1. Chromosomal Basis of Inheritance
Biology 112

2. Locating Genes Along Chromosomes
Mendel’s “hereditary factors” were genes, though this wasn’t known during his time
Today know 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:
Mendelian inheritance has its physical basis in the behavior of chromosomes
The chromosome theory of inheritance states:
Mendelian genes have specific loci (positions) on chromosomes
Chromosomes undergo segregation and independent assortment
The behavior of chromosomes during meiosis can be said to account for Mendel’s laws of segregation and independent assortment

4. Figure 15.2 The chromosomal basis of Mendel’s laws
P Generation
Yellow-round
seeds (YYRR)
Green-wrinkled
seeds ( yyrr) Y y  r Y R 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
LAW OF SEGREGATION
The two alleles for each gene
separate during gamete
formation.
Meiosis
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
Figure 15.2 The chromosomal basis of Mendel’s laws R r
Metaphase II r R 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
F2 Generation
An F1  F1 cross-fertilization 3 3 9
: 3
: 3
: 1

5. Drosophila melanogaster
Thomas Hunt Morgan
Drosophila melanogaster

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

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

8. Sex-Linked Genes Sex-Linked genes: Genes located on sex chromosomes.
This term is commonly applied to genes on the X chromosome
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-eyed mutant allele must be located on the X chromosome

9. EXPERIMENT RESULTS CONCLUSION Fig. 15-4 + w w + w w + +
Generation F1
All offspring had red eyes
Generation
RESULTS F2
Generation
CONCLUSION P + X w X w
Generation X  Y + w w
Sperm
Eggs F1 + +
Figure 15.4 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 w
Generation w w + w
Sperm
Eggs + + + w w F2 w
Generation + w w w w + w

10. Linked genes Each chromosome has hundreds or thousands of genes
Genes located on the same chromosome that tend to be inherited together are called linked genes
Linked genes tend to be inherited together because they are located near each other on the same chromosome

11. Linkage Affects Inheritance
Morgan did some 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

12. However, nonparental phenotypes were also produced
Morgan found that body color and wing size are usually inherited together in specific combinations (parental phenotypes)
He noted that these genes do not assort independently, and reasoned that they were on the same chromosome
However, nonparental phenotypes were also produced
Genetic recombinationoccured: the production of offspring with combinations of traits differing from either parent

13. b+ vg+ b vg  Parents in testcross b vg b vg b+ vg+ b vg Most or
Fig. 15-UN1
b+ vg+
b vg 
Parents
in testcross
b vg
b vg
b+ vg+
b vg
Most
offspring or
b vg
b vg

14. EXPERIMENT RESULTS Fig. 15-9-4 P Generation (homozygous) b+ b+ vg+ vg+
Wild type
(gray body,
normal wings)
Double mutant
(black body,
vestigial 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 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

15. Recombination of Unlinked Genes: Independent Assortment of Chromosomes
Mendel observed that combinations of traits in some offspring differ from either parent
Offspring with a phenotype matching one of the parental phenotypes are called parental types
Offspring with nonparental phenotypes (new combinations of traits) are called recombinant types, or recombinants
A 50% frequency of recombination is observed for any two genes on different chromosomes

16. 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

17. Black body, vestigial wings
Fig
Testcross
parents
Gray body, normal wings
(F1 dihybrid)
Black body, vestigial wings
(double mutant)
b+ vg+
b vg
b vg
b vg
Replication
of chromo-
somes
Replication
of chromo-
somes
b+ vg+
b vg
b+ vg+
b vg
b vg
b vg
b vg
b vg
Meiosis I
b+ vg+
Meiosis I and II
b+ vg
b vg+
b vg
Meiosis II
Recombinant
chromosomes
Figure Chromosomal basis for recombination of linked genes
b+ vg+
b vg
b+ vg
b vg+
Eggs
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 =
 100 = 17%
2,300 total offspring

18. Black body, vestigial wings
Fig a
Testcross
parents
Gray body, normal wings
(F1 dihybrid)
Black body, vestigial wings
(double mutant)
b+ vg+
b vg
b vg
b vg
Replication
of chromo-
somes
Replication
of chromo-
somes
b+ vg+
b vg
b+ vg+
b vg
b vg
b vg
b vg
b vg
Meiosis I
b+ vg+
Meiosis I and II
b+ vg
b vg+
Figure Chromosomal basis for recombination of linked genes
b vg
Meiosis II
Recombinant
chromosomes
b+ vg+
b vg
b+ vg
b vg+
b vg
Eggs
Sperm

