1. Overview: Locating Genes Along Chromosomes
Mendel’s “hereditary factors” were genes
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

2. Figure 15.1
Figure 15.1 Where are Mendel’s hereditary factors located in the cell?

3. CONCEPT 15.1: MENDELIAN INHERITANCE HAS ITS PHYSICAL BASIS IN THE BEHAVIOR OF CHROMOSOMES

4. Mendel and Meiosis Figure 15.2 The chromosomal basis of Mendel’s laws.
P Generation
Yellow-round seeds (YYRR)
Green-wrinkled seeds (yyrr) Y r y  R Y R r y
Meiosis
Fertilization R Y y r
Gametes
All F1 plants produce yellow-round seeds (YyRr).
F1 Generation R R y y r r Y Y
Meiosis
LAW OF SEGREGATION The two alleles for each gene separate during gamete formation.
LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation. R r r R
Metaphase I Y y Y y 1 1 R r r R
Anaphase I Y y Y y R r r R
Figure 15.2 The chromosomal basis of Mendel’s laws. 2 2 Y y
Metaphase II Y y y Y Y y Y Y y y
Gametes R R r r r r R R
1/4 YR
1/4 yr
1/4 Yr
1/4 yR
F2 Generation
An F1  F1 cross-fertilization 3
Fertilization recombines the R and r alleles at random. 3
Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 9
: 3
: 3
: 1

5. Mendel and Meiosis P Generation Yellow-round seeds (YYRR)
Green-wrinkled seeds (yyrr) Y y  r R Y R r y
Meiosis
Fertilization R Y y r
Gametes
Figure 15.2 The chromosomal basis of Mendel’s laws.

6. F1 Generation All F1 plants produce yellow-round seeds (YyRr).
Figure 15.2b
All F1 plants produce yellow-round seeds (YyRr).
F1 Generation R R y y r r Y Y
LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation.
LAW OF SEGREGATION The two alleles for each gene separate during gamete formation.
Meiosis R r r R
Metaphase I Y y Y y 1 1 R r r R
Anaphase I Y y Y y
Figure 15.2 The chromosomal basis of Mendel’s laws. R r r R
Metaphase II 2 2 Y y Y y Y y Y Y y Y y y
Gametes R R r r r r R R
1/4 YR
1/4 yr
1/4 Yr
1/4 yR

7. Mendel and Meiosis LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT
F2 Generation
An F1  F1 cross-fertilization 3
Fertilization recombines the R and r alleles at random. 3
Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 9
: 3
: 3
: 1
Figure 15.2 The chromosomal basis of Mendel’s laws.

8. Morgan’s Experimental Evidence for Mendel
The first solid evidence associating a specific gene with a specific chromosome came from Thomas Hunt Morgan, an embryologist
Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors

9. Morgan’s Choice of Experimental Organism
Several characteristics make fruit flies a convenient organism for genetic studies
They produce many offspring
A generation can be bred every two weeks
They have only four pairs of chromosomes

10. Morgan noted wild type, or normal, phenotypes that were common in the fly populations
Traits alternative to the wild type are called mutant phenotypes

11. Figure 15.4
EXPERIMENT
P Generation
The F1 generation all had red eyes
The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes
F1 Generation
All offspring had red eyes.
RESULTS
F2 Generation
CONCLUSION
P Generation w w X X X Y w w
Sperm
Eggs
F1 Generation w w
Figure 15.4 Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have? w
Morgan determined that the white-eyed mutant allele must be located on the X chromosome w w
Sperm
Eggs w w
F2 Generation w w w w w w

12. P Generation F1 Generation F2 Generation
EXPERIMENT
P Generation
F1 Generation
All offspring had red eyes.
RESULTS
Figure 15.4 Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have?
F2 Generation

13. P Generation F1 Generation F2 Generation
CONCLUSION
P Generation w w X X X Y w w
Sperm
Eggs
F1 Generation w w w w w
Sperm
Figure 15.4 Inquiry: In a cross between a wild-type female fruit fly and a mutant white-eyed male, what color eyes will the F1 and F2 offspring have?
Eggs w w
F2 Generation w w w w w w

14. CONCEPT 15.2: SEX-LINKED GENES EXHIBIT UNIQUE PATTERNS OF INHERITANCE
In humans and some other animals, there is a chromosomal basis of sex determination
CONCEPT 15.2: SEX-LINKED GENES EXHIBIT UNIQUE PATTERNS OF INHERITANCE

15. The Chromosomal Basis of Sex
Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome
The SRY gene on the Y codes for a protein that directs the development of male anatomical features X Y

