Transcript MUTATIONS

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MUTATIONS
Changes in DNA that affect genetic
information
 Genes are located on chromosomes
 Genes inherited from mom and dad
Gene Mutations
 Point Mutations – changes in
one or a few nucleotides
 Substitution
 THE FAT CAT ATE THE RAT
 THE FAT HAT ATE THE RAT
 Insertion
 THE FAT CAT ATE THE RAT
 THE FAT CAT XLW ATE THE RAT
 Deletion
 THE FAT CAT ATE THE RAT
 THE FAT ATE THE RAT
Gene Mutations
 Frameshift Mutations – shifts
the reading frame of the
genetic message so that the
protein may not be able to
perform its function.
 Insertion
 THE FAT CAT ATE THE RAT
 THE FAT HCA TAT ETH ERA T
 Deletion
H
 THE FAT CAT ATE THE RAT
 TEF ATC ATA TET GER AT
H
Your cells have autosomes
and sex chromosomes.
• Your body cells have 23 pairs
of chromosomes.
– Homologous pairs of
chromosomes have the
same structure.
– For each homologous pair,
one chromosome comes
from each parent.
• Chromosome pairs 1-22 are
autosomes.
• Sex chromosomes, X and Y,
determine gender in mammals.
Chromosome Mutations
 Changes in number and structure of entire
chromosomes
 What do scientists use to identify these
type of mutations?
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Original Chromosome
Deletion
Duplication
Inversion
Translocation
ABC * DEF
AC * DEF
ABBC * DEF
AED * CBF
ABC * JKL
GHI * DEF
Karyotypes
 a set of photographs of chromosomes grouped
in order in pairs from one cell.
 What are some observations we could make
from this karyotype?
Male vs. Female
 Males have XY sex chromosomes.
 Females have XX sex chromosomes
 The Y chromosome carries very few genes
essential for life.
 The X chromosome is a much longer DNA
molecule and contains many, many genes
that are needed for cells to function.
Karyotype Notation
 A short-hand way to write a person’s
karyotype.
 Total # of chromosomes, sex
chromosomes, extra or missing
chromosomes
 Normal Female
 46XX
 Normal Male
 46XY
Karyotype Notation
Significance of Mutations
1. Most are neutral
• Eye color
• Birth marks
2. Some are harmful
• Sickle Cell Anemia
• Down Syndrome
3. Some are beneficial
• Sickle Cell Anemia to Malaria
• Immunity to HIV
What Causes Mutations?
 There are two ways in which DNA can
become mutated:
1. Mutations can be inherited.
 Parent to child
2. Mutations can be acquired.
 Environmental damage
 Mistakes when DNA is copied
 Non-disjunction-failure of chromosomes to separate
properly during Meiosis.
 What are we making during Meiosis?
 In your own words what is a non-disjunction?
Genetic Disorders
 an illness caused by one or more
abnormalities in the genome, especially a
condition that is present from birth.
 Conditions may or may not be inherited.
 Mutations occur all the time in every cell in the body.
 Each cell, however, has the remarkable ability to
recognize mistakes and fix them before it passes them
along to its descendants.
 But a cell's DNA repair mechanisms can fail, or be
overwhelmed, or become less efficient with age.
Turners Syndrome
Caused by a nondisjunction, if a pair of sex chromosomes fails to separate
during the formation of an egg or sperm
• Affects1 in 2,500
newborns
• 45 chromosomes;
have only 1 X
chromosome
•#23 Monosomy
• girls fail to go thru
puberty
Turners Syndrome
•96-98% do not survive to birth
•stocky appearance
•short webbed neck
Other medical symptoms include:
•lymphedema (swelling of hands and
feet)
•heart and/or kidney defects
•high blood pressure
•infertility (inability to have children)
Cri-Du-Chat Syndrome
•These children have a deleted portion of chromosome number 5.
