Download Document

Genetics
Ch. 10 & 15
Mrs. Daniels
Advanced Biology
rev. January 2007
What do you know already?
• Brainstorm on a sheet of paper:
• Do a type I writing at least 15 lines long
• (skip a line in between)
• Write as much as you remember about
genetics from general biology or from your
personal experience.
Sexual Reproduction
• We know already that in animals and many
other organisms sexual reproduction is the
means by which offspring are produced
• The joining of the male and female gametes
results in a diploid cell which develops into
the offspring
• So how alike are you to your parents?
• Assignment: bring a picture of one or both
of your parents with you tomorrow
Heredity Theories
• Blending Theory:
• Based on their observations from
ornamental plant breeding, 19th century
biologists realized that both parents
contribute to the characteristics of the
offspring
• They proposed that the hereditary material
of both parents mixes in the offspring like a
liquid and then cannot be separated
• According to the blending theory:
• Individuals of a population should reach a
uniform appearance after many generations
• Once hereditary traits are blended, they can no
longer be separated out to appear again in later
generations
• The theory was inconsistent however with the
following observations:
• Individuals in a population did not reach a
uniform appearance
• Some inheritable traits skip one generation only
to reappear in the next
• Particulate theory of heredity:
• Gregor Mendel began to discover the
fundamentals of heredity in the 1860’s and
replaced the blending theory with this
theory
• Parents transmit to their offspring discrete
inheritable factors (now called genes) that
remain as separate factors from one
generation to the next
• How did he figure this out?
Mendel’s Difference
• Mendel used key elements of the scientific
method in his study of heredity
• But unlike most nineteenth century
biologists, he used a quantitative approach
(due to Doppler’s influence)
How did Mendel conduct his
experiments?
• In 1857, he was living in an Augustinian
monastery where he bred garden peas
• He kept strict control over mating to ensure
the parentage of new seeds
• Petals of the pea flower enclose pistil and
stamens which prevent cross-pollination
• Immature stamens can be removed to
prevent self-pollination
• He used an artist’s brush to transfer pollen
• He chose seven characteristics called
characters which occurred in two alternative
forms (traits):
• 1. Flower color (purple or white)
• 2. Flower position (axial or terminal)
• 3. Seed color (yellow or green)
• 4. Seed shape (round or wrinkled)
• 5. Pod shape (inflated or constricted)
• 6. Pod color (green or yellow)
• 7. Stem length (tall or dwarf)
Seven characters in Mendel’s study of pea plants
• Mendel began his experiments with truebreeding plants (which always produce offspring
with the same traits as the parents when the
parents self-fertilize)
• The true breeding plants of such a cross
pollination are called the P generation (parental)
• The hybrid offspring of the P generation are the
F1 generation (first filial)
• Allowing the F1 generation to self-pollinate
produces the next generation called the second
filial (F2)
His Conclusions
• After observing the transmission of traits
for at least 3 generation, he arrived at two
principles of heredity
• Law of segregation
• &
• Law of independent assortment
• Mendel’s principles of inheritance
– Segregation
• During meiosis, alleles for each locus segregate
– Independent assortment
• Alleles of different loci distributed randomly
into the gamete
• Results in recombination
• Production of new gene combinations not
found in parent
Law of Segregation
• When Mendel crossed true-breeding plants with
different character traits, he found that the traits did
not blend
• A cross between true-breeding varieties: one with
purple flowers and one with white flowers resulted
in 100% purple-flowered in the F1 offspring and
75% purple and 25% white-flowered F2 offspring
• Conclusion: the inheritable factor for the white
flowers was not lost, therefore (factors) genes can be
separated
• Note: experiment was repeated with the other 6 characteristics & same
3:1 ratio was found
• From Mendel’s observations, he came up
with four hypotheses and tested them. His
conclusions resulted in his “2nd law”
• Mendel’s Law of Segregation:
• Allele pairs (alternative forms for a gene)
separate (segregate) during gamete
formation and the paired condition is
restored by the random fusion of gametes at
fertilization
• The combinations resulting from these
genetic crosses may be predicted by using a
Punnett Square
Punnett Squares
• Rules:
• Place each allele in the female parent across the
top of the squares
• Place each allele in the male parent along the
side on each square
• Carry the allele across into each of the squares in
its row/column
• The new combinations are the predictions for the
offspring (ratios)
TestCross
• Because some alleles are dominant over others, the
genotype of an organism may not be apparent
• Ex. A pea plant with purple flowers could be either
PP or Pp
• To determine which genotype the plant has, it can
be crossed with a known genotype which is the
homozygous recessive
• The homozygous recessive genotype is the only
one that is known by its phenotype because the
recessive allele is being displayed (in order for that
to happen it must have two copies of it)
TestCross cont.