16. Sex Determination Systems
44  XY
Parents
44  XX
Sex Determination Systems
22  X
22  Y
22  X or
Sperm
Egg
44  XX or
44  XY
Human males are XY
Human females are XX
Other organisms use different systems!
Zygotes (offspring)
(a) The X-Y system
22  XX
22  X
(b) The X-0 system
76  ZW
76  ZZ
(c) The Z-W system
32 (Diploid)
16 (Haploid)
(d) The haplo-diploid system

17. 44  XY 44  XX Parents 22  X 22  X 22  Y or Sperm Egg 44  XX
Figure 15.6a
44  XY
44  XX
Parents
22  X
22  X
22  Y or
Sperm
Egg
44  XX
44  XY or
Zygotes (offspring)
(a) The X-Y system
Figure 15.6 Some chromosomal systems of sex determination.
22  XX
22  X
(b) The X-0 system

18. 76  ZW 76  ZZ 32 (Diploid) 16 (Haploid)
Figure 15.6b
76  ZW
76  ZZ
(c) The Z-W system
32 (Diploid)
16 (Haploid)
Figure 15.6 Some chromosomal systems of sex determination.
(d) The haplo-diploid system

19. Sex-Linkage
A gene that is located on either sex chromosome is called a sex-linked gene
Genes on the Y = Y-linked genes; there are few of these
Genes on the X = X-linked genes

20. X-linked Inheritance
X chromosomes code for many genes not related to sex
Some disorders caused by recessive alleles on the X chromosome in humans
Color blindness (mostly X-linked)
Duchenne muscular dystrophy
Hemophilia

21. Transmitting X-linked genes: Colorblindness
XNXN
XnY
XNXn
XNY
XNXn
XnY
Sperm Xn Y
Sperm XN Y
Sperm Xn Y
Eggs XN
XNXn
XNY
Eggs XN
XNXN
XNY
Eggs XN
XNXn
XNY XN
XNXn
XNY Xn
XNXn
XnY Xn
XnXn
XnY
(a)
(b)
(c)
Figure 15.7 The transmission of X-linked recessive traits.
For a recessive X-linked trait to be expressed
A female needs two copies of the allele (homozygous)
A male needs only one copy of the allele (hemizygous)
X-linked recessive disorders are much more common in males than in females

22. X Inactivation in Female Mammals
In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development
The inactive X condenses into a Barr body
If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

23. Female Mosaics: X Inactivation
X chromosomes
Allele for orange fur
Early embryo:
Allele for black fur
Cell division and X chromosome inactivation
Two cell populations in adult cat:
Active X
Inactive X
Active X
Black fur
Orange fur
Figure 15.8 X inactivation and the tortoiseshell cat.

24. Each chromosome has hundreds or thousands of genes (except the Y chromosome)
Genes located on the same chromosome that tend to be inherited together are called linked genes
Concept 15.3: Linked genes tend to be inherited together Because of Location

25. Gene Linkage
Linked genes assort together

26. How Linkage Affects Inheritance
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
Double mutant (black body, vestigial wings)
Wild type (gray body, normal wings)

27. P Generation (homozygous) Double mutant (black body, vestigial wings)
Figure
EXPERIMENT
P Generation (homozygous)
Double mutant (black body, vestigial wings)
Wild type (gray body, normal wings)
b b vg vg
b b vg vg
Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?

28. P Generation (homozygous) Double mutant (black body, vestigial wings)
Figure
EXPERIMENT
P Generation (homozygous)
Double mutant (black body, vestigial wings)
Wild type (gray body, normal wings)
b b vg vg
b b vg vg
F1 dihybrid (wild type)
Double mutant
TESTCROSS
b b vg vg
b b vg vg
Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?

29. Wild type (gray-normal)
Figure
EXPERIMENT
P Generation (homozygous)
Double mutant (black body, vestigial wings)
Wild type (gray body, normal wings)
b b vg vg
b b vg vg
F1 dihybrid (wild type)
Double mutant
TESTCROSS
b b vg vg
b b vg vg
Testcross offspring
Eggs
b vg
b vg
b vg
b vg
Wild type (gray-normal)
Black- vestigial
Gray- vestigial
Black- normal
b vg
Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?
Sperm
b b vg vg
b b vg vg
b b vg vg
b b vg vg

30. Wild type (gray-normal)
Figure
EXPERIMENT
P Generation (homozygous)
Double mutant (black body, vestigial wings)
Wild type (gray body, normal wings)
b b vg vg
b b vg vg
F1 dihybrid (wild type)
Double mutant
TESTCROSS
b b vg vg
b b vg vg
Testcross offspring
Eggs
b vg
b vg
b vg
b vg
Wild type (gray-normal)
Black- vestigial
Gray- vestigial
Black- normal
b vg
Figure 15.9 Inquiry: How does linkage between two genes affect inheritance of characters?
Sperm
b b vg vg
b b vg vg
b b vg vg
b b vg vg
PREDICTED RATIOS
If genes are located on different chromosomes: 1 : 1 : 1 : 1
If genes are located on the same chromosome and parental alleles are always inherited together: 1 : 1 : :
RESULTS
965 :
944 :
206 :
185

