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Chromosomal Mutations:Variation in
Chromosome Number
Henry County Professional Learning High School Session II
Chromosomal Mutations
• Deletion – part of the chromosome is missing
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Starts with breaks in the chromosome
Radiation, heat, viruses, chemicals, etc.
May cause an unpaired loop
May give rise to pseudodominance
Cri-du-chat syndrome (Chrom. #5)
Chromosomal Mutations
Chromosomal Mutations
• To "read" a set of chromosomes,
scientists use three key features
to identify their similarities and
differences:
• Size. This is the easiest way to
tell chromosomes apart.
• Banding pattern. The size and
location of Giemsa bands make
each chromosome unique.
• Centromere
position. Centromeres
appear as a
constriction. They
have a role in the
separation of
chromosomes into
daughter cells during
cell division (mitosis
and meiosis).
Chromosomal Mutations
• Genetic disorders resulting from chromosome deletions include:
• Cri-du-Chat Syndrome (Chromosome 5)
• Williams Syndrome (Chromosome 7)
What is Cri-Du-Chat syndrome?
 Cri-du-chat is a French term for “cry of the cat”
 Also known as 5p- syndrome
 Cri-du-chat syndrome occurs in an estimated 1 in
20,000 to 50,000 newborns
HOW COMMON IS CRI-DU-CHAT
Cri-du-chat syndrome occurs in an estimated 1 in 20,000 to 50,000 newborns
This condition is found in people of all ethnic backgrounds
Individuals with
Cri-Du-Chat
Centromere Position
Centromere Position
• The position of the centromere relative to the ends helps scientists
tell chromosomes apart. Centromere position can be described three
ways: metacentric, submetacentric or acrocentric.
• In metacentric (met-uh-CEN-trick) chromosomes, the centromere lies
near the center of the chromosome.
Centromere Position
• Submetacentric (SUB-met-uh-CEN-trick) chromosomes have a
centromere that is off- center, so that one chromosome arm is longer
than the other. The short arm is designated "p" (for petite), and the
long arm is designated "q" (because it follows the letter "p").
• In acrocentric (ACK-ro-CEN-trick) chromosomes, the centromere is
very near one end.
Chromosomal Mutations
• Duplication – doubling of a segment of a chromosome
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Tandem
Reverse tandem
Terminal tandem
Position Effect of barring eyes in Drosophila
Chromosomal Mutations
• Inversion – results when a segment of a chromosome is excised and
then reintegrated in an orientation 180 degrees from the original
orientation.
• Pericentric inversion
• Paracentric inversion
• Resulting from a dicentric bridge
Chromosomal Mutations
• Translocation – change in position of chromosome segments and the
gene sequences they contain to a different location
• Nonreciprocal intrachromosomal
• Nonreciprocal interchromaosomal
• Reciprocal interchromosomal
A Robertsonian
translocation occurs when the
long arms of two acrocentric
chromosomes fuse at a
centromere. The two short arms
are lost, leaving a total of 45
chromosomes. But because the
short arms carry very little
genetic information, individuals
with Robertsonian
translocations are usually
healthy.
Chromosomal Mutations
• Fragile Sites and Fragile X Syndrome
• Narrowings or unstained areas (gaps)
• Recessive X-linked traits (predominately males)
• Normal transmitting males carrying a premutation will have grandsons with
mental retardations and some granddaughters (up to 33%) with mild
retardation
Variation in Chromosomal Number
• Euploidy – the correct number of sets of chromosomes in an
organism
• Monoploidy – only one set of chromosomes when there should be
more
• Male wasps, ants, and bees are monoploids because they develop from
unfertilized eggs
• Used in plant-breeding experiments/colchicine (inhibits mitotic spindle)
Variation in Chromosomal Number
Polyploidy – having three or more sets of chromosomes
• Usually occurs due to a breakdown of the mitotic spindle
• Usually occurs in plants (self-fertilization)
• Even numbered polyploids have a better chance of being fertile than odd
numbered polyploids
• In humans, triploidy is usually lethal.
