Download ChromosomeMutations

Chromosome Mutations
This image is called a karyotype. It shows human chromosomes.
Is this a girl or boy?
Types of Chromosome Mutations
1. Deletion: Occurs when a piece of
chromosome breaks off, resulting in the loss
of some genes.
Ex: “cri du chat” syndrome is a
deletion in the fifth largest
chromosome.
http://www.youtube.com/watch?v=NoNj6IlqrDY&safe=active
2. Duplication: (Addition) This is when a piece
of chromosome breaks off and attaches to a
homologous chromosome. The homologous
chromosome will have some genes repeated.
Ex: fragile X syndrome in males (there are 700
repeats)
http://www.youtube.com/watch?v=9_PEW6oc
SNs&safe=active
3. Inversion: This occurs when a piece of
chromosome is rotated and thus reverses the
order of the genes in that segment.
• Some genes participate in a common function. If these
genes are separated by an inversion, they may not be
able to function properly.
Ex: This is believed to be the cause of some
forms of autism.
http://www.youtube.com/watc
h?v=jWKLK4FhbCA&safe=active
4. Translocation: This is the transfer of a part of
a chromosome to a non-homologous
chromosome.
Ex: Some forms of cancer such as leukemia and
some forms of Down’s syndrome.
http://www.youtube.com
/watch?v=eUZYACO236c
&safe=active
5. Nondisjunction: This is the addition or loss of
a whole chromosome and occurs during
meiosis.
• In this case homologous chromosomes or sister
chromatids stay together.
There are two types:
1. Trisomy
2. Monosomy
Trisomy - a cell has one extra
chromosome.
Ex: Down’s syndrome (trisomy
21) and Klinefelters syndrome
(XYY).
Monsomy - a cell is missing
one chromosome.
Monosomy is usually lethal.
Why?
(Because the cell lacks genetic material)
Ex: Turner’s syndrome (XO)
http://www.youtube.com/w
atch?v=EA0qxhR2oOk&safe
=active
6. Polyploidy: The condition that results in an
organism having an extra set of chromosomes.
• This occurs when a nucleus does not undergo the
second meiotic division.
• The gametes become 2n instead of n.
• The zygote becomes 3n. This is common in plants but
lethal in animals.
Human Genetic Diseases
• There are three primary ways that the error
can be inherited (passed from generation to
generation).
1. Sex-linked inheritance
2. Dominant inheritance
(includes codominant and incomplete dominance)
3. Recessive inheritance
Sex-Linked Disorders
• Occurs due to errors in chromosome pair 23
(the sex chromosomes).
• These genetic diseases occur only in males.
• Since males have an XY sex chromosome any problems
with the X chromosome causes a genetic disease
• In females, which have XX chromosome any issue with
an X chromosome is hidden by the other X.
• Females can be carriers for the genetic disease, but not
develop the disease themselves
Examples of sex-linked genetic diseases
a. hemophilia--a disease in which the blood has
less than 1% of the normal clotting factor.
b. color-blindnessIn red-green colorblindness (The most
common form) reds and
greens are seen as
gray.
c. Muscular Dystrophy: There is slow but
progressive degeneration of muscle fibers.
• In Duchenne’s muscular dystrophy, individuals are
unable to walk by age 12 and normally die in their
teenage years through a chest infection or heart failure.
Usually below average intelligence.
Dominant Inheritance
• One bad gene from either parent will cause
the genetic disease.
• Since only one bad gene causes the disease, if either
parent has the disease the chance of the child
inheriting the bad gene and developing the disease is
50% with each conception.
• An example of a dominant genetic disease is
Huntington's Disease.
• Huntington’s disease produces involuntary
twitching and other involuntary movements.
• Huntington's usually has its onset when a
person is in their forties.
• It is characterized by a deterioration of parts
of the central nervous system which affect
both muscle control and behavior.
• Progeria is rare disorder that results in
accelerated aging. It is a random and
spontaneous mutation of one gene that is
dominant over its normal partner.
Codominant Inheritance
(Must have two dominant alleles)
• Sickle-cell disease- a blood
disease in which some of their
hemoglobin is abnormal
• The sickle-shaped red blood cells
clog the capillaries so that cells
cannot get needed oxygen and
nutrition.
• Sickle-cell disease is treated by
blood transfusions, pain killers and
chemicals which increase the
oxygen carrying capacity of the
blood.
Incomplete Dominance Inheritance
• Familial hypercholesterolemia
(FH): A disease that causes
high cholesterol.
• People with this disease do NOT
have as many LDL receptors on their
cells, which means less LDL’s can be
taken up by cells and build up in the
artery walls leading to
atherosclerosis (plaque build-up).
• Heterozygous individuals often have
heart attacks by age 35.
• Homozygous recessive individuals
have heart attacks by the age of
two.
Recessive Inheritance
• Both parents must have the defective gene in
order for the disease to be seen.
• The parents usually don't have the disease,
but carry the defective gene.
Autosomal Recessive Genetic Diseases
a. Cystic Fibrosis- a disease that affects various
glands, such as mucus, salivary and sweat
glands.
•
•
•
It is diagnosed by the sweat test.
Over-active mucus glands give these people chronic
respiratory problems.
Death usually occurs in early twenties unless treated
with lung transplants.
b. phenylketonuria (PKU)-a disease of
metabolism in which the child cannot
metabolize phenylalanine (an amino acid)
• To control the effects of the disease they must avoid
this amino acid in their diet.
• Since phenylalanine is in aspartame(NutraSweet),
warning labels appear on soft drinks which are
sweetened with this product.
• If ignored, they can become severely mentally
handicapped within months. Infants are routinely
tested for PKU.
c. Tay-Sachs disease -a recessive genetic disease
in which the child cannot metabolize a certain
lipid (fat).
