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 This i
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Chromosomal Mutations
• Any change in the structure or
number of chromosomes
• Large scale: Affect many genes
5 Types
1. Deletion
2. Duplication
3. Inversion
4. Translocation
5. NonDisjunction
Chromosomal Deletion
One or more genes are removed
Causes:
Wolf-Hirschhorn syndrome (severe mental retardation)
cri du chat syndrome (mewing sounds, mental retardation)
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 pallate, 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”
Trisomy 21 - Down Syndrome
Genetic Screening - Amniocentesis
KEY POINT #1
Too much or too little DNA is bad!
Let’s Review
What are the 4 types of
chromosomal aberrations?
Which type of aberration is probably
the most damaging?
Onto gene mutations!
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
• Causes: 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
• Causes: 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
• or 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
• Mutant proteins are trouble!
– They do not go where they are
supposed to go
– They do not do what
they are supposed to do
Example: Sickle Cell Anemia
Normal Red Blood Cell Sickle Red Blood Cell
• Red blood cells shaped • Red blood cells form an
like a disc abnormal crescent shape
• Hemoglobin (protien) • Hemoglobin (protein) is
carries oxygen to all parts abnormally shaped
of the body • don't move easily through
your blood vessels
• form clumps and get
stuck in the blood vessels
Example: Cystic Fibrosis (CF)
• What is it?
– Autosomal, recessive
disorder
• Symptoms
– Thick mucus in the lungs and digestive
track
– Constant lung infections and impaired
digestion
Cystic Fibrosis (CF)
• Who gets it?
– Anyone
– 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
Normal CFTR protein:
Ion channel in cell membrane
KEY POINT #2
Mutation of a gene = Mutant protein
Dysfunctional proteins cause the
symptoms of the disorder
Review
• What are the two major types of
genetic mutations?
• How are chromosomal aberrations
and gene mutations different?
• What are the 4 types of chromosomal
aberrations?
• What are some types of gene
mutations?
