1. The Chromosomal Basis of Inheritance
Chapter 15
The Chromosomal Basis of Inheritance
What you learned already
Chapter 13 : Meiosis and sexual life cycles
Chapter 14 : Mendel and the gene idea

2. ☞Genes ( passengers) and chromosomes ( wagon)
Overview: Locating Genes on Chromosomes
☞Genes ( passengers) and chromosomes ( wagon)
Mendel’s “hereditary factors” were genes, though this wasn’t known at the time
Today we can show that genes are located on chromosomes
Q: How to visualize that?
The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene
 Chromosomes: a physical basis for the principles of heredity (=Mendel’s laws of segregation and independent assortment)
This chapter’s aim: Is to study the chromosomal basis for the transmission of genes from parents to offspring

3. Concept 15.1: Mendelian inheritance has its physical basis in the behavior of chromosomes
Mitosis and meiosis were first described in the late 1800s
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 account for Mendel’s laws of segregation and independent assortment

4. Figure 15.2
P Generation
Yellow-round seeds (YYRR)
Green-wrinkled seeds (yyrr) Y r y  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
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
Figure 15.2 The chromosomal basis of Mendel’s laws. R r r R 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.
Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. 3 9
: 3
: 3
: 1

5. 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

6. LAW OF INDEPENDENT ASSORTMENT
Figure 15.2c
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.

7. Summary for the chromosomal basis of Mendel’s laws
Law of segregation:
Two alleles for each gene segregate during gamete formation and end up in different gametes
 Each gamete gets only one of the two alleles
 In terms of chromosomes, this segregation corresponds to the distribution of homologous chromosomes to different gamete (R or r allele; Y or y allele)
Law of independent assortment:
Alleles of genes on nonhomologous chromosomes assort independently during gamete formation
 Each gamete gets one of four allele combinations (YR:Yr:yR:yr = 1:1:1:1) depending on the alternative arrangements of homologous chromosome pairs in metaphase I

8. Morgan’s Experimental Evidence for chromosomal theory: Scientific Inquiry
Thomas Hunt Morgan (Embryologist at Columbia Univ. early in the 20th century)
Provided the first solid evidence associating a specific gene with a specific chromosome
Namely, provided convincing evidence that chromosomes are the location of Mendel’s heritable factors
Morgan’s Choice of Experimental Organism
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

9. Morgan first observed and noted : Wild type, or normal, phenotypes that were common in the fly populations
Traits alternative to the wild type: Are called mutant phenotypes
Morgan first invented a notation for symbolizing alleles in Drosophila (still widely used)
The allele for white eyes in flies is symbolized by w (indicated as a mutant allele)
A superscript + identifies the allele for the wild-type trait: w+ for the allele for red eyes

10. How to Correlate 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-eyed mutant allele must be located on the X chromosome
Morgan’s finding supported the chromosome theory of inheritance

11. Morgan’s discovery that transmission of the X chromosome in fruit flies correlates with inheritance of the eye-color trait
Was the first solid evidence indicating that a specific gene is associated with a specific chromosome
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?

12. What will you examine here How to determine sex in an organism?
성염색체 연관 유전자의 유전현상의 특징
Concept 15.2: Sex-linked genes exhibit unique patterns of inheritance
What will you examine here
We consider the role of sex chromosome in heritance
First step: reviewing the chromosomal basis of sex determination in humans and some other animals
The Chromosomal Basis of Sex (성결정과 염색체)
How to determine sex in an organism?
An organism’s sex
Is an inherited phenotypic character determined by the presence or absence of certain chromosomes (sex chromosomes)

13. In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosome
Only the ends of the Y chromosome have regions that are homologous with the X chromosome
The SRY gene on the Y chromosome codes for the development of testes

14. (d) The haplo-diploid system
Different systems of sex determination
Are found in other organisms
22 + XX X
76 + ZZ ZW 16
(Haploid)
(Diploid)
(b) The X–0 system
(c) The Z–W system
(d) The haplo-diploid system
In grasshoppers, cockroaches, there is only one type of sex chromosome (the X)
In birds, some fishes, and some insects, the sex chromosome present in the egg (not the sperm) determines the sex of offspring (Z and W)
In most species of bees and ants, there are no sex chromosomes. Female develop from fertilized eggs and are thus diploid. Males develop from unfertilized eggs and haploid (no fathers) 32
Figure 15.6b–d

15. Inheritance of Sex-Linked Genes
Key points to keep in mind
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
Sex-linked trait by recessive allele on X chromosome
Female: has two X chromosomes
Homozygous recessive alleles : expression of phenotype
Heterozygous: no expression of phenotype (called carrier)
Male: has only one X chromosome
You don’t use the terms homozygous and heterozygous: use “hemizygous”
Any male receiving the recessive allele from his mother will express the trait  far more males than females have sex-linked recessive disorders (The freq. of sex-linked recessive disorders in male is higher than that in female)

16. What kinds of X-lined disorders are found?
Some recessive alleles found on the X chromosome in humans cause certain types of disorders
Color blindness:
Duchenne muscular dystrophy : 1/3500 males born in US; progressive weakening of the muscles; the absence of a key muscle protein called dystrophin
Hemophilia: shows delayed blood clotting due to the absence of one or more of the proteins required for blood clotting; treated with intravenous injections of the missing protein

17. How do sex-lined recessive traits transmit to offspring?
XAXa
(a)
A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation.
Figure 15.7a–c

18. The transmission of sex-linked recessive traits
XaXA
(b)
If a carrier female mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder.
Figure 15.7a–c