•Estimated 1 in
20,000-50,000
newborns
•Found in ALL
ethnic backgrounds
•Not inherited
•Can be XY or XX
•#5 Deletion
Cri-Du-Chat Syndrome
•Cry that is high-pitched and sounds
like a cat
•Downward slant to the eyes
•Low birth weight and slow growth
•Low-set or abnormally shaped ears
•Mental handicap (intellectual disability)
•Partial webbing or fusing of fingers or
toes
•Slow or incomplete development of
motor skills
•Small head (microcephaly)
•Small jaw (micrognathia)
•Wide-set eyes
WAGR Syndrome
•The condition results from a deletion on chromosome 11 resulting in
the loss of several genes
1 in 500,000 children
under age 15
7 in 1000 cases have
Wilms Tumor
46 chromosomes
XY or XX
#11 Deletion of upper
arm
Aniridia-Wilms Tumor Syndrome
•Predisposed to Wilms
kidney tumor
•Mentally handicapped
•Severe childhood
obesity
•Growth retardation
•Blindness
•Tumors on kidneys
•Short lifespan
•Missing the iris of the
eye
Thirteen Q Deletion Syndrome
600 cases worldwide
1st diagnosed 20 years ago
46 chromosomes
Affects XY or XX
#13 Deletion of lower arm
Thirteen Q Deletion Syndrome
Mentally retarded
Deformed face
No thumbs
Heart disease
Short lifespan
Prader-Willi Syndrome
Prader-Willi syndrome is caused by a gene missing on part of
chromosome 15. Normally, your parents each pass down a copy of this
chromosome. Most patients with Prader-Willi syndrome are missing the
genetic material on part of the father's chromosome.
1 in 15,000 live births
46 chromosomes
XY=97%
XX=3%
#15 Deletion of lower arm
Prader-Willi Syndrome
Low muscle tone
Short stature
Incomplete sexual development
Cognitive disabilities
Problem behaviors
Chronic feeling of hunger
Obesity
Shorter lifespan
Eighteen Q Deletion
Syndrome
1 in 40,000 newborns
Estimated 100 babies per year
46 chromosomes
XY or XX
#18 Deletion of lower arm
Eighteen Q Deletion Syndrome
Symptoms correlate with the size of the deletion
Mentally handicapped
Heart disease
Abnormal hands and feet
Large eyes
Large ears
Normal lifespan
Cat-Eye Syndrome
1 in 1,000,000 births
46 chromosomes
Affects XY or XX
#22 Deletion of bottom
arm
Cat-Eye Syndrome
•Normal to severe
malformations
•Fused fingers and toes
•Mentally handicapped
•Small jaw
•Heart problems
•Normal lifespan
Four-Ring Syndrome
1 in 10,000,000 births
46 chromosomes
XY or XX
#4 Inversion
Four-Ring Syndrome
Cleft palate
Club feet
Testes don’t descend
Short lifespan
Down Syndrome
1 in 31,000 births
46 chromosomes
XY=97%
XX=3%
#14/21 Translocation
Trisomy 21
Down Syndrome
1 in 850 newborns
Estimated 250,000
people are affected in
the US
47 chromosomes
XY or XX
#21 Trisomy
Nondisjunction
Down Syndrome
•Short, broad hands
•Stubby fingers
•Rough skin
•Impotency in males
•Mentally handicapped
•Cognitive delays
•Small round face
•Protruding tongue
•Short lifespan
•Increased risk of
developing Alzheimer
disease
Patau’s Trisomy
Syndrome
1 in 14,000 births
47 chromosomes
XY or XX
#13 Trisomy
Nondisjunction
Patau’s Trisomy Syndrome
Small head
Small or missing eyes
Heart defects
Extra fingers
Mentally handicapped
Cleft palate
Most die a few weeks after birth
Edward’s Trisomy
Syndrome
1 in 4,400 births
47 chromosomes
XX=80%
XY=20%
#18 Trisomy
Nondisjunction
Edward’s Trisomy Syndrome
Small head
Mentally handicapped
Internal organ abnormalities
90% die before 5 months of age
Jacob’s Syndrome
1 in 1,800 births
47 chromosomes
XYY only
#23 Trisomy
Nondisjunction
Jacob’s Syndrome
?
Normal physically
Normal mentally
Increase in testosterone
More aggressive
Normal lifespan
Klinefelter Syndrome
1 in 1,100 births
47 chromosomes
XXY only
#23 Trisomy
Nondisjunction
Klinefelter Syndrome
Scarce beard
Longer fingers and arms
Sterile
Delicate skin
Low mental ability
Normal lifespan
Triple X Syndrome
1 in 2,500 births
47 chromosomes
XXX only
#23 Trisomy
Nondisjunction
Triple X Syndrome
Normally physically
Normal mentally
Fertile
Short lifespan
Cystic Fibrosis (CF)
 Clogs the lungs and leads to lifethreatening lung infections.
 Obstructs the pancreas and stops natural
enzymes from helping the body break
down food and absorb vital nutrients
 Fluid in lungs, potential respiratory failure
 Common among Caucasians
 1 in 20 are carriers
 Therefore is it dominant or recessive?