• These lipids surround the CNS and prevent the brain
from expanding.
• They become blind and mentally handicapped. Death
occurs in early childhood.
Chromosomal Disorders
a. Klinefelter's Syndrome--occurs only in males
when the male child receives an XXY sex
chromosome combination instead of the normal
XY.
•
•
•
•
Klinefelter's affects sexual development (small testicles, do
not produce normal amounts of testosterone)
Klinefelter's boys have an incomplete puberty and a childlike appearance.
They will not grow facial hair and will show some breast
development.
Klinefelter's is often accompanied by mental deficiency or
mental retardation.
b. Turner's Syndrome - occurs when the female
child receives only a single X sex chromosome
instead of the normal XX combination
(monosomy 23).
• Turner's girls have retarded sexual development, are
sterile, have a webbed neck, and have very specific
mental deficiencies involving visual recognition and
spacial arrangements. There are external genitalia but
no ovaries. There are heart, kidney and skeletal
defects.
c. XYY condition or Jacobs syndrome--a form of
trisomy 23 that occurs only in males.
• In the past, XYY males were called "super males,"
because they are abnormally tall, abnormally strong
and abnormally aggressive.
d. Down's Syndrome--a
form of trisomy in
which there is an extra
chromosome at 21.
• Down's effects either sex,
and is usually
accompanied by
moderate to severe
mental retardation.
• They often have heart
defects and are
susceptible to infections.
e. Triple X syndrome -- These individuals are
called metafemales. They have limited fertility
but are otherwise normal.
Detecting Genetic Disorders
1. Amniocentesis
• A sample of the amniotic fluid can be removed
using a needle and examined for genetic
abnormalities.
• The cells are placed in a nutrient-rich medium
and allowed to multiply for a few weeks to
provide a large enough sample to be karyotyped
• This procedure can not be done prior to the fourteenth week
due to risk to the fetus.
2. Fetoscopy
• An endoscope is inserted into a small incision
in the mother’s abdomen.
• The endoscope has a camera to view the fetus
and can also be used to take samples or
perform operations.
• Used to remove excess fluid around the brain,
provide fetal blood transfusions and collect
blood samples for karyotyping or to determine
blood type.
3. CVS (chorionic villi sampling)
• This procedure can be done as early as the
ninth week of pregnancy.
• Cells are removed from chorion. These cells
are derived from the fetus.
• The cells are grown in a medium and later
karyotyped
4. Karyotyping
• A cell undergoing mitosis is photographed.
The photograph is enlarged and the
chromosomes are cut out and arranged in
pairs to examine any abnormalities.
5. DNA Probe:
• Radioactive synthetic DNA is mixed with DNA
from a suspected carrier.
• The DNA is complementary to the known
mutated gene and will pair with the human
gene if it is defective.
• If the person is a carrier then the human DNA
will become radioactive.
• Ex: sickle cell anemia, cystic fibrosis, muscular
dystrophy, hemophilia, phenyketonuria.
6. Genetic Markers
• This is any characteristic that provides
information about an organism’s genome
• A known DNA sequence that lies close to the
disease causing gene is called a linked marker.
It does not affect the gene but is always found
near it. Ex: Huntington’s Disease.
• A gene-specific marker is a sequence of DNA
that is part of the gene itself. These markers
always indicate the presence of the gene
causing the disorder.
Treatments of Genetic Disorders
1. Screening and Prevention
• There are routine blood tests done at birth to
determine the presence of genetic
disorders.(Ex: phenylketonuria)
2. Surgery
• Cleft palates can be fixed
using reconstructive surgery
3. Environmental Control
• This can be done to minimize the effects of
the symptoms.
• Ex: albinos lack the pigment melanism and
should limit their exposure to direct sunlight.
4. Gene Therapy
• Normal or modified genes are transferred to
the defective cell and enable it to properly
produce the original defective protein.
• This is still experimental
• Ex: Spina bifida can be treated by inserting a
tube leading from the brain to the digestive
tract so that fluid can be released and prevent
mental retardation.
Genetic Counseling
• Genetic counselors study the medical histories of
couples and their families and advise them of the
frequency of disorders and risk factors associated
with their particular case. They will normally
construct a pedigree of their family history.
• Couple are considered to be of high risk if they
already have a child with a genetic disorder, a
family history of genetic disease and if the
woman is over the age of 35.
Question:
What are the ethical considerations of genetic
engineering and genetic counseling?
Human Genetics and Pedigree Analysis
Pedigrees: Family Trees
• One of the central tasks of the human
geneticist
• Pedigree analysis is the construction of family
trees
• A pedigree is used to trace inheritance of a
trait over several generations.
Three primary patterns of inheritance:
1.autosomal recessive
2.autosomal dominant
3.sex-linked (X-chromosomal)
Symbols used in pedigree charts:
Autosomal Recessive Pedigree
• Recessive: If neither parent has the
characteristic phenotype (disease) displayed
by the child, the trait is recessive.
• Autosomal: Gene is on one of the autosomes
(Chromosomes 1-22). Male and female
offspring equally likely to inherit trait.
A typical pedigree:
Worksheet:
The Perils of Inbreeding: A Case Study in
Saudi Arabia
Autosomal Dominant Pedigree
• Dominant: Affected individuals can appear in
every generation
• Autosomal: Gene is on one of the autosomes
(Chromosomes 1-22). Male and female
offspring equally likely to inherit trait.
• A trait that appears in successive generations
is normally due to a dominant allele.
Sex-Linked Pedigree
• X-linked: The trait is preferentially seen in
males, who are hemozygous. Females are
heterozygous "carriers"
• Most X-linked traits are recessive.
• Ex: Inheritance of red-green color blindness
Practice Multiple Choice