Ch6 chromosomal aberrations

Presenting on the chromosomal aberration both in structure and number. Insight view in some disorders caused by chromosomal aberration including down syndrome, Patau syndrome, Edward syndrome and XY sex chromosome.

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6.0 Chromosomal Aberrations
Prepared by Pratheep Sandrasaigaran

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By the end of this chapter
you should be able to:
•Understand the meaning of Chromosomal
aberrations.
•Abnormalities in chromosome
•Numerical
•Structural
•Disorders
Prepared by Pratheep Sandrasaigaran
Diagram adopted from Internet Sources

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6.1 Introduction
Prepared by Pratheep Sandrasaigaran

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•What is meant by chromosomal abnormality?
•Additional of genetic material or whole
chromosome.
•Part of or a whole chromosome has been
missing.
•Defective formation of a chromosome.
•Increases or decreases in genetic material affect
the normal development and function.
Chromosomal abnormalities
Prepared by Pratheep Sandrasaigaran

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Prepared by Pratheep Sandrasaigaran
Two Chromosomal abnormalities
Adopted from Human Genetics
concepts and Application 9th ed.
•Abnormal Chromosome
Number
•Abnormal Chromosome
Structure

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6.2 Abnormal Chromosome
Number
Prepared by Pratheep Sandrasaigaran

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TECHNOLOGY
•What is the total chromosome found in your
cells?
•A human karyotype is said abnormal if the
number of chromosomes in a somatic cell is
not 46.
•Abnormal chromosomes account for at least
50% of spontaneous abortions.
•Yet only 0.65% of newborns have abnormal
chromosomes.
Abnormal Chromosome
Number
Prepared by Pratheep Sandrasaigaran

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Schematic presentation
Prepared by Pratheep Sandrasaigaran
Euploid
Autosomal Aneuploidy
Sex Chromosome Aneuploidy
Aneuploidy
Abnormal Chromosome
Number
Polyploidy
Triploid
Tetraploid
Octaploid
•Sex chromosome aneuploidy is less severe
than autosomal aneuploidy.

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•A cell with an entire extra sets of chromosomes.
•An individual whose cells have three copies of
each chromosome is a triploid 3N. How?
•Mostly result from fertilization of an oocyte by
two sperm, or.
•Diploid gamete (When a normal haploid sperm
fertilizes a diploid oocyte).
Polyploidy
Prepared by Pratheep Sandrasaigaran

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•Triploids account for 17 percent of
spontaneous abortions and 3 percent of
stillbirths and newborn deaths.
•Polyploids are very common among
flowering plants, including roses, cotton,
barley, wheat, and in some insects.
•Fish farmers raise triploid salmon, which
cannot breed.
•Can you see more then a triploid?
•The liver, for example, has some
tetraploid (4N) and even octaploid
(8N) cells.
Polyploidy
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics
concepts and Application 9th ed.

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•Cells missing a single chromosome or having an
extra one due to defective meiosis in a parent.
•Rarely, aneuploids can have more than one missing
or extra chromosome.
•Most autosomal aneuploids (with a missing or extra
non-sex chromosome) are spontaneously aborted
while Sex chromosome aneuploidy usually produces
milder symptoms.
•Those that survive have specific syndromes
depending upon which chromosomes in matter.
Aneuploidy
Prepared by Pratheep Sandrasaigaran

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•Children mostly born with extra chromosome
(trisomy) rather than a missing one (monosomy).
•Monosomies are so severe that an affected
embryo ceases developing.
•The meiotic error that causes aneuploidy is called
nondisjunction; chromosome pair fails to separate
at anaphase of either the 1
st
or 2
nd
meiotic division.
Aneuploidy- Trisomy
Prepared by Pratheep Sandrasaigaran

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Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics concepts and Application 9th ed.
sperm or
oocyte

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•What happens when such a gamete fuses with its
partner at fertilization?
•The zygotes will have either 45 or 47 chromosomes,
instead of the normal 46.
•Out of 49 possible aneuploidy, only nine types of
aneuploids are recognized in newborns.
Aneuploidy
Prepared by Pratheep Sandrasaigaran

