Transcript ap15-ChromosomalBasisofInheritance 07-2008

Homework for Wednesday, Jan 30
• P. 285: problems 4 and 7
• In Student Study Guide:
– Interactive questions: 15.2, 15.3, 15.4
– Test your Knowledge:2, 6, 7, 20
You get 5 minutes to prepare for the class
answers to one of the following.Teams of
2-3:
• 1.What is the Chromosome theory of inheritance?
• 2. Distinguish between “wild-type”; “mutant” phenotypes, and
give an example
• 3. Where are the red/white eye alleles located in fruit flies?
What did Morgan discover?…….
• 4. explain Fig. 15.3
• 5. Distinguish between sex-linked genes and linked genes.
• 6. What is Genetic recombination?
• 7. Refer to Fig. 15.4-give the phenotype of the wild-type
female, and the double mutant male (draw on board)
CHAPTER 15
THE CHROMOSOMAL
BASIS
OF
INHERITANCE
Section A: Relating Mendelism to Chromosomes
1. Mendelian inheritance has its physical basis in the behavior of
chromosomes during sexual life cycles
2. Morgan traced a gene to a specific chromosome
3. Linked genes tend to be inherited together because they are
located on the same chromosome
4. Independent assortment of chromosomes and crossing over
produce genetic recombinants
5. Geneticists use recombination data to map a chromosome’s
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genetic loci
The Chromosomal Theory
of Inheritance
• Genes have
specific loci on
chromosomes
and it is the
chromosomes that
undergo
segregation and
independent
assortment
2. Morgan traced a gene to
a specific chromosome
• Thomas Hunt Morgan was the
first to associate a specific
gene with a specific
chromosome
• early 20th century.
• Drosophila melanogaster, a fruit fly species
that eats fungi on fruit.
– prolific breeders
– generation time of two weeks.
– Fruit flies have three pairs of autosomes and a
pair of sex chromosomes (XX in females, XY in
– Morgan discovered a single male fly with
white eyes instead of the usual red.
• wild type: the normal or most
frequently observed phenotype
• mutant phenotypes: Alternatives
Fig. 15.2
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• White Eyed Male x Red-eyed female
offspring
•
F1 offspring X F1
the F2 offspring.
all red eyed
classic 3:1 phenotypic ratio in
• Surprisingly, the white-eyed trait
appeared only in males.
– All the females and half the males had red eyes.
• Morgan concluded that a fly’s eye
color was linked to its sex.
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• Morgan deduced that
– eye color is linked to
sex AND
– the gene for eye color
is only located on
the X chromosome.
– Sex-Linked Genes
Fig. 15.3
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Linked Genes
• linked genes: Genes located on the
same chromosome.
• They tend to be inherited together
because the chromosome is passed
along as a unit.
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Figure 15.4 Evidence for linked genes in Drosophila
Figure 15.5a Recombination due to crossing over
Genetic Recombination
• Production of offspring with new
combos of traits different from
those combos found in the parents
• Parental types
• Recombinants
• Recombinant frequency
(# recombinants/total offspring)100
• 1 map unit = 1% recombinant frequency
Genetic recombination:
• Can result from:
• 1. Independent assortment of
chromosomes (the recombination of
unlinked genes).
2. crossing over ( the recombination of
linked genes)
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Figure 15.5b Recombination due to crossing over
Recombinant Frequency
Problem
• A wild type fruit fly (heterozygous
for gray body color and red eyes)
• was mated with a black fruit fly
with purple eyes.
• What is the recombinant frequency
for these genes?
• Wild type – 721
• Black purple – 751
• Gray purple – 49
• Black red - 45
Recombinant Frequency
Problem - Answer
• Total offspring - 1566
• Parental types – 1472
• Recombinants – 94
• Frequency = 94/1566 *100
= 6.0%
Recap-Morgan’s test-cross
(2 traits)
• Most of the F2 offspring looked like
the parents( because the genes were
linked-same chromosome)
• Explaining why the were greater
number of recombinant phenotypes
(resulted from some other force of
nature-----crossing over)
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– Under independent assortment (genes
not linked) the testcross should
produce a 1:1:1:1 phenotypic ratio.
– If completely linked, we should expect to
see a 1:1:0:0 ratio with only parental
phenotypes among offspring.
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5. Mapping chromosomes
• Alfred Sturtevant
• Linkage map: a
genetic map (GENES
& THEIR RELATIVE
LOCTIONS) based
upon recombination
frequencies.
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• The farther apart two genes are,
the higher the probability that a
crossover will occur between
them & therefore a higher
recombination frequency.
