THE CHROMOSOMAL
BASIS OF INHERITANCE
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A. Background
1. Genetics
1860’s—Mendel proposed that discrete inherited factors
segregate and assort independently during gamete
formation
2. Cytology
1875—Cytologists worked out process of mitosis
1890’s—Cytologists worked out process of meiosis
3. Genetics
1900—Correns, von Tschermak, and de Vries
independently discovered Mendel’s work
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4. Cytology and Genetics
1902—2 areas converge as Walter Sutton, Theodor Boveri,
and others noticed parallels between the behavior of
Mendel’s factors and the behavior of chromosomes:
 Chromosomes and genes both present in pairs in
diploid cells.
 Homologous chromosomes separate and allele pairs
segregate during meiosis.
 Fertilization restores the diploid condition for both.
5. Chromosomal Theory of Inheritance is based on these
observations. According to this theory:
 Mendelian factors (genes) are located on chromosomes.
 Chromosomes segregate and assort independently
during meiosis
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1. Walter Flemming (1882)
 First to observe chromosomes in nuclei of dividing
salamander cells
 Called process “mitosis”
2. August Weismann (1887)
 Each gamete has half the number of chromosomes as a
fertilized egg.
 Proposed that a special division process reduced the
chromosome number by one half
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3. Theodore Boveri (1888)
 Determined that chromosomes were essential for fertilization
and development
 Discovered the centriole
 Actually observed meiosis in cells of Ascaris
4. Walter Sutton (1902)
Found relationship between meiosis and Mendel’s laws
Predicted gene linkage
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5. Thomas Hunt Morgan (1910)
 Began experiments with Drosophila melanogaster (fruit fly)
 Discovered X-linked (sex linked) inheritance
 Discovered sex determination (X and Y chromosomes)
 Provided convincing evidence that Mendel’s factors are
located on chromosomes
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1. Reasons for using Drosophila
 Easy to raise
 Produce a large number of offspring
 Short life cycle (2 weeks)
 Mutants easily recognized
 Only 4 pairs of chromosomes (3 pr. of autosomes, 1 pr.
of sex chromosomes XX female, XY male)
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2. Sex-linked Traits
 Wild type—normal character phenotype
Ex: w+-red eyes
 Mutant phenotype
-alternatives to wild type
-due to mutations in wild type gene
Ex: w-white eyes
 Discovered by Morgan
 Refers to genes on the X chromosome
 From this experiment, Morgan deduced that:
a. Eye color is linked to sex.
b. The gene for eye color is located on the X chromosome.
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Fig. 15-4b
EXPERIMENT
P
Generation
F1
Generation
RESULTS
F2
Generation

All offspring
had red eyes

Experiment:
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3. Morgan’s finding of the correlation between a particular trait
and an individual’s sex provided support for the chromosome
theory of inheritance
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Heterogametic sex—produces 2 kinds of gametes which
determine the sex of offspring
 Homogametic sex—produces 1 kind of gamete with respect
to sex chromosome
 In humans and some other animals, there is a chromosomal
basis of sex determination
 Each gamete has only 1 sex chromosome.

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A. The Chromosomal Basis of Sex
1.In humans and other mammals, there are two varieties
of sex chromosomes: a larger X chromosome and a
smaller Y chromosome
2.Only the ends of the Y chromosome have regions that
are homologous with the X chromosome
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A.

The Chromosomal Basis of Sex
3. The SRY gene on the Y chromosome codes for the
development of testes
SRY- Sex determining Region of Y
◦ -The presence of this gene on the Y chromosome
◦ codes for the development of testes. In the absence of
◦ this gene, the gonads develop into ovaries
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B. Systems of Sex Determination
1. X-Y
 Mammals, humans, Drosophila
 ♂--heterogametic (XY)
 ♀--homogametic (XX)
 Y chromosome determines sex of offspring
2. X-O
 Grasshopper, cricket, roach, and other insects
 ♂--heterogametic (XO)
 ♀--homogametic (XX)
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3. Z-W
Birds, some fish, some insects—butterflies and moths
♀--heterogametic (ZW)
♂--homogametic (ZZ)
4. Haplo-diploidy
 Bees and ants
 Have no sex chromosomes
 ♀--develops from fertilized egg (2n)
 ♂--develops parthenogenetically from unfertilized egg (n)
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C. Inheritance of Sex-Linked Genes
1. The sex chromosomes have genes for many characters
unrelated to sex
2. A gene located on the X chromosome is called a sexlinked gene
3. Genes on the Y chromosome are called holandric genes
and are found in males only
4. In humans, sex-linked usually refers to a gene on the
larger X chromosome
5. Sex-linked genes follow specific patterns of inheritance
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6. 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
7. Sex-linked recessive disorders are much more common in
males than in females
8. If a sex-linked trait is due to a recessive allele, a female
will express the trait only if she is homozygous.
9. A heterozygous female is a carrier.
10. Males only need 1 allele of a sex-linked trait to show the
trait.
11. Males are hemizygous (only one copy of a gene is
present in a diploid organism)
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Fig. 15-7
N= normal color vision
XNXN