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•Abnormal oocytes mostly have extra or missing
chromosomes.
•Abnormal sperm often have structural variants, such
as inversions or translocations.
•Most of the 50 percent of spontaneous abortions is
due to:
•Triploids
•Trisomy 16
•45,X individuals (missing an X chromosome)
•dac
Chances of chromosome
abnormalities- rare
Prepared by Pratheep Sandrasaigaran

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•About 9 percent of spontaneous abortions happen
due to:
•Trisomy 13
•Trisomy 18
•Trisomy 21
•More than 95 percent of newborns with abnormal
chromosome numbers have an extra or missing X or Y
chromosome.
•Chromosome abnormalities- all together make 0.1
percent of all children. But nondisjunction occurs in 5
percent of recognized pregnancies.
Chances of chromosome
abnormalities- rare
Prepared by Pratheep Sandrasaigaran

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TEST YOUR KNOWLEDGE 1
Prepared by Pratheep Sandrasaigaran

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1.Distinguish among a euploid, aneuploid,
and polyploid
2.What happens during meiosis to produce:
a.an aneuploid
b.Polyploid
Prepared by Pratheep Sandrasaigaran
Autosomal Aneuploidy
Sex Chromosome Aneuploidy
Aneuploidy
Abnormal Chromosome
Number
Polyploidy
Triploid
Tetraploid
Octaploid

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6.2.1 Autosomal Aneuploidy
Prepared by Pratheep Sandrasaigaran

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•Chromosomes 21, 18, and
13….Why?
•These chromosomes carry
far fewer protein-
encoding genes than the
other autosomes,
compared to their total
amount of DNA.
•Therefore, extra copies of
these chromosomes are
tolerated.
Common Trisomies
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics concepts and Application 9th ed.

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•Most common autosomal aneuploidy.
•Many people with Down syndrome have physical
problems:
•Heart and kidney defects
•Hearing and vision loss.
•A suppressed immune system can make influenza
deadly.
•Digestive system blockages are common and may
require surgical correction
a. Trisomy 21- Down syndrome
Prepared by Pratheep Sandrasaigaran

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•Chances of Trisomy 21 Down syndrome
increases with the age of the mother.
•About 90 percent of trisomy 21
conceptions are due to nondisjunction
during meiosis I in the female.
•The 10 percent of cases due to the male
result from nondisjunction during meiosis
I or II.
•The chance that trisomy 21 will recur in a
family is 1%.
a. Trisomy 21- Down syndrome
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics concepts
and Application 9th ed.

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•Edward syndrome have great physical and mental
disabilities, with developmental skills usually
stalled at the 6-month level.
•Major abnormalities include heart defects, a
displaced liver, growth retardation, and oddly
clenched fists, abnormally shaped and low-set
ears, a small mouth and face, unusual or absent
fingerprints.
•Most cases of trisomy 18 are traced to
nondisjunction in meiosis II of the oocyte.
b. Trisomy 18- Edward
syndrome
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics
concepts and Application 9th ed.

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•About 92 percent of infants born with an extra
chromosome 13 do not live to see their first
birthdays
•Most striking is a fusion of the developing eyes, so
that a fetus has one large eyelike structure in the
center of the face.
•Major abnormalities affect the heart, kidneys, brain,
face, and limbs. The nose is often malformed, and
cleft lip and/or palate is present in a small head.
•There may be extra fingers and toes.
c. Trisomy 13- Patau syndrome
Prepared by Pratheep Sandrasaigaran

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•Hypothesis 1: Older a woman is susceptible for
longer oocytes arrested to complete meiosis (15 to
45 years) due to exposure to toxins, viruses, and
radiation.
•Hypothesis 2: Females have a pool of immature
aneuploid oocytes resulting from spindle
abnormalities that cause nondisjunction. The
abnormal oocytes remain to be released at later age.
•Hypothesis 3: Trisomies result from gametes in
which a homolog pair do not extensively cross over
during meiosis I and suppose to migrate to the same
pole, packaging an extra chromosome into a gamete.
Why trisomy at late pregnancy
Prepared by Pratheep Sandrasaigaran