• If the dominant phenotype is crossed with the
homozygous recessive and results in offspring all
having the dominant phenotype, the offspring are
heterozygous
• This means that the unknown genotype of the parent
is homozygous dominant
• If the cross results in half dominant and half
recessive phenotypes, the offspring are half
heterozygous and half homozygous recessive
• This means the parent must have been heterozygous
Monohybrid and Dihybrid
• Monohybrid cross: breeding experiment using
parental varieties of a single characteristic
• From these experiments, Mendel deduced the
Law of Segregation
• Dihybrid crosses: breeding experiment using
parental varieties differing in two characteristics
(actually: two heterozygous)
• From these experiments, Mendel deduced his
Law of Independent Assortment
Law of Independent Assortment
• His law of independent assortment states that
each allele pair segregates independently of
other gene pairs during gamete formation
• Both this law and his law of segregation are
founded on the fact that the events sorting and
separating of alleles during gamete formation as
well as fusion of gametes during fertilization is
totally random
Probability
• By using laws of probability, we can predict the
most likely genotypes of the offspring (if we
know the parental genotypes)
• The probabilities of all possible outcomes for an
event must add up to 1
• An event that is certain to occur has a probability
value of 1 and if it is certain to not occur, it has a
probability value of 0
• Likelyhood for an event to occur falls on the
probability scale between 0 and 1
Probability
•
•
•
•
•
•
•
•
Ex. When tossing a two-headed coin:
Tossing heads = prob. of 1
Tossing tails = prob. of 0
Total of 1 + 0 = 1
Ex. When tossing a normal coin:
Tossing heads = 1/2
Tossing tails = 1/2
Total of 1/2 + 1/2 = 1
Rules
of probability
Rules of Probability
• Rule of multiplication: the probability that
independent events will occur simultaneously is the
product of their individual probabilites
• Ex. In a monohybrid cross between pea plants that are
heterozygous for color (Pp), what is the probability that
the offspring will be homozygous recessive?
• Prob. that an egg from F1 will receive a p allele = 1/2
• Prob. that a sperm from F1 will receive a p allele= 1/2
• The overall probability that two recessive alleles will
unite at fertilization: 1/2 x 1/2 = 1/4
Rules of Probability
• Rule of addition: the probability of an even that can
occur in two or more independent ways is the sum
of the separate probabilities of the different ways.
• Ex. When crossing two pea plants that are Pp, what
is the probability that the offspring will be
heterozygous?
• There are two ways in which a heterozygote may be
produced: the P may be in the egg and the p in the
sperm OR the p may be in the egg and the P in the
sperm.
Rules of Probability
• The probability that the offspring will be
heterozygous is the sum of the probabilities of those
two possible ways:
• Prob that the dominant allele will be in the egg with
the recessive allele in the sperm = 1/2 x 1/2 = 1/4
• Prob that the dominant allele will be in the sperm
with the recessive allele in the egg = 1/2 x 1/2 = 1/4
• Prob that the offspring will be heterozygous:
• 1/4 + 1/4 = 1/2
Try to solve
• In a trihybrid cross (both parents have the
genotype AaBbCc), what is the probability
that they will produce an offspring with
aabbcc?