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• A linkage map provides an imperfect
picture of a chromosome.
– Map units indicate relative distance
and order, not precise locations of
genes.
• Cytological maps.
– These indicated the positions of genes with
respect to chromosomal features.-like banding
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three fruit fly genes, body color (b), wing size
(vg), and eye color (cn).
– The recombination frequency between cn and b is 9%.
– The recombination frequency between cn and vg is
9.5%.
– The recombination frequency between b and vg is 17%
Fig. 15.6
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• Map units: the distance between
genes
• 1 map unit =1% recombination
frequency
• Centimorgan
• relative distance and order, not
precise locations of genes.
–.
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Practice: Interactive Question
15.2 from student work book
• Recombination frequencies for gene
pairs. Create linkage map, show
map units between gene loci.
• J,k 12%
• J,m 9%
• K,l 6%
• l,m 15%
answer
K
L
6
J
6
M
9
• Some genes on a chromosome are so
far apart that a crossover between
them is virtually certain.
• Frequency of recombination
reaches has a maximum value of
50%
• Same as recom. Freq. as if found on
separate chromosomes, and are
inherited independently.
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Homework for Wednesday, Jan 30
• P. 285: problems 4 and 7
• In Student Study Guide:
– Interactive questions: 15.2, 15.3, 15.4
– Test your Knowledge:2, 6, 7, 20
CHAPTER 15
THE CHROMOSOMAL BASIS OF
INHERITANCE
Section B: Sex Chromosomes
1. The chromosomal basis of sex varies with the organism
2. Sex-linked genes have unique patterns of inheritance
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The chromosomal basis of sex
varies with the organism
1. In the X-Y system, X and Y rarely
undergo crossing over.
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• 2. X-0 system
– some insects:
– XX=female; XO-male
• Z-W system
– Birds:
– females determine sex
ZZ-male; ZW-females
• the haplo-diploid system:
– Bees, ants: no sex chromosomesFemales develop from fertilized
eggs (2n);
Males from unfert. eggs
(haploid)
Fig. 15.8
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• In humans, the anatomical signs of
sex first appear when the embryo is
about two months old.
• In individuals with the SRY gene (sexdetermining region of the Y
chromosome), the generic embryonic
gonads are modified into testes.
– Activity of the SRY gene triggers a cascade of
biochemical, physiological, and anatomical
features because it regulates many other
genes.
– In addition, other genes on the Y chromosome
are necessary for the production of functional
sperm.
• In individuals lacking the SRY gene, the generic
embryonic gonads develop into ovaries.
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The Chromosomal Basis of Sex in
Humans
• Males-heterogametic (XY)
• Females homogametic ( XX)
• Whether an embryo develops into
male of female depends upon the Y
chromosome.
• SRY gene
– Triggers cascade of events—normal
testicular development
– SRY absent-gonads develop into ovaries
2. Sex-linked genes have unique
patterns of inheritance
Fig. 15.9
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Sex-linked traits
• Males are hemizygous
–More males than females
have sex-linked disorders
• Sex-linked disorders
• 1. Duchenne muscular dystrophy
affects one in 3,500 males born in
the United States.
– rarely live past their early 20s.
– This disorder is due to the absence of an
X-linked gene for a key muscle protein,
called dystrophin.
– progressive weakening of the muscles
and a loss of coordination.
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• 2.Hemophilia sex-linked, recessive
absence of one or more clotting
factors that normally slow and then
stop bleeding.
• prolonged bleeding
– Bleeding in muscles and joints can be
painful and lead to serious damage.
– treated with intravenous injections of the
missing protein.
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Sex Linkage Problem
Hemophilia is caused by a sex-linked
recessive allele.
A man with hemophilia marries a woman
with normal clotting factors.
What is the probability that they will have
a daughter with hemophilia?
What is the probability that they will have
a son with hemophilia?
What is the probability that their son will
have hemophilia?
X-Inactivation in Females
Compensating for the missing X.
Lyon Hypothesis:
In female mammals, only one X is
fully functional
• Barr body
–Inactive X chromosome (random)
–condenses
–Reactivated in gonadal cells at
meiosis
• Mosaic of inactive maternal and
paternal X chromosomes (calico
cats)
• In humans, this mosaic pattern is
evident in women who are
heterozygous for a X-linked mutation
that prevents the development of
sweat glands.
– A heterozygous woman will have patches
of normal skin and skin patches lacking
sweat glands.
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• Similarly, the orange and black
pattern on tortoiseshell cats is due
to patches of cells expressing an
orange allele while others have a
nonorange allele.