19. 965 944 Black- vestigial 206 Gray- vestigial 185 Black- normal
Fig b
Recombinant
chromosomes
b+ vg+
b vg
b+ vg
b vg+
Eggs
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+
Figure Chromosomal basis for recombination of linked genes
b vg
b vg
b vg
b vg
Sperm
Parental-type offspring
Recombinant offspring
Recombination
frequency
391 recombinants =
 100 = 17%
2,300 total offspring

20. Mapping the Distance Between Genes Using Recombination Data
Genetic map, an ordered list of the genetic loci along a particular chromosome
The farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency

21. 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

22. RESULTS Recombination frequencies 9% 9.5% Chromosome 17% b cn vg
Fig
RESULTS
Recombination
frequencies 9%
9.5%
Chromosome
17%
Figure Constructing a linkage map b cn vg

23. Mutant phenotypes Short aristae Black body Cinnabar eyes Vestigial
Fig
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

24. 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

25. Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes
Cytogenetic maps indicate the positions of genes with respect to chromosomal features

26. Sex systems in animals

27. Figure 15.6 Some chromosomal systems of sex determination
44 + XY
44 + XX
Parents
22 + X
22 + Y
22 + X or +
Sperm
Egg
44 + XX
44 + XY or
Zygotes (offspring)
(a) The X-Y system
22 + XX
22 + X
(b) The X-0 system
76 + ZW
76 + ZZ
Figure 15.6 Some chromosomal systems of sex determination
(c) The Z-W system 32
(Diploid) 16
(Haploid)
(d) The haplo-diploid system

28. 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
In humans, sex-linked usually refers to a gene on the larger X chromosome

29. Sex-linked genes follow specific patterns of inheritance
For a recessive sex-linked trait to be expressed
A female needs two copies of the allele
A male needs only one copy of the allele
Sex-linked recessive disorders are much more common in males than in females
Some disorders caused by recessive alleles on the X chromosome in humans:
Color blindness
Duchenne muscular dystrophy
Hemophilia

30. (a) (b) (c) Sperm Sperm Sperm Eggs Eggs Eggs XNXN  XnY XNXn  XNY
Fig. 15-7
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
Figure 15.7 The transmission of sex-linked recessive traits
(a)
(b)
(c)

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

32. 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
DNA Methylation is the mechanism for X-inactivation
(methyl groups added to cytosine nucleotide in the DNA molecule)

33. X chromosomes Allele for orange fur Early embryo: Allele for black fur
Fig. 15-8
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

34. Chromosomal Alterations
Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders…bad news!

35. 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
Nondisjunction can also occur in mitosis

36. Meiosis I Meiosis II Gametes (a) Nondisjunction of homologous
Fig
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Gametes
Figure Meiotic nondisjunction
n + 1
n + 1
n – 1
n – 1
n + 1
n – 1 n n
Number of chromosomes
(a) Nondisjunction of homologous
chromosomes in meiosis I
(b) Nondisjunction of sister
chromatids in meiosis II
Nondisjunction video

37. Aneuploidy
Aneuploidy results from the fertilization of gametes in which nondisjunction occurred
Offspring with this condition have an abnormal number of a particular chromosome
A monosomic zygote has only one copy of a particular chromosome
A trisomic zygote has three copies of a particular chromosome

38. Polyploidy
Polyploidy is a condition in which an organism has more than two complete 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

39. 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

40. Reciprocal translocation
Fig
A B C D E F G H
A B C E F G H
Deletion
(a)
A B C D E F G H
A B C B C D E F G H
Duplication
(b)
A B C D E F G H
A D C B E F G H
(c)
Inversion
Figure Alterations of chromosome structure
A B C D E F G H
M N O C D E F G H
(d)
Reciprocal
translocation
M N O P Q R
A B P Q R

41. 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

42. Down Syndrome (Trisomy 21)
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.

43. Aneuploidy of Sex Chromosomes
Nondisjunction of sex chromosomes produces a variety of aneuploid conditions
Males
Klinefelter syndrome is the result of an extra chromosome in a male, producing sterile XXY individuals (1 in 2000 births?)
Extra Y (XYY)…apparently normal males (1 in 1000 births?)
Females
Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans (1 in births?)
Triple X Syndrome (XXX)…apparently normal females (1 in births?)

44. 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
Causes certain genes to be differently expressed in the offspring depending upon whether the alleles were inherited from the ovum or from the sperm cell.

45. Fragile-X syndrome (CGG) Huntington’s disease (CAG)
Triplet Repeats
Fragile-X syndrome (CGG)
Huntington’s disease (CAG)

46. Extranuclear Genes
Extranuclear genes (or cytoplasmic genes) are genes found in organelles in the cytoplasm
Mitochondria, chloroplasts carry small circular DNA molecules
Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg