1. The Chromosomal Basis of Inheritance
Chapter 15
The Chromosomal Basis of Inheritance

2. Overview: Locating Genes Along Chromosomes
Mendel’s “hereditary factors” were genes, though this wasn’t known at the time
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
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3. 1. What is the chromosomal theory of inheritance?
Mitosis and meiosis were first described in the late 1800s
The chromosomal theory of inheritance states:
Mendelian genes have specific loci (positions) on chromosomes
Chromosomes undergo segregation and independent assortment
The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment
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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. 2. Why did Morgan choose drosophila for his research
2. Why did Morgan choose drosophila for his research? Distinguish between wild type and mutant phenotypes. What did his work eventually find a correlation between?
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
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6. Morgan’s Choice of Experimental Organism (Studyguide Question 2)
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
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7. Traits alternative to the wild type are called mutant phenotypes
Morgan noted wild type, or normal, phenotypes that were common in the fly populations
Traits alternative to the wild type are called mutant phenotypes
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8. Morgan’s finding supported the chromosome theory of inheritance
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-eyed mutant allele must be located on the X chromosome
Morgan’s finding supported the chromosome theory of inheritance
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9. The Chromosomal Basis of Sex (Studyguide Question 3)
In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosome
The SRY gene on the Y chromosome codes for the development of testes (sex determining region of Y)
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10. Fig. 15-5 X Y
Figure 15.5 Human sex chromosomes

11. Inheritance of Sex-Linked Genes (Studyguide Question 4)
The sex chromosomes have genes for many characters unrelated to sex
A gene located on either sex chromosome is called a sex-linked gene – usually associated with the X chromosome.
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
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12. Some disorders caused by recessive alleles on the X chromosome in humans:
Color blindness
Duchenne muscular dystrophy
Hemophilia
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13. The inactive X condenses into a Barr body
5. Describe the process of X-inactivation. What is a Barr body? Describe an example of a disorder in humans that might relate to this process.
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
Lyon’s Disease
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14. 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

15. 6. What are 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
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
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16. 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
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17. Abnormal Chromosome Number Studyguide Question 7)
In nondisjunction, pairs of 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
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18. Meiosis I Meiosis II (a) Nondisjunction of homologous
Fig
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Figure Meiotic nondisjunction
(a) Nondisjunction of homologous
chromosomes in meiosis I
(b) Nondisjunction of sister
chromatids in meiosis II

19. A monosomic zygote has only one copy of a particular chromosome
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
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20. Polyploidy is common in plants, but not animals
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
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21. What’s up with this rodent?
Fig
What’s up with this rodent?
Figure A tetraploid mammal

22. Studyguide question 8
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
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23. 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

24. 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
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25. 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 (but most likely has nothing to do with the age of the eggs)
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26. Fig
Figure Down syndrome

27. Age vs. Incidence of Down Syndrome

28. 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
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30. Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans

31. 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
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32. Translocated chromosome 22 (Philadelphia chromosome)
Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes
People with CML have an abnormal chromosome called the Philadelphia chromosome (Ph chromosome). The Ph chromosome is the result of a translocation between chromosomes 22 and 9. The translocation leads to the development of a cancer-causing gene (oncogene) called the BCR-ABL gene.
The BCR-ABL oncogene gives a stem cell instructions to make a dysfunctional protein called BCR-ABLtyrosine kinase, which leads to the development of CML.
Figure Translocation associated with chronic myelogenous leukemia (CML)
Reciprocal
translocation
Normal chromosome 9
Translocated chromosome 9
Translocated chromosome 22
(Philadelphia chromosome)
Normal chromosome 22

33. 10. What are extranuclear genes (cytoplasmic genes)?
Extranuclear genes (or cytoplasmic genes) are genes 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
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34. Fig
Figure Variegated leaves from Croton dioicus

35. 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
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36. You should now be able to:
Explain the chromosomal theory of inheritance and its discovery
Explain why sex-linked diseases are more common in human males than females
Distinguish between sex-linked genes and linked genes
Explain how meiosis accounts for recombinant phenotypes
Explain how linkage maps are constructed
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37. Explain how nondisjunction can lead to aneuploidy
Define trisomy, triploidy, and polyploidy
Distinguish among deletions, duplications, inversions, and translocations
Explain genomic imprinting
Explain why extranuclear genes are not inherited in a Mendelian fashion
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