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TEST YOUR KNOWLEDGE 2
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Name the syndrome below.
Prepared by Pratheep Sandrasaigaran
•Trisomy 21
•Heart and kidney defects
•Hearing and vision loss.
•Digestive system
blockages are common
and may require surgical
correction.
Down syndrome
Diagram adopted from Internet Sources

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Name the syndrome below.
Prepared by Pratheep Sandrasaigaran
•Trisomy 13
•Fusion of the developing
eyes.
•There may be extra
fingers and toes.
Patau syndrome
Diagram adopted from Internet Sources

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Name the syndrome below.
Prepared by Pratheep Sandrasaigaran
•Trisomy 18
•Most cases of trisomy 18
are traced to
nondisjunction in meiosis
II of the oocyte
•Oddly clenched fists,
abnormally shaped and
low-set ears, a small
mouth and face.
Edward syndrome
Diagram adopted from Internet Sources

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6.2.2 Sex Chromosome
Aneuploidy
Prepared by Pratheep Sandrasaigaran

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Adopted from Human Genetics
concepts and Application 9th ed.
Prepared by Pratheep Sandrasaigaran
Syndromes

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Prepared by Pratheep Sandrasaigaran
Sex Chromosome
Aneuploidy: Female
Diagram adopted from Internet Sources

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•By 1959, karyotyping confirmed the presence of
only one X chromosome.
•At birth, a girl with XO syndrome looks normal,
except for puffy hands and feet caused by impaired
lymph flow.
•Some with XO syndrome have impaired hearing and
frequent ear infections due to a small defect in the
coiled part of the inner ear.
•They cannot hear certain frequencies of sound.
a. XO Syndrome- Turner
Prepared by Pratheep Sandrasaigaran

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•At sexual maturity, thin body hair develops, but the
girls do not ovulate or menstruate, and their breasts
do not develop.
•The uterus is very small, but the vagina and cervix
are normal size.
•In the ovaries, oocytes speed through development,
depleting the supply during beginning of
menstruation.
a. XO Syndrome- Turner
Prepared by Pratheep Sandrasaigaran

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•Hormones (estrogen and progesterone) can be given
to stimulate development of secondary sexual
structures.
•Growth hormone can be prompt to maximize height.
•Individuals who are mosaics* may have children, but
their offspring are at high risk of having abnormal
numbers of chromosomes.
•Susceptible to osteoporosis, types 1 and 2 diabetes,
and colon cancer.
a. XO Syndrome- Turner
Prepared by Pratheep Sandrasaigaran

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•Having an extra X chromosome in each of her
cells.
•The only symptoms are tall stature and
menstrual irregularities.
•less intelligent than their siblings but rarely
retarded.
b. Triplo-X
Prepared by Pratheep Sandrasaigaran

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Prepared by Pratheep Sandrasaigaran
Sex Chromosome
Aneuploidy: Male
Diagram adopted from Internet Sources

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•Severely affected men are underdeveloped sexually,
with immature testes and prostate glands
•Having sparse pubic and facial hair and they are
slow learners.
•They have very long arms and legs, large hands and
feet, and may develop breast tissue.
•Testosterone injections during adolescence can
limit limb lengthening and stimulate development
of secondary sexual characteristics.
a. XXY Syndrome- Klinefelter
Prepared by Pratheep Sandrasaigaran

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•A male with an extra X chromosome and an extra Y
chromosome.
•Tend to develop foot and leg ulcers, resulting from
poor venous circulation.
•Childhood and adolescence often include attention
deficit disorder, obsessive compulsive disorder, and
learning disabilities.
•In the teen years, testosterone level is low,
development of secondary sexual characteristics is
delayed, and the testes are undescended
b. XXYY Syndrome
Prepared by Pratheep Sandrasaigaran

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•XXYY Syndrome and Klinefelter are hard to be
distinguih.
•XXYY Syndrome share many characteristics
Klinefelter , however XXYY Syndrome have more
severe behavioral problems.
•Klinefelter can fathered children, with medical
assistance where else man with XXYY syndrome is
infertile.
Klinefelter vs XXYY Syndrome
Prepared by Pratheep Sandrasaigaran

