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Chapter 15
The Chromosomal Basis of
Inheritance
• Overview: Locating Genes on Chromosomes
• Genes
– Are located on chromosomes
Figure 15.1
Mendelian inheritance has its physical basis in
the behavior of chromosomes
• Several researchers proposed in the early 1900s
that genes are located on chromosomes
• The behavior of chromosomes during meiosis
was said to account for Mendel’s laws of
segregation and independent assortment
What does the chromosome theory of inheritance state?
– Genes occupy specific positions on chromosomes
– Chromosomes undergo segregation and
independent assortment in the process of meiosis in
gamete formation
The chromosomal basis of Mendel’s Laws
P Generation
Starting with two true-breeding pea plants,
we follow two genes through the F1 and F2
generations. The two genes specify seed
color (allele Y for yellow and allele y for
green) and seed shape (allele R for round
and allele r for wrinkled). These two genes are
on different chromosomes. (Peas have seven
chromosome pairs, but only two pairs are
illustrated here.)
Yellow-round
seeds (YYRR)
Green-wrinkled
seeds (yyrr)
Y
R
Y
r
R
y
r
y
Meiosis
Fertilization
y
R Y
Gametes
r
All F1 plants produce
yellow-round seeds (YyRr)
R
R
y
F1 Generation
y
r
r
Y
Y
Meiosis
The two alleles
for each gene
separate during
gamete formation
LAW OF SEGREGATION
r
R
Y
1 The R and r alleles segregate
R
at anaphase I, yielding
two types of daughter
cells for this locus.
Y
y
y
Anaphase I
y
Y
1 Alleles at both loci segregate
in anaphase I, yielding four
R
types of daughter cells
depending on the chromosome
arrangement at metaphase I.
Compare the arrangement of
the R and r alleles in the cells
y
on the left and right
r
R
y
y
Metaphase II
Y
y
Y
Y
R
R
r
Y
r
r
1 yr
4
F2 Generation
3 Fertilization
recombines the
R and r alleles
at random.
Y
Y
r
1
YR
4
Figure 15.2
Y
LAW OF INDEPENDENT ASSORTMENT
r
r
Y
Gametes
R
r
R
2 Each gamete
gets one long
chromosome
with either the
R or r allele.
Two equally
probable
arrangements
of chromosomes
at metaphase I
r
1 yr
4
2 Each gamete gets
a long and a short
chromosome in
one of four allele
combinations.
y
y
R
R
1
yR
4
Fertilization among the F1 plants
9
:3
:3
:1
3 Fertilization results
in the 9:3:3:1
phenotypic ratio in
the F2 generation.
Alleles of genes
on
nonhomologous
chromosomes
assort
independently
during gamete
formation.
Morgan’s Experimental Evidence: Scientific Inquiry
• Thomas Hunt Morgan
– Provided convincing evidence that chromosomes
are the location of Mendel’s heritable factors
Morgan’s Choice of Experimental
Organism
• Morgan worked with fruit flies
– Because they breed at a high rate
– A new generation can be bred every two weeks
– They have only four pairs of chromosomes
What Morgan Discovered
• Morgan first observed and noted
– Wild type, or normal, phenotypes that were
common in the fly populations – like red eyes
• Traits alternative to the wild type
– Are called mutant phenotypes – like white eyes
Figure 15.3
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 (phenotype) the 3:1
red:white eye ratio, but only males had white
eyes
• Genotype
– w+w+ w+w w+Y wY
• Morgan determined
– That the white-eye mutant allele must be located
on the X chromosome
EXPERIMENT Morgan mated a wild-type (red-eyed) female
with a mutant white-eyed male. The F1 offspring all had red eyes.
P
Generation
X
F1
Generation
Morgan then bred an F1 red-eyed female to an F1 red-eyed male to
produce the F2 generation.
RESULTS
The F2 generation showed a typical Mendelian
3:1 ratio of red eyes to white eyes. However, no females displayed the
white-eye trait; they all had red eyes. Half the males had white eyes,
and half had red eyes.
F2
Generation
Figure 15.4
• Morgan’s discovery
– Was the first solid evidence indicating that a specific
gene is associated with a specific chromosome
Sex-linked Genes
• Inheritance associated with the sex
chromosomes
– Many genes are found on the X chromosome
– The Y chromosome is much smaller and carries
only a few genes
Inheritance of sex-linked genes
• Males inherit their sex linked alleles from only
their mothers
• Daughters inherit sex linked alleles from both
parents.
• Males show more recessive sex linked traits
since they are hemizygous (having or characterized by one or
more genes (as in a genetic deficiency or in an X chromosome paired with a Y
chromosome) that have no allelic counterparts)
genes
— for sex-linked
• Sex-linked disorders (carried on the X
chromosome) can be recessive or dominant
• Because males have just one X chromosome they
will express the trait even if it is recessive.
• Females have 2 X chromosomes, so in order for
them to express a recessive trait they must get
two copies of the recessive allele.
Sex-linked disorders -Colorblindness
• An inability to distinguish certain colors
– Red-green colorblindness is found in about 1 in 10
males.
– In females it is rare - only about 1 in 100 has
colorblindess
• Why?
• It is recessive, and a female would have to get 2 copies
of the allele to express the trait.
Sex linked disorders - Hemophilia
• Blood does not clot properly
• Affects about 1 in 5,000 to 1 in 25,000 males
depending on the type of hemophilia.
– Woman rarely suffer from severe hemophilia, but
carries can have bleeding problems.
Sex linked disorders - Duchenne Muscular Dystrophy
• Rapid progressive weakening and loss of
skeletal muscle early in life.
• Most die by age 30 (some have lived into their
40’s and 50’s)
• Affects 1 in 3,500 males
X Inactivation in Female Mammals
• Inactivation of one of the X chromosomes
in females. Leaves a dark stained body at
the membrane. Called a Barr Body
• This way, all cells of females and males
function the same way. Inactivation is
random.
The selection of which X chromosome is inactivated is a random event, as seen here.
• If a female is heterozygous for a particular gene
located on the X chromosome
– She will be a mosaic for that character
Two cell populations
in adult cat:
Active X
Early embryo:
X chromosomes
Cell division
and X Inactive X
chromosomeInactive X
inactivation
Allele for
orange fur
Allele for
black fur
Figure 15.11
Active X
Orange
fur
Black
fur
What are Linked Genes?
Genes located close together on the same
chromosome and tend to be inherited together
Generally do not follow Mendel’s law of
independent assortment
How Linkage Affects Inheritance: Scientific Inquiry
• Morgan did other experiments with fruit flies
– To see how linkage affects the inheritance of two
different characters
• Morgan crossed flies
– That differed in traits of two different characters
P Generation
(homozygous)
EXPERIMENT
Morgan first mated true-breeding
x
Wild type
wild-type flies with black, vestigial-winged flies to produce
Double mutant
(gray body,
heterozygous F1 dihybrids, all of which are wild-type in
(black body,
normal
wings)
appearance. He then mated wild-type F1 dihybrid females with
vestigial wings)
b+ b+ vg+ vg+
black, vestigial-winged males, producing 2,300 F2 offspring,
which he “scored” (classified according to
phenotype).
Double mutant
(black body,
vestigial wings)
b b vg vg
F1 dihybrid
Double mutant
TESTCROSS
(wild type)
(black body, x
(gray body,
vestigial wings)
normal wings)
CONCLUSION
If these two genes were on
different chromosomes, the alleles from the F1 dihybrid
would sort into gametes independently, and we would
expect to see equal numbers of the four types of offspring.
If these two genes were on the same chromosome,
we would expect each allele combination, B+ vg+ and b vg,
to stay together as gametes formed. In this case, only
offspring with parental phenotypes would be produced.
Since most offspring had a parental phenotype, Morgan
concluded that the genes for body color and wing size
are located on the same chromosome. However, 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.
Figure 15.5
Double mutant
(black body,
vestigial wings)
b b vg vg
b+ b vg+ vg
RESULTS
b vg
b+vg+
b vg
965
944
Wild type
Black(gray-normal) vestigial
b+ vg
b vg+
206
Grayvestigial
185
Blacknormal
Sperm
b+ b vg+ vg b b vg vg b+ b vg vgb b vg+ vg
Parental-type
offspring
Recombinant (nonparental-type)
offspring
In summary
• Morgan determined that
– non-linked genes should assort independently and
produce offspring with a 1:1:1:1 phenotypic ratio
– Most offspring of his cross resembled the parents
(either wild type or double mutant)
– Therefore, these traits were inherited together
because their genes were located on the same
chromosome.
– But some offspring had new combinations
Genetic Recombination
• results in offspring with combinations of traits
that differ from those found in either parent.
• Genetic recombination and linkage (what was
observed in Morgan's cross)
– Parental types – have phenotypes like one or the
other of the P generation parents
– Recombinant types (recombinants) have
combinations of the two traits that are unlike the
parents
How does crossing over affect linked
genes?
•
Linked genes do not assort independently
– Yet there were new combinations of flies that were unlike
the parental types. How did Morgan account for these
recombinants?
• Recombination of linked genes occurs due to crossing over
– Occurs during prophase I of meiosis
• A linkage map is a genetic map based on recombination
frequencies
– A genetic map is an ordered list of the genetic loci along a
particular chromosome
Abnormal Chromosome Number
• Alterations of chromosome number or
structure cause some genetic disorders
• Large-scale chromosomal alterations
– Often lead to spontaneous abortions or cause a
variety of developmental disorders
What causes abnormal chromosome
• Nondisjunction
numbers
– Pairs of homologous chromosomes do not separate
normally during meiosis
– Gametes contain two copies or no copies of a
particular chromosome
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Gametes
n+1
Figure 15.12a, b
n+1
n1
n+1
n –1
n–1
Number of chromosomes
(a) Nondisjunction of homologous
chromosomes in meiosis I
n
n
(b) Nondisjunction of sister
chromatids in meiosis II
Abnormal chromosome number
• Aneuploidy
– Is a condition in which offspring have an abnormal
number of a particular chromosome
– Trisomic-if the aneuploidy cell is 2n+1
– Monosomic – if the aneuploidy cell is 2n-1
– Polyploidy – more than 2 complete chromosome
sets (3n) or (4n)
Abnormal chromosome number
disorders
Down Syndrome (autosomal)
Also known as Trisomy 21, because there is an extra
copy of chromosome #21
Affects 1 in every 691 births
Symptoms
Mild to severe mental retardation
Birth defects
Physical problems
low muscle tone, a single crease across the palm of the
hand, a slightly flattened facial profile and an upward
slant to the eyes.