19. The transmission of sex-linked recessive traits
XaXa
(c)
If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.
Figure 15.7a–c

20. 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
Mystery of the presence or absence of sweat glands in female skin
In humans, mosaicism can be observed in a recessive X-linked mutation that prevents the development of sweat glands
A woman who is heterozygous for this trait has patches of normal skin and patches of skin lacking sweat glands

21. Concept 15.3: 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
Location of some genes on the same chromosome is expected
The genes tend to be inherited together in genetic crosses: are said to be linked genes
The linked genes do not always follow Mendel’s law of independent assortment

22. 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

23. However, nonparental phenotypes were also produced
The production of a small number of offspring with nonparental phenotypes indicated that some mechanism occasionally breaks the linkage between genes on the same chromosome
Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent
Figure 15.UN01 In-text figure, p. 294

24. Genetic Recombination and Linkage
What you learned in the Chapter 13
Meiosis and random fertilization generate genetic variation among offspring of sexually reproducing organisms
The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination
What will you examine next
What is the chromosomal basis of recombination in relation to the genetic findings of Mendel and Morgan?

25. 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

26. Recombination of Linked Genes: Crossing Over
Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed
He proposed that some process must occasionally break the physical connection between genes on the same chromosome
That mechanism was the crossing over of homologous chromosomes

27. Figure 15.10
Testcross parents
Replication of chromosomes
Gray body, normal wings (F1 dihybrid)
Black body, vestigial wings (double mutant)
Meiosis I
Meiosis II
Meiosis I and II
Recombinant chromosomes
Eggs
b vg
b vg
b vg
b vg
b vg
b vg
bvg
Testcross offspring
965 Wild type (gray-normal)
944 Black- vestigial
206 Gray- vestigial
185 Black- normal
Sperm
Parental-type offspring
Recombinant offspring
Recombination frequency
391 recombinants 2,300 total offspring
  17% 
Chromosomal basis for recombination of linked genes: Linked genes exhibit RF less than 50%
Figure Chromosomal basis for recombination of linked genes.

28. Gray body, normal wings (F1 dihybrid)
Figure 15.10a
Testcross parents
Gray body, normal wings (F1 dihybrid)
Black body, vestigial wings (double mutant)
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
Meiosis I: Crossing
over between b and vg
loci produces new allele
combinations.
b vg
b vg
b vg
Meiosis I and II:
Even if crossing over
occurs, no new allele
combinations are
produced.
b vg
Meiosis II: Segregation
of chromatids produces
recombinant gametes
with the new allele
combinations.
Figure Chromosomal basis for recombination of linked genes.
b vg
b vg
Recombinant chromosomes
bvg
b vg
b vg
b vg
b vg
Eggs
Sperm

29. Recombinant chromosomes
Figure 15.10b
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
b vg
b vg
b vg
b vg
Figure Chromosomal basis for recombination of linked genes.
Sperm
Parental-type offspring
Recombinant offspring
Recombination frequency
391 recombinants 2,300 total offspring 
  17%
RF: the percentage of recombinants in the total offspring

30. Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry
Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome
Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency
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

31. How to construct a linkage map
Example
Consider three genes: the body-color (b), wing-size (vg), and cinnabar eyes (cn) [brighter red than wt eye color]
The observed recombination frequencies between three Drosophila gene pairs : b–cn 9%, cn–vg 9.5%, and b–vg 17%
Make a linear order : cn is positioned about halfway between the other two genes:
Chromosome
Recombination frequencies 9%
9.5%
17% b cn vg
RESULTS
b, black body color
vg, vestigial wing
cn, cinnabar eyes
1st cross-over
2nd CO
Figure 15.11

32. How to construct a linkage map (continued)
Example
Inquiry: The b–vg recombination frequency (17%) is slightly less than the sum (18.5%) of the b–cn and cn–vg frequencies. Why?
Because double crossovers are fairly likely to occur between b and vg in matings tracking these two genes.
A second crossover would “cancel out” the effect of the first crossover and thus reduce the observed b–vg RF.

33. Canceling out of the effect of the 1st crossover by 2nd cross-over

34. 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
Sturtevant used recombination frequencies to make linkage maps of fruit fly genes
Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes
Cytogenetic maps indicate the positions of genes with respect to chromosomal features

35. Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders
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

36. 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

37. The consequences of nondisjunction after fertilization?
Aneuploidy
Results from the fertilization of aberrant gametes (nondisjunction occurred) with a normal one
Is a condition in which offspring have an abnormal number of a particular chromosome
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
Chromosome number of haploid (gamete): n
Chromosome number of normal zygote: 2n
If a zygote is trisomic (2n+1 chromosomes)
It has three copies of a particular chromosome
If a zygote is monosomic (2n-1 chromosomes)
It has only one copy of a particular chromosome

38. 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

39. 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
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, a correlation that has not been explained

40. 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

41. 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
Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes

42. Concept 15.5: Some inheritance patterns are exceptions to the standard chromosome theory
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
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 (Monoallelic expression)
Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production

43. Genomic imprinting
Involves the silencing of certain genes that are “stamped” with an imprint during gamete production
A zygote expresses only one allele of an imprinted gene (either from the mother or the father)
 The imprints are transmitted to all the body cells during development
A gene imprinted for maternal allele expression is always imprinted for maternal allele expression, generation to generation

44. Genomic imprinting of the mouse Igf2 gene.
Figure 15.17a
Genomic imprinting of the mouse Igf2 gene.
Figure Genomic imprinting of the mouse Igf2 gene.

45. 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 (see next slide)