Variation in Chromosomal Number
Polyploidy (continued)
• Autopolyploidy
• All sets of chromosomes originate in the same species/defect in meiosis
• Example – a diploid gamete fuses with a haploid gamete to produce a triploid
zygote (bananas and seedless fruit)
Variation in Chromosomal Number
Polyploidy (continued)
• Allopolyploidy
• Sets of chromosomes originate from different species though usually related
• Because of differences between chromosomes, the hybrid, no crossing over
occurs and no viable gametes produced making hybrids sterile
• Occasionally, tow sets of different chromosomes will double, producing
tissues of 2N + 2N2 / produces fully fertile allotetraploid, 2N + 2N2, plants
Variation in Chromosomal Number
• Aneuploidy – variation in the number of chromosomes
• Nullisomy - loss of one homologous chromosome pair; 2N – 2
• Monosomy – loss of a single chromosome;
2N – 1
• Trisomy – single extra chromosome; 2N + 1
• Tetrasomy – extra chromosome pair; 2N + 2
Nondisjunction
Variation in Chromosomal Number
• In humans, Down Syndrome is the only disorder where an extra
autosomal chromosome exists and the individuals lives past three
months. All other embryos will self-abort or the infant will die within
6 months. However, extra sex chromosomes will not cause an
embryo to necessarily abort; but the individual may have other
distinguishable characteristics.
Variation in Chromosomal Number
• Trisomy-21 – Down Syndrome
• Trisomy-13 (Patau syndrome) – cleft lip and palate, small eyes,
polydactyly and mental retardation. Dies within 3 months
• Trisomy-18 (Edwards syndrome) – developmental retardation,
congenital malformations, and die within 6 months
Klinefelter
• Dr. Harry Klinefelter
• Massachusetts General Hospital in Boston
• 1942 symptoms first identified
• 1950’s syndrome was discovered
• Early 1970’s screening of infants began
About The Disorder
• Sex Chromosomes are XXY
• May display all or none of the symptoms
• Some live their entire lives without any suspicion that anything is
wrong
• Is not passed through genetics
Male with
Klinefelter’s
Syndrome
Common Symptoms
Diagnosis
• Hormone Testing
• Semen analysis
• Usually not diagnosed before puberty
• Can be detected prenatally by amniocentesis or chorionic villus
sampling
Karyotype
Treatment
• Testosterone can be injected or administered through as skin patch or
gel
• Usually continues throughout the lifespan
• Does not help with reproduction
Marfan Syndrome
• French Physician Antoine Bernard- Jean
Marfan
• Discovered in 1896
• He described a five year old girl with
abnormally long and frail limbs and
fingers and lots of other skeletal
abnormalities.
Cause of Disorder
• Marfan Syndrome is caused by a defect in a gene
• It is a disorder that affects connective tissue in the body
• Connective tissue is what provides our body strength
and flexibility to structures of out body such as:
• Bones
• Ligaments
• Muscles
• Blood Vessels
• Heart Valves
Chromosomes Involved
• This disorder is located on chromosome 15
• Chromosome 15 controls the production of the protein
fibrillin
• Fibrillin is responsible for elasticity and strength of connective
tissue
• The mutations that cause Marfan Syndrome change a single
amino acid in the fibrillin-1 protein.
• Researchers found more than 1,300 Fibrillin-1 gene mutations
that cause this disorder
Complications
• Aortic Aneurysm
• Aortic Dissection
• Valve Malformation
• Lens Dislocation
• Retinal Problems
• Early-onset Glaucoma or Cataracts
Treatments
• Special medicines called beta blockers and ARBs
(angiotensin-receptor blockers) which work to lower
the blood pressure and reduce wear and tear on the
blood vessels.
• Teens with Marfan syndrome that develop scoliosis
have to wear a special back brace.
• Calcium channel blockers are recommended if the
patient can not take beta blockers.
• Regular follow up appointments.
• Routine cardiovascular, eye, and orthopedic exams.
Michael
Phelps
Jonathan Larson
Abraham Lincoln
Famous People
Affected By Marfan
Jacobs syndrome (47, XYY)
• In 1961 Dr. Avery Sandberg and
associates at the Roswell Park
Memorial Institute observed for
the first time ever a man who
had a karyotype of XYY.
• The subject was a 44 year old
man who had sought the help of
a geneticist after having a
daughter who suffered from
down syndrome.
• XYY syndrome is a condition
when a male patient acquires an
extra Y chromosome in addition
to the normal one X and one Y
chromosomes. It is often argued
whether the term ‘syndrome'
should be used in connection to
the XYY condition since the
patients' phenotypes are normal
and they do not have knowledge
of their karyotype.
XYY Occurences
• 47 XYY syndrome is not an inherited
condition. This is just the result of an
accidental event during sperm cell formation.
