1. NOTES: Ch 15 - Chromosomes, Sex Determination & Sex Linkage

2. 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. The Chromosome Theory of Inheritance states that:
● Mendelian genes have specific loci (positions) on chromosomes
● It is the chromosomes that undergo segregation and independent assortment!

4. P Generation
Yellow-round
seeds (YYRR)
Green-wrinkled
seeds (yyrr)
Meiosis
Fertilization
Gametes
All F1 plants produce
yellow-round seeds (YyRr)
F1 Generation
Meiosis
LAW OF SEGREGATION
LAW OF INDEPENDENT ASSORTMENT
Two equally
probable
arrangements
of chromosomes
at metaphase I
Anaphase I
Metaphase II
Gametes
F2 Generation
Fertilization among the F1 plants

5. 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

6. Morgan’s Choice of Experimental Organism: Fruit Flies!
● 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

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

10. 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 F1 generation all had red eyes
-The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes
● Morgan determined that the white-eye mutant allele must be located on the X chromosome
● Morgan’s finding supported the chromosome theory of inheritance!

11. P
Generation F1
Generation F2
Generation P
Generation
Ova
(eggs)
Sperm F1
Generation
Ova
(eggs)
Sperm F2
Generation

12. Linkage
&
Gene Maps

13. The Big Question…
● It may be easy to see that genes located on DIFFERENT chromosomes assort independently but what about genes located on the SAME chromosome?

14. Thomas Morgan’s Research
● Morgan identified more than 50 genes on Drosophila’s 4 chromosomes.
● He discovered that many seemed to be “linked” together
They are almost always inherited together & only rarely become separated
● Grouped genes into 4 linkage groups

15. Hmmm...
4 chromosomes
& 4 linkage groups

16. Morgan’s Conclusion:
● Each chromosome is actually a group of linked genes
● BUT Mendel’s principle of independent assortment still holds true
● It is the chromosomes that assort independently!!
Mendel missed this because 6 of the 7 traits he studied were on different chromosomes.

17. So…
● If 2 genes are found on the same chromosome are they linked forever?
NO!!
● CROSSING OVER during Meiosis can separate linked genes

18. Parental-type offspring Recombinant offspring
Testcross
parents
Gray body,
normal wings
(F1 dihybrid)
Black body,
vestigial wings
(double mutant)
Replication of
chromosomes
Replication of
chromosomes
Meiosis I: Crossing
over between b and vg
loci produces new allele
combinations.
Meiosis I and II:
No new allele
combinations are
produced.
Meiosis II: Separation
of chromatids produces
recombinant gametes
with the new allele
combinations.
Recombinant
chromosomes
Ova
Sperm
Gametes
Ova
Testcross
offspring
965
Wild type
(gray-normal)
944
Black-
vestigial
206
Gray-
vestigial
185
Black-
normal
Sperm
Recombination
frequency =
391 recombinants
 100 = 17%
2,300 total offspring
Parental-type offspring
Recombinant offspring

19. Gene Maps
● Alfred Sturtevant was a graduate student working in Morgan’s lab part-time in 1911
● He hypothesized that the farther apart 2 genes are on a chromosome the more likely they are to be separated by crossing-over
● The rate of at which linked genes are separated can be used to produce a “map” of distances between genes
Alfred Sturtevant

21. Gene Maps
● This map shows the relative locations of each known gene on a chromosome

22. Linkage Maps
● A linkage map is a genetic map of a chromosome based on recombination frequencies
● Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency
● Map units indicate relative distance and order, not precise locations of genes

23. Recombination
frequencies 9%
9.5%
17% b cn vg
Chromosome

24. I IV II Y X
III
Mutant phenotypes
Short
aristae
Black
body
Cinnabar
eyes
Vestigial
wings
Brown
eyes
48.5
57.5
67.0
104.5
Long aristae
(appendages
on head)
Gray
body
Red
eyes
Normal
wings
Red
eyes
Wild-type phenotypes

25. Sex-linked genes exhibit unique patterns of inheritance
● In humans and other animals, there is a chromosomal basis of sex determination

26. XX XY ● Human somatic cells contain 23 pairs of chromosomes
-22 pairs of autosomes (same in males & females)
-1 pair of sex chromosomes (XX or XY)
-Females have 2 matching sex chromosomes: XX
-Males are XY XX XY

27. 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

28. Sperm
Sperm
Sperm
Ova
Ova
Ova

29. ● Some disorders caused by recessive alleles on the X chromosome in humans:
-Color blindness
-Duchenne muscular dystrophy
-Hemophilia

31. ● When a gene is located on the X chromosome, females receive 2 copies of the gene, and males receive only 1 copy
Example: Color-blindness (c) is recessive to normal vision (C), and it is located on the X chromosome; hemophilia

33. XC Xc Xc Y EXAMPLE PROBLEM:
● A female heterozygous for normal vision: (we say she has normal vision,
but is a carrier of the colorblindness allele)
● A male who is colorblind:
XC Xc
Xc Y

34. What is the probability that:
a) they will have a son who is colorblind?
b) they will have a daughter who is colorblind?
c) their first son will be colorblind?
d) their first daughter will be carrier?
XC Xc
1/4 (25%)
1/2 (50%) Xc Y
XC Xc
Xc Xc
XC Y
Xc Y

35. XH Y XH Xh EXAMPLE PROBLEM: x
● Hemophilia is a hereditary disease in which the blood clotting process if defective. Classic hemophilia results from an abnormal or missing clotting factor VIII; it is inherited as an X-linked recessive disorder (h).
● If a man without hemophilia and a woman who is a carrier of the hemophilia allele have children, what is the probability that…
XH Y
XH Xh x

36. what is the probability that:
a) they will have a daughter with hemophilia?
b) they will have a son with hemophilia?
c) their first son will have hemophilia?
d) their first daughter will be a carrier?
XH Xh
0/4 (0%)
1/4 (25%)
1/2 (50%) XH Y
XH XH
XH Xh
XH Y
Xh Y

37. Pedigree Charts

38. Queen Victoria’s Legacy in Royal Families of Europe

40. X-inactivation in Female Mammals
● In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development
● If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

41. Two cell populations
in adult cat:
Active X
Early embryo:
Orange
fur
X chromosomes
Cell division
and X
chromosome
inactivation
Inactive X
Inactive X
Black
fur
Allele for
orange fur
Allele for
black fur
Active X

42. Tortoise-shell cats!
(a.k.a. “Torties”)
XBXb

43. So, what about the Y chromosome?

47. 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

48. 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

49. Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Gametes
n + 1
n + 1
n – 1
n – 1
n + 1
n – 1 n n
Number of chromosomes
Nondisjunction of homologous
chromosomes in meiosis I
Nondisjunction of sister
chromatids in meiosis I

50. ● Aneuploidy results from the fertilization of gametes in which nondisjunction occurred
● Offspring with this condition have an abnormal number of a particular chromosome

51. in which an organism has more than two complete sets of chromosomes
● 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

52. 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

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

54. 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

55. 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

57. 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

58. 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

59. Translocated chromosome 9
Normal chromosome 9
Reciprocal
translocation
Translocated chromosome 9
Philadelphia
chromosome
Normal chromosome 22
Translocated chromosome 22