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•96% of XYY males are apparently normal.
•Symptoms attributable to the extra chromosome
may be great height, acne, and perhaps speech
and reading problems.
•Prevalence of XYY are more psychological than
biological.
c. XYY Syndrome- Jacobs syndrome
Prepared by Pratheep Sandrasaigaran

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•Geneticists have never observed a sex
chromosome constitution of one Y and no X.
•Y chromosome carries little genetic material.
•The absence of X chromosome which having
more gene would not support the development
of YO embryo beyond a few cell divisions.
Why no sex chromosome
constituted of Y alone?
Prepared by Pratheep Sandrasaigaran

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TEST YOUR KNOWLEDGE 3
Prepared by Pratheep Sandrasaigaran

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1.What happens during meiosis to produce the
increased risk of trisomy 21 Down syndrome in the
off spring of a woman over age 40 at the time of
conception?
2.Describe an individual with each of the following
chromosome constitutions. Mention the person’s
sex and possible phenotype.
a.47,XXX
b.45,X
c.47,XX, trisomy 21
3.How many chromosomes would a person have who
has Klinefelter syndrome and also trisomy 21?
Prepared by Pratheep Sandrasaigaran

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4.Explain why a female cannot have XXY syndrome
and a male cannot have XO syndrome.
5.A couple has a son diagnosed with XXY syndrome.
Explain how the son’s chromosome constitution
could have arisen from either parent.
6.Distinguish among Down syndrome caused by
aneuploidy and mosaicism.
7.Which chromosomal anomaly might you expect to
find more frequently among the members of the
National Basketball Association than in the general
population? Cite a reason for your answer.
Prepared by Pratheep Sandrasaigaran

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6.3 Abnormal Chromosome
Structure
Prepared by Pratheep Sandrasaigaran

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•Structural chromosomal defects:
•Missing genetic material
•Extra genetic material
•Inverted genetic material
•Combined or exchanged parts of non-
homologs (translocations)
Introduction
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics
concepts and Application 9th ed.

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•Deletions (missing) and duplications (extra)
DNA sequences.
•More genes involved, the more severe the
associated syndrome.
•Small duplications do not affect the
phenotype, but larger ones may.
•Often arise “ de novo, ” which means that
neither parent has the abnormality, and it is
therefore new.
a. Deletions and Duplications
Prepared by Pratheep Sandrasaigaran

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a. Deletions and Duplications
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics
concepts and Application 9th ed.Chromosome 15
•Deletions and duplications can arise from chromosome rearrangements.
•These include translocations, inversions, and ring chromosomes

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a. Disorders of Deletions and
Duplications
Prepared by Pratheep Sandrasaigaran
1.A young boy who had difficulty concentrating and
sleeping and would often scream for no reason had a
small duplication in chromosome 7.
2.A young girl plagued with head-banging behavior,
digestive difficulties, severe constipation, and great
sensitivity to sound had a microdeletion in
chromosome 16.
3.Ashley Elizabeth Naylor had a cri-du chat (cat cry)
syndrome aka 5p− syndrome where part of the p arm
of one copy of chromosome 5 is missing; intellectual
disability and developmental delay.

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Translocation
Prepared by Pratheep Sandrasaigaran
Robertsonian
translocation
Reciprocal
translocation

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b. Translocation Down Syndrome
Prepared by Pratheep Sandrasaigaran
•In a translocation, different (non-homologous)
chromosomes exchange or combine parts.
•A translocation can affect the phenotype if it
breaks a gene or leads to duplications or
deletions in the chromosomes of offspring.
•In 1 in 20 cases of Down syndrome, a parent has a
Robertsonian translocation between
chromosome 21 and another, usually
chromosome 14.

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A case study in Robertsonian
translocation
Prepared by Pratheep Sandrasaigaran
•The short arms of two different acrocentric
chromosomes break.
•leaving sticky ends on the two long arms that join,
forming a single, large chromosome with two long
arms (chromosome 14/21).
•The tiny short arms are lost, but their DNA
sequences are repeated elsewhere in the genome,
so the loss does not cause symptoms; having 45
chromosomes.
•Even so, he or she may produce unbalanced
gametes.
Adopted from Human Genetics
concepts and Application 9th ed.
Translocation
carrier

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Prepared by Pratheep Sandrasaigaran
A Robertsonian translocation
Adopted from Human Genetics concepts and Application 9th ed.

