Download Genetic Mutations

Human Genetic
Mutations
2 Main Types of Mutations
1.) Chromosomal Mutations
2.) Gene Mutations
What are chromosomes?
• Humans have 23 pairs
of chromosomes, with
one chromosome from
each parent.
• The chromosomes are
coiled up DNA.
• Under normal
conditions all of the
chromosomes are
inherited in tact.
Chromosomal Mutations
• Any change in the structure or
number of chromosomes
• Large scale: Affect many genes
5 Types
1.
2.
3.
4.
5.
Deletion
Duplication
Inversion
Translocation
NonDisjunction
Chromosomal Deletion
One or more genes are removed
Causes:
Wolf-Hirschhorn syndrome (severe mental retardation)
cri du chat syndrome (meowing sounds, mental retardation)
Wolf-Hirschhorn syndrome
(WHS) refers to a condition
that is caused by a missing
part (deletion) of the short
arm of chromosome 4.
Chromosomal Duplication
A segment of genes is copied twice and added to
the chromosome
Causes:
Charcot–Marie–Tooth disease
(high arched foot, claw feet, confined to a wheelchair)
Chromosomal Inversion
a segment of genes flip end-to-end on the chromosome
Causes:
Four-Ring Syndrome
(cleft palate, club feet, testes don’t descend)
Chromosomal Translocation
Material is swapped with another chromosome
Causes:
Burkitt’s Lymphoma
(cancer of the lymph nodes, in children)
Nondisjunction
• Chromosomes FAIL TO
SEPARATE during meiosis
• Meiosis I Nondisjunction
• Meiosis II Nondisjunction
Nondisjunction
• Produces gametes (and therefore a
baby) with one missing
chromosome or one extra
chromosome
Nondisjunction (in Meiosis II)
Fertilization
Nondisjunction
• Every cell in that baby’s body will have __
copies of this chromosome instead of___.
• This condition is called ____________.
• Trisomy 21 = Individual has _____ copies
of chromosome # ________
Nondisjunction
• Every cell in that baby’s body will have 3
copies of this chromosome instead of 2.
• This condition is called __________.
• Trisomy 21 = Individual has _____ copies
of chromosome # ________
Nondisjunction
• Every cell in that baby’s body will have 3
copies of this chromosome instead of 2.
• This condition is called TRISOMY
• Trisomy 21 = Individual has __ copies of
chromosome # ____.
Nondisjunction
• Every cell in that baby’s body will have 3
copies of this chromosome instead of 2.
• This condition is called TRISOMY
• Trisomy 21 = Individual has 3 copies of
chromosome # 21.
Chromosomal Mutations
• Most chromosomal mutations are
lethal
• If the fetus survives: Tend to cause
wide-spread abnormalities
• Example:
Down Syndrome
Down Syndrome
• Cause:
Nondisjunction of
chromosome 21
• Three copies of chromosome 21 =
“TRISOMY 21”
• One in every 691 babies in the the United
States is born with Down syndrome, making
Down syndrome the most common genetic
condition.
• Short stature (height)
• Low muscle tone
• A short, wide neck.
• Slanted eyes.
• Irregularly shaped mouth and tongue.
• Intellectual disability
• Heart defects
Genetic Screening - Amniocentesis
Karyotypes
• A pictorial display of metaphase
chromosomes from a mitotic cell
• Homologous chromosomes- pairs
• Chromosomes pairs 1-22 are called
autosomes
• Chromosome pair 23 are called the sex
chromosomes
Trisomy 21 - Down Syndrome
Klinefelter’s Syndrome
• Due to
nondisjunction
• Chromosome
makeup is XXY
• Creates a sterile
male
Turner’s Syndrome
• Due to nondisjunction
• Monosomy- the condition in which there is
a missing chromosome.
• Sex chromosome make up is X only
• Females that will not undergo puberty.
Edward’s Syndrome
• Due to
nondisjunction
• Extra number 18
chromosome
(trisomy 18)
• Traits: Low ears,
kidney and heart
defects
Patau’s Syndrome
• Extra number 13
chromosome
(trisomy 13)
• Traits: Deformed
eyes, ears and
lips, polydactyly
(extra fingers or
toes)
KEY POINT #1
Too much or too little DNA is bad!
Gene Mutations
• Small scale: one gene
is affected
• Any change to the DNA
sequence of a gene:
Nucleotides/Bases may be
added, missing, or
changed
Gene Mutations: 2 Types
Point Mutation
Frameshift Mutation
Point Mutation
• One base (A, T, C, or G) is substituted for another
• Can Cause: Sickle-cell anemia
• 3 Possible Consequences:
– nonsense mutations: code for a stop, which can
translate the protein
– missense mutations: code for a different amino
acid
– silent mutations: code for the same amino acid
Frameshift Mutation
• One or more bases (A, T, C, or G) are
added or deleted
• Can Cause: Cystic Fibrosis
• Caused by:
– Insertion: adding a base
– Deletion: removing a base
Causes of Mutations
• spontaneous
• occur during DNA replication
• Caused by MUTAGENS
• physical ex: radiation from UV rays, X-rays or
extreme heat
• chemical (molecules that misplace base pairs or
disrupt the helical shape of DNA).
Gene Mutations
• KEY IDEA: A mutated gene will make a
mutated protein
Example: Sickle Cell Anemia
Normal Red Blood Cell
• Red blood cells shaped like a disc
• Hemoglobin (protien) carries oxygen to all parts of the
body
Sickle Red Blood Cell
•
•
•
•
•
•
Red blood cells form an abnormal crescent shape
Hemoglobin (protein) is abnormally shaped
don't move easily through your blood vessels
form clumps and get stuck in the blood vessels
Mutation located on Chromosome 11
Effects mostly African Americans
Example: Cystic Fibrosis (CF)
• What is it?
– Autosomal, recessive
disorder found on
Chromosome 7
• Symptoms
– Thick mucus in the lungs and digestive
track
– Constant lung infections and impaired
digestion
Cystic Fibrosis (CF)
• Who gets it?
– Most common in Caucasians
• Prevalence
– 1 in ~3,000 Americans has CF
– 1 in 23 white Americans carries the
mutant allele!
Cause of Cystic Fibrosis (CF)
• The “CFTR” gene is mutated
– 3 base pairs are deleted
• Mutant protein is missing an amino acid
and cannot fold correctly
vs
Albinism
• Due to the lack of
the pigment
melanin (a protein)
in the skin, eyes,
and hair.
Hemophilia
• Disorder that is
linked to the sex
chromosomes
• Missing a protein
needed for the
blood to clot
Tay-Sachs Disease
• Inability to
synthesize an
enzyme that
prevent lipid
buildup in brain
cells.
• Causes the
breakdown of
nervous system
Phenylketonuria (PKU)
• Inability to code for
an enzyme needed
for changing the
amino acid
phenylalanine to
tyrosine.
• Damages brain
cells and causes
mental retardation.
Duchenne Muscular Dystrophy
• Linked to the sex
chromosomes
• Results in the
progressive
weakening and
loss of skeletal
muscle.
Colorblindness
• Carried on the X of
the sex
chromosomes.
• Occurs more
frequently in males
than females.
KEY POINT #2
Mutation of a gene = Mutant protein
Dysfunctional proteins cause the
symptoms of the disorder