Fig. 15.10
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Figure 15.10x Calico cat
X-inactivation Produces
Tortoiseshell Cats
• X-linked system with two alleles
– heterozygous females express both alleles in a
mosaic pattern, depending on active gene
CHROMOSOMAL BASIS OF
INHERITANCE:
ERRORS AND EXCEPTIONS
Nondisjunction and Abnormal
Chromosome Numbers
• aneuploidy (an abnormal
chromosome number)
– normal gamete fuses with a gamete
from a nondisjunction (effect usually
severe)
– trisomic 2n + 1 total chromosomes
– monosomic 2n - 1 chromosomes.
• Nondisjunction spindle incorrectly
separates chromosome during
karyokinesis
• usually lethal
Polypoidy
• organisms with more than two
complete sets of chromosomes
(effect often less severe)
• usually occurs when a normal gamete
fertilizes another gamete in which there
has been nondisjunction of all its
chromosomes
– produces a triploid (3n) zygote (2n + 1n)
Polyploid is Common in Plants,
but Rare in Animals
• polyploidy plays an important role in
the evolution of plants
– economically important
– at least one species of
rodent may be a product of polyploidy
• Polyploids are more nearly
• normal in phenotype than
Abnormal Chromosome
Numbers and Human
Disorders
• most aneuploid zygotes are non-viable,
and spontaneously abort early in
development
– developmental problems result from an
imbalance among gene products
• certain aneuploid conditions upset the
balance less, survive to term and
beyond
– individuals have a set of symptoms - a
syndrome - characteristic of the type of
Down Syndrome
• trisomy 21, three copies of
chromosome 21
– affects one in 700 children born in U.S.
• severely alters an individual’s
phenotype in specific ways.
Incidence of Trisomy Increases
with Age in Women
• usually result from nondisjunction
during gamete production in one
parent
• frequency of Down syndrome
correlates with age of mother
– may be linked to some age-dependent
abnormality in spindle checkpoint during
meiosis I, leading to nondisjunction
• incidence of other trisomies also
increase with maternal age, but are
usually lethal if autosomal
Nondisjunction of Sex
Chromosomes
• produces a variety of viable aneuploid
conditions in humans
• unlike autosomes, aneuploidy in
sex chromosomes upsets genetic
balance less severely.
– may be because Y chromosome
contains relatively few genes
– extra copies of X chromosome become
inactivated as Barr bodies in somatic
cells
XX or XY Nondisjuntions
• XXY males Klinefelter’s syndrome,
(1/2000)
– sterile individuals with male sex organs
– may be feminized. They are of normal
intelligence
• XYY males often taller than average
• XXX females Trisomy X (1/2000)
– produces healthy females
• XO females Turner’s syndrome (1/5000)
– produces phenotypic, but immature females
Structural Changes in Chromosomes
Breakage of a chromosome can lead to
four types of changes in chromosome
structure.
• 1. A deletion occurs when a
chromosome fragment lacking a
centromere is lost during cell division.
-Usually lethal
• 2. A duplication occurs when a
fragment becomes attached as an
extra segment to a sister chromatid.
Fig. 15.13a & b
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• 3. An inversion occurs when a
chromosomal fragment reattaches to
the original chromosome but in the
reverse orientation.
• 4. In translocation, a chromosomal
fragment joins a nonhomologous
chromosome.
– Some translocations are reciprocal,
others are not.
Fig. 15.13c & d
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• Deletions and duplications are common
in meiosis.
– Homologous chromatids may break and
rejoin at incorrect places, such that one
chromatid will lose more genes than it
receives.
•.
– Duplications and translocations are
typically harmful.
• Reciprocal translocation or inversion
can alter phenotype because a gene’s
expression is influenced by its location.
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Structural Changes and
Human Disorders
• cri du chat syndrome caused by a
specific deletion in chromosome 5
– mentally handicapped, small head,
unusual facial features, cry sounds like
the meowing of a distressed cat.
– fatal in infancy or early childhood
• chronic myelogenous leukemia
(CML)
– CML translocation between tips of
chromosome 22 and chromosome 9
2. Phenotypic imprinting
• effects of some mammalian genes
depends on whether they were
inherited from mother or father
• alleles for most genes have same
expression regardless of source
(maternal or paternal)
• expression of some traits in
mammals, vary depending on origin
of inherited alleles.
– genes involved are not linked to sex
and may or may not lie on the X
Prader-Willi and Angelman
Syndromes
• both due to a deletion of a specific
segment of chromosome 15
• different phenotypic effects are due to
genomic imprinting
– Prader-Willi syndrome, mental
retardation, obesity, short stature, and
unusually small hands and feet
• abnormal chromosome from their father.