The ‘accident' happens either during
metaphase I or metaphase II.
• An error in cell division called nondisjunction
can result in sperm cells with an extra copy of
the Y chromosome. If one of these atypical
reproductive cells contributes to the genetic
makeup of a child, the child will have an extra
Y chromosome in each of the body's cells.
• This condition cannot be corrected but to
prevent the occurrence of this syndrome on
the patient's posterity, it is best that genetic
testing be completed.
• ~1 in every 1,000 males acquire the extra Y
chromosome.
The truth about XYY
Normal v. mutation
Normal v. mutation
• People normally have 46
chromosomes in each cell. Two
of the 46 chromosomes, known
as X and Y, are called sex
chromosomes because they help
determine whether a person will
develop male or female sex
characteristics. Females typically
have two X chromosomes
(46,XX), and males have one X
chromosome and one Y
chromosome (46,XY).
• 47,XYY syndrome is caused by
the presence of an extra copy of
the Y chromosome in each of a
male's cells. As a result of the
extra Y chromosome, each cell
has a total of 47 chromosomes
instead of the usual 46. It is
unclear why an extra copy of the
Y chromosome is associated
with tall stature, learning
problems, and other features in
some boys and men.
Mutation v. mutation
XYY
• Jacobs Syndrome is usually associated
with early growth development in young
adolescents, which results in taller
stature.
• Increased presence of acne has also been
associated with male individuals who
have the presence of an extra Y
chromosome.
• Decreased muscle tone and general
atrophy has been linked to Jacobs
Syndrome.
• No true indication of increased
masculinity with the exception of height.
XXY
• Klinefelter Syndrome is usually
associated with increased femininity
in males who have an extra X
chromosome.
• As infants, males have decreased
muscularity and strength; as adults,
reduced coordination and muscle
control are associated with this
chromosomal mutation.
• During puberty, decreased levels of
testosterone result in increased
femaleness.
Medications to ease symptoms
• How do treat Jacob’s Syndrome?
• Currently there is no cure for Jacob’s Syndrome, however scientists have developed therapy treatments to
help the affected person tolerate the disorder. Males with Jacob’s Syndrome can have explosive tempers.
There is often pain associated with Jacob’s
Syndrome
Learning difficulties are associated with
Jacob’s Syndrome
• Males with Jacob’s Syndrome
often have joint pain and painful
bone growth due to growing at
an accelerated rate.
• Pain killers and antiinflammatory medicines are
prescribed to ease the pain.
• In some cases support braces
are used to relieve joint pain.
• Males with Jacob’s Syndrome sometimes have
developmental learning problems. They may
require speech therapy, specialized learning
techniques and sometimes require special needs
consideration.
Dystrophic
Epidermolysis Bullosa
Background
-Discovered by Heinrich Koebner in 1886
-Broken down into subgroups in 1960s
-Specific causes discovered in 1980s/1990s
-Epidermis is the outer layer of skin
- “lysis” means breakdown
- “bullosa” means blister
About DEB
-Three subgroups, all genetic mutations
-Dominant and recessive
-Outlook depends on severity
What does it look like?
-Blisters can cover 75% of the body
-Thin skin, easily scars
-Malformed or missing fingernails
-Sometimes fused fingers/toes
What’s the Problem?
-Collagen VII
-protein that holds layers of skin together
-misshapen, reduced number, completely
missing
-coding gene on chromosome 3p21.1
Living with DEB
-Draining blisters
-Bandages
-Liquids and soft foods
-Loose fitting clothing
-Oral problems
-“Butterfly Children”
Discovery
• Turner Syndrome was discovered in 1938 by Dr. Henry Turner.
• In 1938, he also described and came up with the first treatment for
Turner Syndrome.
• He observed a set of common physical features in his patients, however
it wasn’t until 1960 when the chromosomal abnormality was found.
• Turner Syndrome occurs in 1 out of 2,500
newborn girls worldwide.
• Usually the fetus does not survive to term.
• Turner Syndrome affects 60,000 girls in the
United States.
CAUSES
• Most cases of Turner Syndrome are not inherited.
• Most females affected by Turner Syndrome suffer from monosomy X
which means that the female is missing the second X chromosome.
• Nondisjunction, which causes abnormal numbers of chromosomes in
reproductive cells, is usually the cause of Turner Syndrome.
←Karyotype
Symptoms of Turner
Syndrome