31. b+ vg+
b vg
F1 dihybrid female and homozygous recessive male in testcross
b vg
b vg
b+ vg+
b vg
Most offspring or
b vg
b vg
Figure 15.UN01 In-text figure, p. 294
Morgan found body color and wing size are usually inherited together in specific combinations (parental phenotypes)

32. However, nonparental phenotypes were also produced
Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent

33. Genetic Recombination and Linkage
Offspring with a phenotype matching one of the parental phenotypes are called parental types
Offspring with nonparental phenotypes are called recombinant types, or recombinants
A 50% frequency of recombination is observed for any two genes on different chromosomes

34. Parental vs. Recombinant Phenotypes
Gametes from yellow-round dihybrid parent (YyRr) YR yr Yr yR
Gametes from green- wrinkled homozygous recessive parent (yyrr) yr
YyRr
yyrr
Yyrr
yyRr
Figure 15.UN02 In-text figure, p. 294
Parental- type offspring
Recombinant offspring

35. Recombination of Linked Genes: Crossing Over
Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed
Some process must occasionally break the physical connection between genes on the same chromosome

36. Crossing Over and Recombination
Testcross parents
Gray body, normal wings (F1 dihybrid)
Black body, vestigial wings (double mutant)
Crossing Over and Recombination
b vg
b vg
b vg
b vg
Replication of chromosomes
Replication of chromosomes
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Meiosis I
b vg
Meiosis I and II
Recombinant chromosomes bring alleles together in new combinations in gametes
Genetic variation drives evolution!
b vg
b vg
b vg
Meiosis II
Recombinant chromosomes
bvg
b vg
b vg
b vg
Eggs
Figure Chromosomal basis for recombination of linked genes.
Testcross offspring
965 Wild type (gray-normal)
944 Black- vestigial
206 Gray- vestigial
185 Black- normal
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
b vg
Sperm
Parental-type offspring
Recombinant offspring
Recombination frequency
391 recombinants 2,300 total offspring 
  17%

37. Recombination frequencies
Mapping Distance Between Genes Using Recombination Data
Recombination frequencies
1 map unit = 1% recombination frequency 9%
9.5%
Chromosome
17% b cn vg
A linkage map is a genetic map of a chromosome based on recombination frequencies
The farther apart two genes are, the higher the probability crossover will occur and therefore the higher the recombination frequency
Distances between genes can be expressed as map units.
Figure Research Method: Constructing a Linkage Map

38. Genes that are far apart on the same chromosome can have a recombination frequency near 50%
Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes

39. Genetic Linkage Map: Cytogenic Mapping
Mutant phenotypes
Short aristae
Black body
Cinnabar eyes
Vestigial wings
Brown eyes
48.5
57.5
67.0
104.5
Figure A partial genetic (linkage) map of a Drosophila chromosome.
Long aristae (appendages on head)
Gray body
Red eyes
Normal wings
Red eyes
Wild-type phenotypes

40. Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders
Plants tolerate such genetic changes better than animals do
Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders

41. Chromosomal Changes and Disorders
Abnormal Chromosome Number
Alteration of Chromosome Structure

42. Abnormal Chromosome Number
Meiosis I
Nondisjunction
In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis
Figure Meiotic nondisjunction.

43. Abnormal Chromosome Number
Meiosis I
Nondisjunction
Meiosis II
Non- disjunction
As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy
Figure Meiotic nondisjunction.

44. Abnormal Chromosome Number
Meiosis I
Nondisjunction
Meiosis II
Non- disjunction
Gametes
Figure Meiotic nondisjunction.
n  1
n  1
n  1
n  1
n  1
n  1 n n
Number of chromosomes
Nondisjunction of homo- logous chromosomes in meiosis I
(a)
Nondisjunction of sister chromatids in meiosis II
(b)

45. Aneuploidy
The fertilization of gametes in which nondisjunction occurred
Offspring with this condition have an abnormal number of a particular chromosome

46. A monosomic zygote has only one copy of a particular chromosome
A trisomic zygote has three copies of a particular chromosome

47. Polyploidy: More than 2 Sets of Chromosomes
Triploidy (3n) is three sets of chromosomes
Tetraploidy (4n) is four sets of chromosomes
Polyploidy is common in plants, but not animals
Polyploids are more normal in appearance than aneuploids
Hexaploidy (6n)
Triploidy (3n)
Octoploidy (8n)