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b. Reciprocal translocation
Prepared by Pratheep Sandrasaigaran
•In a reciprocal translocation, two non-homologous
chromosomes exchange parts.
•genes C, D, and E on the blue chromosome exchange
positions with genes M and N on the red
chromosome.
Adopted from Human Genetics
concepts and Application 9th ed.

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b. Reciprocal translocation
Prepared by Pratheep Sandrasaigaran
•If the chromosome exchange does not
break any genes, the person is healthy
and a translocation carrier.
•He or she has the normal amount of
genetic material, but it is rearranged.
•FISH can be used to highlight the
involved chromosomes
Adopted from Human Genetics
concepts and Application 9th ed.The pink chromosome with the dab of
blue, and the blue chromosome with a
small section of pink, are the
translocated chromosomes
Fluorescence in situ hybridization

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c. Inversions
Prepared by Pratheep Sandrasaigaran
•An inverted sequence of chromosome bands
which disrupts important genes effects, in only 5
to 10 percent of cases.
•If neither parent has the inversion, then it may
arose in a gamete
•Two types of inversions are distinguished by the
position of the centromere relative to the
inverted section:
•Paracentric inversion
•Pericentric inversion

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i. Paracentric inversion
Prepared by Pratheep Sandrasaigaran
•Four different outcomes are to be
seen if a crossover occurs with the
normal homolog:
•One normal chromatid (1)
•One inverted chromatid (3)
•One with two centromeres
(dicentric)(2)
•One with no centromere (an
acentric fragment)(4)
•A paracentric inversion does not
include the centromere in the
loop.
Adopted from Human Genetics concepts and
Application 9th ed.

59. Copyright © 2009 Pearson Education, Inc.
Adopted from Human Genetics concepts and
Application 9th ed.
i. Paracentric inversion
Prepared by Pratheep Sandrasaigaran
•In dicentric two centromeres are
pulled to opposite sides of the
cell, and the chromosome
breaks, leaving pieces with extra
or missing segments when the
cell divides.
•In acentric fragment When the
cell divides, the fragment is lost
because a centromere is
required for cell division

60. Copyright © 2009 Pearson Education, Inc.
Adopted from Human Genetics concepts and
Application 9th ed.
ii. Pericentric inversion
Prepared by Pratheep Sandrasaigaran
•A pericentric inversion includes the
centromere within the loop.
•A crossover of homologous produces
two chromosomes that have
duplications and deletions, but one
centromere each.

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d. Isochromosomes and Ring
Chromosomes
Prepared by Pratheep Sandrasaigaran
•A chromosome that has identical arms due
to the centromeres part in the wrong plane.
•Isochromosomes are known for
chromosomes 12 and 21 and for the long
arms of the X and the Y.
Adopted from Human Genetics
concepts and Application 9th ed.

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d. Isochromosomes and Ring
Chromosomes
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics
concepts and Application 9th ed.
•Ring chromosomes may arise when
telomeres are lost, leaving sticky ends
that adhere.
•Most ring chromosomes consist of DNA
repeats and do not affect health,
however some do.
•6-year-old Cara Ford lost the ability to
walk, talk, or eat and developed seizures
in the event of ring chromosome 20

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Summery of
Chromosomal
Aberrations
Prepared by Pratheep Sandrasaigaran
Adopted from Human Genetics concepts and Application 9th ed.

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TEST YOUR KNOWLEDGE 4
Prepared by Pratheep Sandrasaigaran

65. Copyright © 2009 Pearson Education, Inc.
Prepared by Pratheep Sandrasaigaran
1.For an exercise in a college genetics laboratory course, a
healthy student constructs a karyotype from a cell from the
inside of her cheek. She finds only one chromosome 3 and
one chromosome 21, plus two unusual chromosomes that do
not seem to have matching partners.
a.What type of chromosomal abnormality does she have?
b.Why doesn’t she have any symptoms?
2.List three examples illustrating the idea that the amount of
genetic material involved in a chromosomal aberration affects
the severity of the associated phenotype.
3.Define or describe the following technologies:
a.FISH
b.Amniocentesis