• Clue: treat it as three separate monohybrid
crosses which occur independently but
simultaneously (so use the rule of mult.)
Answer:
• Aa x Aa: prob for aa offspring = 1/4
• Bb x Bb: prob for bb offspring = 1/4
• Cc x Cc: prob for cc offspring = 1/4
• Prob of them all occurring simultaneously:
• 1/4 x 1/4 x 1/4 = 1/64
Incomplete dominance
• There are cases when one allele is not
completely dominant over the other so the
heterozygote expresses an intermediate or
blending of the two phenotypes
• For example, red snapdragons (RR) and white
snapdragons (rr) are crossed.
• The heterozygous offspring display only part of
the dominant red phenotype, blended with a bit
of white to make pink.
The range of dominance
• The alleles can range from completely
dominant over the other (recessive) allele to
incomplete dominance and finally to
codominance (no dominance)
• You are now familiar with the complete
dominance and the incomplete dominance
The range of dominance
• Codominance is where both alleles are
equally expressed in phenotype
• Instead of a blending of the two phenotypes,
both phenotypes can be seen individually
• Ex. ML markers on the outside of cells
• Can display only the M marker LMLM
• Can display only the N marker LNLN
• Or both can be displayed LMLN
Multiple Alleles
• There can be multiple alleles active at the same
locus
• Ex. ABO blood types have 3 alleles at that gene
locus
• IA, IB, i
• IA codes for the A antigen, IB codes for the B
antigen, i codes for neither A nor B
• A & B are codominant (both are expressed), but
both are dominant over i
• Every person only carries 2 of the 3 alleles
Multiple alleles in rabbits
Pleiotropy
• The ability of a single gene to have multiple
phenotype
• Ex. Sickle-cell anemia is caused by a single gene
defect, but has multiple symptoms
• Ex. One gene can influence a combination of
unrelated characteristics
• An abnormal gene in tigers and Siamese cats can
cause both abnormal pigmentation and a crosseyed condition
Epistasis
• Interaction between 2 non-allelic genes
where one modifies the expression of the
other
• Causes a deviation from 9:3:3:1 ratio
Epistasis in Labrador retrievers
Polygenic Inheritance
• Many characteristics are not an “either/or”
classification. Many are quantitative characters
that vary in a continuum within a population
• Vary by degree rather than by discrete differences
• Usually determined by many segregating loci or
“polygenic inheritance” (two or more genes
determine a single phenotypic character with an
additive effect)
Polygenic Inheritance
• Ex. Skin pigmentation in humans appears to be
controlled by at least 3 separately inherited genes
• Simplified version: A,B, and C are three genes that
contribute one “unit” of darkness to the phenotype.
• These are each incompletely dominant over a,b,& c
• A person with AABBCC would be very dark and a
person with aabbcc would be very light
• A person with AaBbCc would have an intermediate
shade of skin color
• Environmental factors such as sun exposure could
also alter the phenotypic expression
Polygenic
inheritance in
human skin
pigmentation
Environmental Impact
• The environmentally-induced phenotypic
range of a given gene is called the norm of
reaction for a genotype
• Altitude, activity level, sun exposure, diet,
and many more are all examples of factors
that could alter the expression of a gene
Pedigrees
• Our understanding of Mendelian inheritance
is based on the analysis of family pedigrees
or results of matings that have already
occurred.