– Angelman syndrome, spontaneous
laughter, jerky movements, and other
motor and mental symptoms
Fragile X Syndrome
• leads to various degrees of mental
retardation, appears to be subject to
genomic imprinting.
– abnormal X chromosome in which tip
hangs on by a thin thread of DNA.
– disorder affects 1/1,500 males and
1/2,500 females
• inheritance of fragile X is complex
• syndrome is more common when
abnormal chromosome is inherited
from mother
Genomic Imprinting
• a gene on one homologous
chromosome is silenced, other is
expressed
• imprinting status of a given gene
depends on whether gene resides in
a female or a male
– effects of alleles on offspring, depend on
whether they arrive in zygote via ovum
or via sperm
• silencing mechanism depends on
presence or absence of methylation,
not well understood
Genomic
Imprinting is
Reset Each
Generation
• each new generation, all
imprints are “erased” in
gamete-producing cells.
• chromosomes are all
“reimprinted” according
to individuals sex
• Certain aneuploid conditions upset
the balance less, leading to survival
to birth and beyond.
– These individDevelopmental problems
result from an imbalance among
gene products.
– These individuals have a set of
symptoms - a syndrome characteristic of the type of
aneuploidy.
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• Chromosomal translocations
• Some individuals with Down
syndrome have the normal number
of chromosomes but have all or
part of a third chromosome 21
attached to another chromosome
by translocation.
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2. The phenotypic effects of
some mammalian genes depend
on whether they were inherited
from the mother or the father
(imprinting)
• For most genes it is a reasonable assumption
that a specific allele will have the same effect
regardless of whether it was inherited from
the mother or father.
• However, for some traits in mammals, it does
depend on which parent passed along the
alleles for those traits.
– The genes involved are not sex linked and may or
may not lie on the X chromosome.
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• Two disorders with different
phenotypic effects, Prader-Willi
syndrome and Angelman syndrome,
are due to the same cause, a deletion
of a specific segment of chromosome
15.
– Prader-Willi syndrome is characterized by
mental retardation, obesity, short stature,
and unusually small hands and feet.
– These individuals inherit the abnormal
chromosome from their father.
– Individuals with Angelman syndrome
exhibit spontaneous laughter, jerky
Copyrightmovements,
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as Benjamin
Cummingsmotor and mental
and
other
• The difference between the disorders
is due to genomic imprinting.
• In this process, a gene on one
homologous chromosome is silenced,
while its allele on the homologous
chromosome is expressed.
• The imprinting status of a given gene
depends on whether the gene resides
in a female or a male.
– The same alleles may have different
effects on offspring, depending on
whether they arrive in the zygote via the
ovum or via the sperm.
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• In the new
generation, both
maternal and
paternal imprints are
apparently “erased”
in gamete-producing
cells.
• Then, all
chromosomes are
reimprinted according
to the sex of the
individual in which
they reside.
Fig. 15.15
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• Fragile X syndrome, which leads to
various degrees of mental retardation,
also appears to be subject to genomic
imprinting.
– This disorder is named for an abnormal X
chromosome in which the tip hangs on by
a thin thread of DNA.
– This disorder affects one in every 1,500
males and one in every 2,500 females.
• Inheritance of fragile X is complex, but the syndrome is more
common when the abnormal chromosome is inherited from
the mother.
– This is consistent with the higher
frequency in
– Imprinting by the mother somehow causes it.
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males.
3. Extranuclear genes exhibit a nonMendelian pattern of inheritance
• Not all of a eukaryote cell’s genes are
located in the nucleus.
• Extranuclear genes are found on small
circles of DNA in mitochondria and
chloroplasts.
• These organelles reproduce
themselves.
• Their cytoplasmic genes do not display
Mendelian inheritance.
– They are not distributed to offspring
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• Karl Correns first observed
cytoplasmic genes in plants in 1909.
• He determined that the coloration of
the offspring was determined only by
the maternal parent.
• These coloration patterns are due to
genes in the plastids which are
inherited only via the ovum, not the
pollen.
Fig. 15.16
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• Because a zygote inherits all its
mitochondria only from the ovum,
all mitochondrial genes in
mammals demonstrate maternal
inheritance.
• Several rare human disorders are
produced by mutations to
mitochondrial DNA.
– These primarily impact ATP supply by
producing defects in the electron
transport chain or ATP synthase.
– Tissues that require high energy supplies
(for example, the nervous system and
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