Xn Y
XNXn

XNY
XNXn

Xn Y
12. Fathers pass sex-linked
alleles to only and all of
their daughters
XA—Normal gene
Xa—Sex-linked gene
XAXA—Normal Female
XAXa—Carrier Female
XaXa—Affected Female
XAY—Normal Male
XaY—Affected Male
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13. Mothers can pass sexlinked alleles to both sons
and daughters.
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14. 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, whereas males
without the disorder will
be completely free of the
recessive allele
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a. Color Blindness
-recessive
-can’t distinguish certain colors
-red-green most common
b. Duchenne’s Muscular Dystrophy
-recessive
-atrophy of muscle
c. Hemophilia
-recessive
-blood fails to clot because of lack of a clotting factor
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1. Female mammals have only one fully functional X
chromosome in diploid cells.
2. Proposed by Mary F. Lyon and known as the Lyon
Hypothesis
3. Each of the embryonic cells inactivates one of the two X
chromosomes.
4. Inactive X contracts into densely staining object called a
Barr Body.
5. Ex:
Mosaic coloration of calico cats
Normal sweat gland development in humans
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1. Sex-limited Traits
◦ Appear exclusively in one sex
◦ Ex: uterine cancer in ♀; prostate cancer in ♂
2. Sex-influenced Traits
◦ Expression is influenced by presence of ♀ or ♂ sex
hormones
◦ Acts as a dominant in one sex and recessive in the other
◦ Ex: ♂--baldness, stomach ulcers;
♀--breast cancer
both—length of index finger as compared to ring finger
-dominant in ♂ shorter index finger
-dominant in ♀ longer index finger
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



Each chromosome has hundreds or thousands of genes
Genes located on the same chromosome that tend to be
inherited together are called linked genes
Do not assort independently
Dihybrid crosses deviate from expected 9:3:3:1 phenotypic
ratio
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A. Genetic Recombination
1. Production of offspring with new combinations of traits
different from those combinations found in the parents
(crossing over)
2. Results from the events of meiosis and random fertilization
B. Recombination of Unlinked Genes: Independent Assortment
Parental types—progeny that have the same phenotype as
one or the other of the parents
Recombinant types—progeny whose phenotypes differ from
either parent
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Parental Types- offspring that inherit a phenotype that matches
one of the parental phenotypes.
Gametes from yellow-round
heterozygous parent (YyRr)
Gametes from greenwrinkled homozygous
recessive parent ( yyrr)
YR
yr
Yr
yR
YyRr
yyrr
Yyrr
yyRr
yr
Parentaltype
offspring
Recombinant
offspring
Recombinant Types or Recombinants- offspring that have new
combinations of phenotypes.
P
F1


Yy Rr
x
(yellow, round)
¼ YyRr
¼ yyrr
¼ yyRr
¼ Yyrr
yyrr (testcross)
(green, wrinkled)
Parental types
50%
Recombinant types 50%
When half the progeny are recombinants, there is a 50%
frequency of recombination.
A 50% frequency of recombination usually indicates that the
two genes are on different chromosomes, because it is the
expected result if the two genes assort randomly.
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b—black body
b+--gray body
b+ b vg+ vg
(gray, normal wings)
vg—vestigial wings
vg+--wild type wings
x
b b vg vg (testcross)
(black, vestigial wings)
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b vg
b vg+ b b vg+vg
Phenotypes
Expected
if genes not
linked
Expected if Actual
genes
totally
linked
black
normal
575
0
206
b+ vg+ b+ b vg+vg gray
normal
575
1150
965
b vg
b b vg vg black
vestigial
575
1150
944
b+ vg
b+ b vg vg gray
vestigial
575
0
185
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What type of ratios would you expect to see in the testcross
offspring if the genes were located on different chromosomes?
What if they were located on the same chromosome and parental
alleles are always inherited together?
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






Recombination Frequency (RF) = # recombinants x 100
total # offspring
Proposed by Morgan
Process of crossing over during meiosis accounts for the
recombination of linked genes (genes on same chromosome)
Crossing over—breakage and exchange of corresponding
segments between homologous chromosomes
--results in new allelic combination
Probability of crossing over (recombination) between two
genes is proportional to the distance separating those genes
The closer together two genes are, the less likely that a cross
over will occur.
Proved by A. H. Sturtevant
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1. Recombination frequencies are used to construct
chromosome maps [show locations of genes on a particular
chromosome (linear)]
2. Sturtevant constructed chromosome maps for Drosophila using
recombination frequencies
3. 1 map unit = 1% recombination frequency (now called
centimorgans)
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