Cystic Fibrosis (CF)
 Monogenic
 Cause: deletion of only 3
bases on chromosome 7
 Estimated in 30,000
children and adults in
the U.S.
 70,000 people
worldwide
Muscular Dystrophy
 X-linked or
autosomal genetic
disorder.
 Muscular dystrophy is
a disease in which the
muscles of the body
get weaker because of
a lack of a certain
protein
 Can be passed on by
one or both parents,
depending on the form
of MD
Symptoms:
•Muscle weakness that slowly gets
worse
•Delayed development of muscle
motor skills
•Difficulty using one or more muscle
groups
•Eyelid drooping (ptosis)
•Loss of strength in a muscle or
group of muscles as an adult
•Loss in muscle size
•Problems walking (delayed walking)
Huntington’s Disease
 Huntington's disease (HD)
is an inherited,
degenerative brain
disorder which results in
an eventual loss of both
mental and physical
control.
 The disease is also known
as Huntington's chorea.
Chorea means "dance-like
movements" and refers to
the uncontrolled motions
often associated with the
disease.
Hemophilia, the royal
disease
 Hemophilia is the oldest
known hereditary
bleeding disorder.
 Caused by a recessive
gene on the X
chromosome.
 There are about 20,000
hemophilia patients in
the United States.
 One can bleed to death
with small cuts.
 The severity of
hemophilia is related to
the amount of the
clotting factor in the
blood. About 70% of
hemophilia patients
have less than one
percent of the normal
amount and, thus, have
severe hemophilia.
ALS
(Amyotrophic Lateral
Sclerosis, or Lou Gehrig’s
disease)
 the disease strikes people between the
ages of 40 and 70, and as many as
30,000 Americans have the disease at
any given time
 This monogenic mutation is believed to
make a defective protein that is toxic to
motor nerve cells.
 A common first symptom is a painless
weakness in a hand, foot, arm or leg,
other early symptoms include speech
swallowing or walking difficulty
Designer Baby
 http://www.cbsnews.com/2100500165_162-4840346.html
Chromosome Mutations
 Cri-du-chat
 Deletion of material on 5th
chromosome
 Characterized by the cat-like
cry made by cri-du-chat
babies
 Varied levels of metal
handicaps
Sex Chromosome
Abnormalities
 Klinefelter’s
Syndrome
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XXY, XXYY, XXXY
Male
Sterility
Small testicles
Breast enlargement
Sex Chromosome
Abnormalities
 XYY Syndrome
 Normal male traits
 Often tall and thin
 Associated with antisocial and behavioral
problems
Sex Chromosome
Mutations
 Turner’s Syndrome
 X
 Female
 sex organs don't
mature at
adolescence
 sterility
 short stature
Sex Chromosome
Mutations
 XXX
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Trisomy X
Female
Little or no visible differences
tall stature
learning disabilities
limited fertility
What’s an Autosome?
 Autosome: refers to chromosomes 1-22
 Ex: Autosomal disorders: gene for the disease is found on
chromosomes 1-22
 Autosomal Recessive Inheritance
 Must inherit two copies of the disorder to be affected
 Healthy is dominant (HH or Hh)
 Disease is recessive (hh)
 Ex: Cystic fibrosis, PKU, Albinism, Sickle cell anemia
 Autosomal Dominance Inheritance
 Only need to inherit one copy of the disorder to be affected
 Disease is dominant (HH or Hh)
 Healthy is recessive (hh)
 Ex: Familial hypercholesterolemia (also called FH),
Huntington’s disease, Neurofibromatosis
Autosomal Dominance Inheritance
 Disease is dominant (FF or Ff)
 Homozygous dominant: early death and don’t survive to reproduce
 Heterozygous live into adulthood
 Healthy is recessive (ff)
 ex: Paul has familial hypercholesterolemia and Stacy is healthy.
The two have 3 children. After testing, the middle child is the
only healthy child.
Key
disease
disease
F = FH disease
f = healthy
healthy
healthy
Autosomal Dominance
Inheritance
 Huntington’s disease is a dominant disorder found on
chromosome 4. Betty and Marcus met at a support clinic they
have been attending to help them cope with the knowledge of
their illness with Huntington’s disease. They would like to know
the risk of having a healthy child, now that Betty is pregnant.
Key
disease
disease
H = Huntington’s disease
h = healthy
disease
healthy