MUTATIONS
MUTATION
• A mutation, the original source of
genetic variation caused by a change
in a DNA base or a chromosome.
Spontaneous mutations are those
that appear without explanation,
while induced mutations are those
attributed to a particular mutagenic
agent.
Mutations
• Mutation – a change
in the DNA message
• Mutations cause the
wrong protein to be
made (they may no
longer be functional)
• Mutations can have harmful, beneficial, neutral, or
uncertain effects on health. Mutations that cause
serious disability early in life are usually rare
because of their adverse effect on life expectancy
and reproduction.
• On rare occasions, a mutation results in a new
characteristic which can help the organism survive
in unfavourable environmental conditions. The new
characteristic will be passed to its offspring who can
survive where others may die. This is an example of
how natural selection and, over a long period,
evolution, occurs.
The pathogenic mutation alter genetic
component and may lead to genetic diseases:
• Single gene disorder : component of single
gene are altered.
• Chromosomal disorders: when the number of
chromosome (numerical) or structure
(structural) of chromosome is altered.
GENE MUTATION
• Mutations in a gene's DNA sequence can
alter the amino acid sequence of the protein
encoded by the gene.
• Gene mutations inherited from a parent or
acquired during a person’s lifetime.
• Mutation inherited as autosomal dominant,
autosomal recessive ,or X-linked traits.
I-
Sickle cell disease
• Sickle cell disease is a human genetic disorder. It results from
a single base change in the gene for B-globin. The altered
base cause insertion of the wrong amino acid into one
position of B globin protein. This altered protein results in
distortion of red blood cells under low oxygen conditions.
• Normal Hb A gene
…CTC…
…GAG
Sickle cell Hb S gene
…CAC…
…GTG…
…GAG…
mRNA
…GUG...
…Glu…
Protein
…Val….
Sickle cell anaemia
– A mutation caused a GAG codon to change into a
GUG codon in the gene for one of the protein
chains of hemoglobin
– mutation replaced the glutamic acid a2 with valine
– Conseqences = hemoglobin stick together and
causes damage to RBC = anemia
– The mutation also gives some resistance to malaria
in individuals with one sickle gene and one normal
gene
Autosomal recessive
• AlbInism = the lack of pigmentation in skin,
hair, and eyes
• 1) the lack of enzyme along the melaninproducing pathway;
• or 2) the inability of the enzyme to enter the
pigment cells and convert the amino acid
tyrosine into melanin.
Autosomal dominant
• Huntington’s disease - progressive
destruction of brain cells.
• The disease usually does not manifest until
after age 20-30.
• Polydactly is the presence of a sixth digit
common with this trait.
Sex linked
• Red-green colorblindness. 8% M, 0.04% F. X.
• Hemophilia- defective blood clotting protein
• Muscular dystrophy- DMD. 1 in 35,000.
Muscle wasting disease.
NUMERICAL ABNORMALITIES
Example
• Down Syndrome (Trisomy 21) (an
individual with Down Syndrome
has three copies of chromosome
21, rather than two).
• Turner Syndrome is an example of
MONOSOMY, where the individual
(female ) is born with only one sex
chromosome, an X.
Variation in chromosome
number
•
•
•
•
•
•
•
Aneuploidy = gain or loss one or more chr.
Monosomy = 2n – 1. eg. 45X
Trisomy = 2n + 1.
Euploidy = complete haploid set of chr (x)
Polypliody = more than 2 sets of chr.
Triploid = 3 sets
Tetraploid = 4 sets.
Klinefelter syndrome
•
•
•
•
•
•
•
•
Aneuploidy = Extra X chromosome (XXY).
2 in 1000 male births. Lower incidence that 47XXY
Sex ? Intersexuality
Male genitalia and internal ducts but testes
rudimentary and X produce sperm.
Tall, long arms/legs, large hands/ feet.
Gynecomastia and rounded hips.
Intelligence below normal range.
Y chromosome determines maleness.
• As XXY males enter puberty, they often don't make as
much testosterone as other boys. This can lead to a
taller, less muscular body, less facial and body hair, and
broader hips than other boys. As teens, XXY males may
have larger breasts, weaker bones, and a lower energy
level than other boys.
• By adulthood, XXY males look similar to males without
the condition, although they are often taller. They are
also more likely than other men to have certain health
problems, such as autoimmune disorders, breast
cancer, vein diseases, osteoporosis, and toothdecay.
• Between 95 percent and 99 percent of XXY males
are infertile because their bodies don't make a lot of
sperm.
XXX karyotype
• 47XXX. 1 in 1200 female.
• Extra X chr appears to disrupt the balance of
gen info needed for female developmt.
• Some may be normal, others may have
underdeveloped sex chrtc, sterility and mental
impairment.
• 48XXXX
• 49XXXXX.
Monosomy
• Turner syndrome 45X.
• 1 in 2000 female births.
• Female genitalia and internal ducts, ovaries
rudimentary.
• Short stature, broad chest, skin flaps back of
the neck, underdeveloped breasts.
• Sex ?.
Description
Normal Females
xx
Turner Syndrome Females
x
Wide and Webbed
Neck
Swollen Feet
Short Structure
Shortened
meta
carpal
Small
Finger
Nails
Loss of Hair
Shortened 4th &
5th Meta Carpal
TRISOMY 18
• Edwards syndrome = Trisomy 18
• Infants smaller than average newborn.
• Congenital malf, death within 4 mths.
(Pneumo)
KARYOTYPE
BABIES WITH EDWARDS SYNDROME
DOWN’S SYNDROME
Down Syndrome (Trisomy 21)
Down syndrome is the most common
cause
of
mental
retardation
and
malformation in a newborn.
It occurs
because of the presence of an extra 21st
chromosomes.
It was first described in 1866 by
Dr.John. L.H. Down, an English Physician.
Incidence
Down syndrome occurs about once in
every 800 births.
It is estimated that
10,000 children are born with down
syndrome each year in the India.
Causes

increased maternal age



Parents with chromosomal disorders
Hereditary
Chromosomal mutation
Karyotyping
CLINICAL MANIFESTATIONS
Mangolion Face
Simian Crease
Flattened Nose and Face,
Upward Slanting Eyes
Short Fifth
Finger that
curves
inward
Increased
space
between
1st and
2nd toe
Evolution
• In biology, evolution is the process of change in the inherited traits of a
population of organisms from one generation to the next.
• Mutations in genes can produce new or altered traits in individuals,
resulting in the appearance of heritable differences between organisms,
but new traits also come from the transfer of genes between
populations, as in migration, or between species, in horizontal gene
transfer, In species that reproduce sexually, new combinations of genes
are produced by genetic recombination, which can increase the variation
in traits between organisms.
• Evolution occurs when these heritable differences become more
common or rare in a population .