• Pedigree: a family tree that diagrams
relationships among parents and offspring
across generations and shows the
inheritance pattern of a particular
phenotypic character
Pedigrees
• A horizontal line indicated a mating
• Offspring are listed from left to right in birth
order
• Males are square and females are circles
• Shaded symbols indicate individuals showing the
trait
• Pedigrees can be useful in determining if a trait is
dominant or recessive; also can be used to predict
the occurrence of a trait in future generations
I
1
2
Figure 15-2
Page 293
3
4
II
1
2
3
4
5
Key:
Normal female
Normal male
III
Mating
Albino female
Albino male
Siblings
produced
by a
mating
Recessively Inherited Disorders
• Recessive alleles that cause human
disorders are usually defective versions of
the normal allele (malfunctioning protein or
no protein at all)
• Three examples: cystic fibrosis, Tay-Sachs
disease, and sickle-cell disease
Recessively Inherited Disorders
• Cystic Fibrosis:
– strikes 1 in 2,500 caucasians (rarer in other races)
– Defective chloride channels across cell membrane
– Symptoms result from the accumulation of thickened mucus
in the pancreas and lungs
• Tay-Sachs Disease:
– Occurs in 1 out of 3,600 births (100 times higher among
central European Jews than Mediterranean Jews and nonJews)
– Brain cells of babies are unable to metabolize gangliosides
– These lipids accumulate in the brain and baby suffers
seizures, blindness, degeneration of motor and mental
performance. Usually only live a few years.
Recessively Inherited Disorders
• Sickle-cell disease:
– Most common inherited disease among African
Americans (1 in 400 in US)
– Single amino acid substitution in hemoglobin
– Abnormal hemoglobin molecules link together and
crystallize causing red blood cells to deform to a sickleshape
– The sickled-cells clog tiny blood vessels, causing the
pain and fever characteristic of the disease
– Low blood oxygen levels
– Codominant alleles
– Heterozygotes show enhanced resistance to malaria
Shared Ancestry
• Consanguinity: a genetic relationship that
results from shared ancestry
• Increases chance of homozygotes of
harmful recessives
• Stillbirths and birth defects are more
common when parents are closely related
Dominantly Inherited Disorders
• Some human disorders are dominantly inherited
• Ex. Achondroplasia (a type of dwarfism)
• Homozygous dominant (miscarriage of fetus),
homozygous recessive (normal phenotype)
• Much rarer than lethal recessives because they
cannot be masked in heterozygotes and the
developing embryo may never be born and thus
never reproduce
• Late-acting lethal dominants can escape early
elimination because they do not appear until
advanced age (ex. Huntington’s disease)
Multifactorial disorders
• More commonly, people are afflicted by
multifactorial disorders which have both
genetic and environmental influences
• Ex. Heart disease, diabetes, cancer,
alcoholism, and some forms of mental
illness
• Hereditary component is often polygenic
Technology and Fetal Screening
• Discussion
1 About 20 mL of amniotic
fluid containing cells
sloughed off from
fetus is removed
through mother's
abdomen.
Figure 15-11
Page 306
2 Fluid is
centrifuged.
3 Amniotic
fluid is
analyzed.
6 Karyotype is
analyzed for sex
chromosomes
or any chromosome
abnormality.
4 Fetal cells are
checked to
determine sex, and
Some
5 cells are grown for purified DNA is
analyzed.
2 weeks in culture
medium.
Cells are analyzed
7 biochemically for
presence of about
40 metabolic disorders.
Transabdominal
sampling
technique
Figure 15-12
Page 307
Withdrawn
chorionic villi cells
Ultrasound
probe
Catheter
Cervical
sampling
technique
Syringe
Withdrawn chorionic
villi cells
or
Chorionic
villi
Catheter
Cells are cultured; biochemical tests
and karyotyping are performed
Chromosome Theory
• Biologists observed the same ratios and
patterns that Mendel did and took it one
step further.
• Based on their observations, they predicted
that Mendelian “factors” which we now call
genes are located on chromosomes and
• It is the chromosomes that segregate and
independently assort
Thomas Hunt Morgan
• An embryologist
• Found that specific genes are found on specific
chromosomes each time they are seen
• Used D. melanogaster for his studies
• Discovered sex-linked genes (white eyed males)
• Called the most common character type in a
natural group the “wild type” and deduced that all
others originated as mutations (mutants)
Why use Drosphila?