Genetic Map- an ordered list of the genetic loci
along a particular chromosome.
Linkage Map- a genetic map based on
recombination frequencies. Displays order but not
precise location.
◦ Distances are expressed in map units- equivalent to 1%
recombination frequency. (Centimorgans)
4. How to use XO (crossover) data to construct a chromosome map:
 Ex:
RF
b vg
17%
cn b
9%
cn vg
9.5%
a. Establish the distance between the genes with the
highest RF
b-----17------------vg
b. Determine RF between third gene and first.
cn----9-----b
c. Consider the two possible placements of the third gene.
cn----9-----b--------17---------vg
or
b---9------cn---8-----vg
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d.
Determine the RF between the third gene and the second
gene to eliminate the incorrect sequence
b---9------cn-----9.5-----vg
17
--correct sequence b-cn-vg
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5. If linked genes are so far apart on a chromosome that the RF is
50%, they are indistinguishable from unlinked genes that assort
independently.
 Can map such genes if RF can be determined between those
two genes and intermediate genes.
6. Maps from XO data give relative positions of linked genes
7. Cytological mapping pinpoints actual location of genes and real
distance between them.
 May differ from XO maps in distance but not sequence.
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Large-scale chromosomal alterations often lead to
spontaneous abortions (miscarriages) or cause a variety of
developmental disorders
 Meiotic errors and mutagens can cause major
chromosomal changes such as altered chromosome
numbers or altered chromosomal structure.
A. Alterations of Chromosomal Number
1. Nondisjunction
 In nondisjunction, pairs of homologous chromosomes
do not separate normally during meiosis
 Results in one gamete receiving two of the same type
of chromosome (n+1) and the other gamete receiving
none (n-1)

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2. 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 chromosomal aberration in which one or more
chromosomes are present in extra copies or deficient
in number
 A monosomic
zygote has only one copy of a particular
chromosome
 A trisomic zygote has three copies of a particular
chromosome
 Ex: Down’s Syndrome or Trisomy 21
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3. Polyploidy
 Polyploidy is a condition in which an organism has more
than two complete sets of chromosomes
◦ a chromosomal alteration in which the organism
possesses more than two complete chromosome sets.
 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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1. Breakage of a chromosome can lead to four types of
changes in chromosome structure:
a. Deletion removes a chromosomal segment
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b. Duplication repeats a segment
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c. An inversion occurs if the fragment reattaches to the
original chromosome in reverse order.
Inversion reverses a segment within a chromosome
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d. A translocation occurs if a chromosomal fragment joins to
a nonhomologous chromosome
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2. Crossing over can produce deletions or duplicatons.
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C. Chromosomal Alterations in Human Disease
1. Alterations of chromosome number and structure are
associated with some serious disorders
2. Some types of aneuploidy appear to upset the genetic balance
less than others, resulting in individuals surviving to birth and
beyond
3. These surviving individuals have a set of symptoms, or
syndrome, characteristic of the type of aneuploidy
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4. Examples of Autosomal Aneuploidy:
a. Down’s Syndrome
 Trisomy 21
 Related to age of parent
 Most common birth defect in U. S. (1/700 births)
b. Patau Syndrome
 Trisomy 13
c. Edward’s Syndrome
 Trisomy 18
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5. Examples of Sex Chromosome Aneuploidy: (less severe)
a. Klinefelter’s Syndrome--Genotype usually XXY
b. Extra Y--XYY
c. Trisomy X (metafemales)--XXX
d. Turner’s Syndrome (monosomy X)--XO
6. Examples of Deletions:
a. Cri du chat Syndrome--Deletion on chromosome 5
7. Examples of Translocations:
a. Chronic Myelogenous Leukemia (CML)--Portion of
chromosome 22 switched with a fragment of
chromosome 9
b. Type of Down’s Syndrome--Translocation from
chromosome 21 to chromosome 15
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

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
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A. Genomic Imprinting
1. For a few mammalian traits, the phenotype depends on
which parent passed along the alleles for those traits
2. Such variation in phenotype is called genomic imprinting
3. Genomic imprinting involves the silencing of certain genes
that are “stamped” with an imprint during gamete
production
4. “a variation in phenotype depending on whether
an allele is inherited from the male or female
parent.
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4. It appears that imprinting is the result of the methylation
(addition of –CH3) of DNA
5. Genomic imprinting is thought to affect only a small
fraction of mammalian genes
6. Most imprinted genes are critical for embryonic development
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B. Inheritance of Organelle Genes
1. Extranuclear genes (or cytoplasmic genes) are genes
found in organelles in the cytoplasm
2. Mitochondria, chloroplasts, and other plant plastids carry
small circular DNA molecules
3. Extranuclear genes are inherited maternally because the
zygote’s cytoplasm comes from the egg
4. The first evidence of extranuclear genes came from
studies on the inheritance of yellow or white patches on
leaves of an otherwise green plant
5. Some defects in mitochondrial genes prevent cells from
making enough ATP and result in diseases that affect the
muscular and nervous systems
6. Cytoplasmic genes described in plants by Karl Correns
(1909)
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1. Explain the chromosomal theory of inheritance and its
discovery
2. Explain why sex-linked diseases are more common in
human males than females
3. Distinguish between sex-linked genes and linked genes
4. Explain how meiosis accounts for recombinant
phenotypes
5. Explain how linkage maps are constructed
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6. Explain how nondisjunction can lead to aneuploidy
7. Define trisomy, triploidy, and polyploidy
8. Distinguish among deletions, duplications, inversions, and
translocations
9. Explain genomic imprinting
10. Explain why extranuclear genes are not inherited in a
Mendelian fashion
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