Children with Down syndrome have a higher incidence
of infection, respiratory, vision and hearing problems as
well as thyroid and other medical conditions. Approx.
40% have congenital heart defects.
Other Examples of disorders in which a person has additional autosomal
chromosomes
•
Edward’s syndrome
– Having an additional chromosome #18
• 2nd most common trisomy
• Mental retardation, defects in the hands and head, including the eyes and ears
•
Patau’s syndrome
– Having an additional chromosome #13
• Severely retarded individuals with a cleft palate and lip, an extra finger on each
hand, malformations of the eyes and ears, a small head and other abnormalities.
For both disorders the survival rate is 10% survive the first year
Disorders caused by having additional
or missing sex chromosomes
Turner Syndrome
• Disorder in Females
– Missing one X chromosome (XO)
• Women are sterile due to lack of ovarian development
• Short stature
• Webbed neck and turning out
of the elbows
– Treatments
• Growth hormones
• Estrogen replacement
Klinefelter’s Syndrome
• A Male disorder
• Having an extra X chromosome
– May be XXXY or even XXXXY
• Symptoms
– Usually normal sized or tall and thin
• Breast development, small testicles
– Few sperm, infertile
– Delayed motor function and speech
• Treatments
– testosterone
Chromosome Structure Abnormalities
honors bio
• Occur when chromosomes are missing or
have additional “parts”
• Examples:
– Cri-du-Chat syndrome (“cry of the cat”)
• Caused by a deletion of part of chromosome #5
• Technically no genetic information is lost.
• Individuals with this syndrome have an unusual cry
which sounds like a kitten’s meow.
• Other symptoms include: downward slant to eyes,
mental retardation, small head and jaw, low set or
abnormally shaped ears, low birth weight.
Chromosome Structure Abnormalities
honors bio
• Fragile X syndrome
– Appears as if the end of the X chromosome is loose or
has broken off due to many repeats of a DNA segment
– Occurs predominantly in males
• Individuals will have varying degrees of mental
retardation, are shorter than average, have large
heads with long faces and have prominent ears
• Females with one fragile X and one normal X are
considered to be carriers
• It is the most common inherited form of mental
retardation.
Alterations of Chromosome Structure
• Breakage of a chromosome can lead to four
types of changes in chromosome structure
– Deletion
– Duplication
– Inversion
– Translocation
• Alterations of chromosome structure
(a) A deletion removes a chromosomal
segment.
(b) A duplication repeats a segment.
(c) An inversion reverses a segment within
a chromosome.
(d) A translocation moves a segment from
one chromosome to another,
nonhomologous one. In a reciprocal
translocation, the most common type,
nonhomologous chromosomes exchange
fragments. Nonreciprocal translocations
also occur, in which a chromosome
transfers a fragment without receiving a
fragment in return.
Figure 15.14a–d
A B C D E
F G H
A B C D E
F G H
A B C D E
F G H
A B C D E
F G H
Deletion
Duplication
Inversion
A B C E
F G H
A B C B C D E
A D C B E
F G H
M N O C D E
Reciprocal
translocation
M N O P Q
R
A B P
Q
F G H
R
F G H
• Certain cancers
– Are caused by translocations of chromosomes
Genomic Imprinting
• The phenomenon is called imprinting because the
basic idea is that there is some imprint that is put
on the DNA in the mother's ovary or in the father's
testes which marks that DNA as being maternal or
paternal, and influences its pattern of
expression—what the gene does in the next
generation in both male and female offspring.
Imprinted genes are at high risk for envolvement in
diseases since a single genetic mutation or an
environmentally-induced genetic change can alter their
function.
• Genomic imprinting is a fascinating phenomenon, and raises an
interesting question: If information about the sex of the parent
in the previous generation can be transmitted by such
mechanisms, is there other historical information input from the
environment that can be transmitted to the current generation
and influence genetic expression? Would it be possible that if
my great-grandmother experienced a famine or lived in a time of
war, that this has put an imprint on the genome which is
influencing gene expression in my own body?
Organelle Genes
• Not all inherited DNA is from nuclear
chromosomes
• Chloroplasts and mitochondria have their own
DNA
• Some disorders are caused by inheritance of
extranuclear genes, those genes contained for
example in mitochondria.
– Some may contribute to diabetes, heart disease and
Alzheimer’s disease