•
•
•
•
•
They:
Are easily cultured in the lab
Are prolific breeders
Have a short generation time
Have only 4 pairs of chromosomes (easily
seen with a microscope)
• Can you think of more?
Linked genes
• Each chromosome has hundreds or
thousands of genes located on it
• Genes on the same chromosome tend to be
inherited together because they are near
each other on that same chromosome
• Linked genes: passed along as one unit
• Linkage
– Tendency for a group of genes on same chromosome to be
inherited together
• Recombination of linked genes
– Results from crossing-over in meiotic prophase I
– By measuring frequency of recombination, can construct
linkage map of chromosome
Genetic Recombination
• Resulting from meiosis and random
fertilization, new combinations of traits
(different than those found in the parents) can
be seen in offspring
• Parental types: progeny (offspring) that have
the same phenotype as one or both of the
parents
• Recombinants: progeny whose phenotypes
differ from either parent
Genetic Recombination
• Recombination frequency can be easily calculated
by
• (# recombinants / # total offspring) x 100 = % recombinants
• By determining the recombination frequency,
scientists were able to deduce that some genes are
not “completely linked” but are incompletely
linked
• If the genes are incompletely linked, crossing over
is able to occasionally occur between them
Mapping genetic loci
• Biologists can use recombination
frequencies to map the sequence of linked
genes on a chromosome
• Sturtevant (one of Morgan’s students) found
that the probability of crossing over
between two genes is directly proportional
to the distance between them.
• He defined one % recombination frequency
as one “map unit” on a chromosome
Mapping genetic loci
• These units are now called centimorgans
• If the recomb. frequency is 9.0%, then the
approximate distance between the two genes is
9 centimorgans
• Try placing these genes in the appropriate
order:
• b & vg have a r.f. of 17%
• cn & b have a r.f. of 9.0%
• cn & vg have a r.f. of 9.5%
Mapping genetic loci
•
•
•
•
What order are they in?
Which two are the furthest apart?
Place these on either end.
Does it make sense for the third gene to be
placed in the middle? Where in the middle?
• Do the distances (centimorgans) add up?
• Why or why not?
Mapping genetic loci
• There are actually 18.5 centimorgans between
b and vg.
• This is higher than that predicted by the r.f.
because the distance between the two genes is
great enough that double cross overs occur and
cancel out, thus lowering the r.f.
• Double cross overs are when they cross over
and then get switched back when crossing over
occurs again
Cytological Maps
• Don’t usually match up with the predicted “distance” between
genes
• A centimorgan or map unit is not an actual unit of distance as in
nanometers
• The frequency of crossing over is not the same for all
chromosomal regions
• For example, it may be more common for crossing over to happen
at the very tip of a chromosome than it would more toward the
centromere
Chromosomal Sex-determination
• Humans are able to produce their gametes by
meiosis and will pass on that genetic information
to their offspring
• Depending on the sex of the human, they may
produce only one type of gamete (X) or they may
produce two types of gametes (X) & (Y)
• Producing one type of gamete is referred to as the
homogametic sex and producing more than one is
the heterogametic sex
Sex-linked Traits (review)
• Sex-linked traits in humans usually refers to xlinked traits
• Most genes found on the Y chromosome have no
X counterpart and many times encode for traits
found only in males (ex. Testis-determining
factor)
• Fathers cannot pass sex-linked traits to their sons
(only daughters)
• Mothers pass one X on to every son and daughter
(it depends on which X has the trait)
• Far more males are found to have sex-linked
disorders
• Why?
• They only have one X
• If the disorder is caused by a homozygous
recessive situation, they only need one recessive
gene in order to have the disorder
• They are said to be hemizygous: only one copy
of a gene is present in a diploid organism
• Ex. of sex-linked disorders: color-blindness,
Duchenne muscular dystrophy, and hemophila
X-linked red-green colorblindness
X-Inactivation
• Female mammals typically will have all but one X
become inactivated
• The inactive X will condense into an object called
a Barr body, which lies dormant along the edge of
the nuclear envelope
• The Barr body becomes reactivated in gonadal
cells that undergo meiosis
• Totally random which X will become inactive
• If the female is heterozygous, about half her cells
will express one allele and the other cells will
express an alternate allele
Dosage compensation in female mammals
How does X-inactivation occur?