48. 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 orientation of a segment within a chromosome
Translocation moves a segment from one chromosome to another

49. Alterations of Chromosome Structure
(a) Deletion A C D E F G H B
A deletion removes a chromosomal segment. A B C E F G H
(b) Duplication A B C D E F G H
Figure Alterations of chromosome structure.
A duplication repeats a segment. A B C D E F G H

50. Alterations of Chromosome Structure
(c) Inversion A B C D E F G H
An inversion reverses a segment within a chromosome. A D C B E F G H
(d) Translocation A B C D E F G H M N O P Q R
Figure Alterations of chromosome structure.
A translocation moves a segment from one chromosome to a nonhomologous chromosome. G M N O C H F E D A B P Q R

51. Human Disorders Due to Chromosomal Alterations
Most mammalian aneuploidy are lethal but some survive to birth and beyond
These surviving individuals have a set of symptoms, or syndrome.

52. Down Syndrome (Trisomy 21)
Down syndrome is an aneuploid condition that results from three copies of chromosome 21
It affects about 1in 700 children born in the US
The frequency of Down syndrome increases with the age of the mother

53. Aneuploidy of Sex Chromosomes
Syndrome
Genotype
Occurrence
Symptoms
Klinefelter Syndrome
XXY
1/500 ~ 1/1000
Underdeveloped testes
Male is sterile
Some secondary female characteristics
XYY Syndrome
XYY
1/1000
Normal sexual development
Taller than average
Increased aggression
Turner Syndrome (Monosomy X) XO
1/2500
Only viable monosomy in humans
Sex organs do not develop; sterile
Trisomy X
XXX
Learning disabled
Fertile
Slightly taller

54. Turner’s Syndrome
Klinefelter Syndrome

55. Disorders Caused by Structurally Altered Chromosomes
The 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

56. CML: Chronic Myelogenous Leukemia
Normal chromosome 9
CML caused by translocations of chromosomes
Normal chromosome 22
Reciprocal
translocation
Figure Translocation associated with chronic myelogenous leukemia (CML).
Translocated chromosome 9
Translocated chromosome 22 (Philadelphia chromosome)

57. Concept 15.5: Some inheritance patterns are exceptions to standard Mendelian inheritance
There are two normal exceptions to Mendelian genetics
One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleus
In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance

58. 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

59. Normal Igf2 allele is expressed.
Figure 15.17
Normal Igf2 allele is expressed.
Paternal chromosome
Maternal chromosome
Normal-sized mouse (wild type)
Normal Igf2 allele is not expressed.
(a) Homozygote
Mutant Igf2 allele inherited from mother
Mutant Igf2 allele inherited from father
Normal-sized mouse (wild type)
Dwarf mouse (mutant)
Figure Genomic imprinting of the mouse Igf2 gene.
Normal Igf2 allele is expressed.
Mutant Igf2 allele is expressed.
Mutant Igf2 allele is not expressed.
Normal Igf2 allele is not expressed.
(b) Heterozygotes

60. It appears that imprinting is the result of the methylation (addition of —CH3) of cysteine nucleotides
Genomic imprinting is thought to affect only a small fraction of mammalian genes
Most imprinted genes are critical for embryonic development

61. Inheritance of Organelle Genes
Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasm
Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules
Extranuclear genes are inherited maternally 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

62. Figure 15.18
Figure Variegated leaves from English holly (Ilex aquifolium).

63. Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems
For example, mitochondrial myopathy and Leber’s hereditary optic neuropathy

64. Sperm Egg C c B b D A d E a P generation gametes e F f
Figure 15.UN03
Sperm
Egg C c B b D A d E a
P generation gametes e F f
The alleles of unlinked genes are either on separate chromosomes (such as d and e) or so far apart on the same chromosome (c and f) that they assort independently.
This F1 cell has 2n  6 chromo- somes and is heterozygous for all six genes shown (AaBbCcDdEeFf). Red  maternal; blue  paternal. D e C B d
Figure 15.UN03 In-text figure, p. 294 A
Genes on the same chromo- some whose alleles are so close together that they do not assort independently (such as a, b, and c) are said to be genetically linked.
Each chromosome has hundreds or thousands of genes. Four (A, B, C, F) are shown on this one. E F f a c b

65. Figure 15.UN04
Figure 15.UN04 In-text figure, p. 294

66. Figure 15.UN05
Figure 15.UN05 In-text figure, p. 294

67. Figure 15.UN06
Figure 15.UN06 In-text figure, p. 294