressed) Normal lgf2 allele (not expressed) Wild-type mouse (normal size) Paternal chromosome Maternal chromosome A wild-type mouse is homozygous for the normal lgf2 allele. Normal lgf2 allele (expressed) Mutant lgf2 allele (not expressed) Normal size mouse Paternal Maternal Mutant lgf2 allele (expressed) Normal lgf2 allele (not expressed) Dwarf mouse Paternal Maternal When a normal lgf2 allele is inherited from the father, heterozygous mice grow to normal size. But when a mutant allele is inherited from the father, heterozygous mice have the dwarf phenotype.

51. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 15.5: Some inheritance patterns are exceptions to the standard chromosome theory One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleus

52. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inheritance of Organelle Genes Extranuclear genes are genes found in organelles in the cytoplasm such as those found in the mitochondria The inheritance of traits controlled by extranuclear genes comes from the maternal parent because the zygote’s cytoplasm comes from the egg The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant

53. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

54. Some diseases affecting the muscular and nervous systems are caused by defects in mitochondrial genes that prevent cells from making enough ATP