• Methyl groups attach to cytosine in the DNA
• Which one gets methylated?
• Barr bodies are found to have an XIST gene
(X-inactive specific transcript); an RNA that
interacts with the X chromosome and
maintains its inactivation
• There is much still unknown about the process
Variations from the Diploid #
• Nondisjunction: meiotic or mitotic error during
which certain homologous chromosomes or sister
chromatids fail to separate
• Meiotic nondisjunction: may occur in meiosis I
or II
• Results in one gamete receiving two of the same
type of chromosome and another gamete
receiving no copy. (the remaining chromosomes
may be distributed normally.)
Figure 15-4a
Page 298
XY
Nondisjunction in
first meiotic division
XY
X
Y
Figure 15-4b
Page 298
Nondisjunction
of X in second
meiotic division
Nondisjunction
of Y in second
meiotic division
Normal first
meiotic division
XX
X
Y
X
X
Y
Y
YY
Variations from the Diploid #
• Mitotic nondisjunction: also results in abnormal
number of certain chromosomes
• If it occurs in an embryonic cell, it passes the
abnormal chromosome number to a large number
of cells and can have a large consequence
Variations from the Diploid #
• Aneuploidy: condition of having an abnormal # of
certain chromosome(s)
– If a cell has a chromosome in triplicate, it is trisomic
– If a cell has a missing chromosome, it is monosomic
– Aneuploidy can cause characteristic symptoms in
survivors. Ex. Down’s syndrome (trisomy 21)
• Polyploidy: more than two complete chromosome
sets
• Triploidy (3N) or tetraploidy (4N)
• Polyploidy is common in plants
Alterations of chromosome structure
• Chromosome breakage can alter chromosome
structure in 4 ways:
• 1. Deletion: loses a fragment lacking a centromere
• 2. Duplication: a fragment joins to a homologous
chromosome
• 3. Translocation: a fragment joins to a nonhomologous chromosome
• 4. Inversion: a fragment reattaches itself to the
original chromosome in reverse order
Another source of duplications &
deletions
• Crossing over error can also cause
duplications and deletions
• Crossovers are usually reciprocal, but
occasionally one sister chromatid gives up
more genes than it receives
• One sister chromatid ends up with a
duplication (extra genes) and the other ends
up with a deletion (missing genes)
Effects of chromosome alteration
• Homozygous deletions (including having only
one copy on the X in males ) are usually lethal
• Duplications and deletions tend to have effects
of traits being deleted or missing
• Translocations and inversions can have position
effects
• Position effect: influence on a gene’s
expression because of its location among
neighboring genes
In humans
• Down Syndrome: 1 in 700 births in the US
–
–
–
–
–
–
–
Trisomy 21
Characteristic facial features
Short stature
Heart defects
Susceptibility to resp. infections
Mental retardation
Prone to leukemia
• Patau Syndrome: 1 in 5,000 births in US
–
–
–
–
Trisomy 13
Serious eye, brain, circulatory defects
Cleft palate
Babies rarely survive more than a year
• Edwards Syndrome:1 in every 10,000 births
– Trisomy 18
– Affects almost every body organ
– Babies rarely survive more than a year
When it happens to sex
chromosomes
• XXY (Klinefelter syndrome)
– Occurs once in every 2000 live births
– Male sex organs, but testes are abnormally small and
sterile
– Breast enlargement and other female char.
• XYY (extra Y)
• No well-defined syndrome, but men are usually
taller in stature
When it happens to sex
chromosomes
• XXX (trisomy X)
– 1 in 1000 live births
– Cannot be distinguished from XX females
• X0 (Turner syndrome)
– 1 in 5,000 live births
– Phenotypically female, but sex organs do not mature
at adolescence & secondary sex char. fail to develop
– Short in stature and are sterile
Other problems
• Cri du chat syndrome:
–
–
–
–
–
–
Cry of the cat
Caused by a deletion in chromosome 5
Mental retardation
Small head with unusual facial features
Cry that sounds like mewing of a cat
Usually die in infancy or early childhood
Genomic Imprinting
• The expression of some traits may depend
upon which parent contributes the alleles
for those traits.
• Two different genetic disorders, for
example, are caused by the same deletion
on chromosome 15.
• The symptoms differ depending upon
whether the gene was inherited from the
mother or the father.
• Prader-Willi syndrome is caused from the deletion
on the paternal chromosome 15.
• -char. by mental retardation, obesity, short stature,
and unusually small hands and feet
• Angelman syndrome is caused by the deletion on
the maternal chromosome 15.
• -char. by uncontrollable spontaneous laughter,
jerky movements, and other motor and mental
symptoms
• This leads us to believe that homologous
chromosomes are somehow marked or imprinted
differently, which causes them to function
differently in offspring
Genomic Imprinting (cont)
• genomic imprinting: process that induces intrinsic
changes in chromosomes inherited from males and
females
• It causes certain genes to be differently expressed
in the offspring depending upon whether the alleles
were inherited from the ovum or the sperm cell.
• In the new generation, the imprints are reversed in
the gamete-producing cells & are recoded
according to the sex of the new individual
• DNA methylation MAY be one mechanism for
genomic imprinting
Fragile-X and Triple Repeats
• Sections of DNA where a specific triplet of
nucleotides is repeated many times is called
a triple repeat
• They occur normally within many places on
the DNA (human genome)
• Progressive addition of triplet repeats can
lead to genetic disorders such as Fragile X
syndrome or Huntington’s disease
Fragile-X and Triple Repeats
• Fragile-X syndrome affects 1 in every 1500 males
and 1 in every 2500 females
• It is the most common cause of mental retardation
• An abnormal X chromosome, called a “fragile-X”
has the tip of the chromosome hanging onto the
rest of the X chromosome by a thin DNA thread
• The altered region of the chromosome (as well as
the normal version of that same region) contains
numerous triple repeats
• The triplet repeat CGG is repeated up to 50
times on one tip of a normal X
chromosome, but is repeated more than 200
times in a fragile-X chromosome
• Abnormal addition of triple repeats occurs
incrementally over generations, so there is a
“prefragile-X” condition between 50-200
CGG repeats
• These individuals are phenotypically
normal, but symptoms appear as more CGG
repeats are added in later generations.
1 µm
Figure 15-7
Page 301
Defective allele
Fragile site
CGG repeats
(200 to more than
1000 times)
Defective allele
CGG repeats
(up to 50 times)
Normal allele
Fragile-X and genomic imprinting
• Fragile-X syndrome’s complex expression may
be a consequence of maternal genomic imprinting
• Maternal imprinting explains why fragile-X
disorder is more common in males. (males only
inherit their X from their mother)
• Females can inherit the fragile-X from either
parent, but only the maternal version causes
expression of the syndrome. Heterozygotes have
partial protection and are usually only mildly
retarded.
Huntington’s and triple repeats
• Huntington’s disease is another example of
how extended triple repeats and genomic
imprinting can influence the expression of a
human genetic disorder
• The Huntington’s locus is near the tip of
chromosome 4 and has a CAG extended
triple repeat
• The triple repeat is more likely to extend if
the allele is inherited from the father
Extranuclear genes
• There are some exceptions to the chromosomal
theory of inheritance:
• Genes found in the cytoplasmic organelles such
as plastids or mitochondria are not inherited in
a Mendelian fashion, because they are not
distributed by segregating chromosomes during
meiosis
• Offspring only receive maternal cytoplasmic
genes in both plants and mammals