Chromosomal Aberrations.ppt

Copyright © 2009 Pearson Education, Inc.
SBB 1054 Genetics
Prepared by Pratheep Sandrasaigaran
Lecturer at Manipal International University
1

Lecturer at Manipal International University
5.0 Chromosomal
Aberrations
2

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

5.1 Introduction

• 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

Two- Chromosomal abnormalities
Adopted from Human Genetics
concepts and Application 9th ed.
• Abnormal Chromosome
Number
• Abnormal Chromosome
Structure

5.2 Abnormal Chromosome
Number

• 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

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

• 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).
a. Polyploidy

• 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 triploid or tetraploids in
human?
• Human liver, for example, has some
tetraploid (4N) and even octaploid (8N)
cells.
a. Polyploidy

http://www.jbc.org/content/278/21/19095.full.pdf+html

• 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.
b. Aneuploidy

• 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 1st or 2nd meiotic
division.
b. Aneuploidy- Trisomy

Adopted from Human Genetics concepts and Application 9th ed.
sperm or
oocyte

• 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.
b. Aneuploidy

• 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)
Chances of chromosome
abnormalities- rare

• 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

SBB 1054 Genetics_Q1.L5
19

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

5.2.1 Autosomal Aneuploidy

• 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

• 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

• 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%.
Adopted from Human Genetics concepts
and Application 9th ed.

• 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

b. Trisomy 18- Edward syndrome

• 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

c. Trisomy 13- Patau syndrome

• Hypothesis 1: Older a woman is susceptible for longer oocytes
arrested to complete meiosis (15 to 45 years) in the mean time
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

TEST YOUR KNOWLEDGE 1

Name the syndrome below.
• Trisomy 21
• Heart and kidney defects
• Hearing and vision loss.
• Digestive system
blockages are common
and may require surgical
correction.
Down syndrome

• Trisomy 13
• Fusion of the developing
eyes.
• There may be extra
fingers and toes.
Patau syndrome

• 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

6.2.2 Sex Chromosome
Aneuploidy

Syndromes

Sex Chromosome
Aneuploidy: Female

• 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
OR

• 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.

• Hormones (estrogen and progesterone) can be given
to stimulate development of secondary sexual
structures.
• Growth hormone can be prompt to maximize height.
• Susceptible to osteoporosis, types 1 and 2 diabetes,
and colon cancer.

• 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
OR

Sex Chromosome
Aneuploidy: Male

OR
• 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

OR
• 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

• 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

• 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
OR

• 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?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC202917
1/pdf/brmedj03403-0031.pdf

SBB 1054 Genetics_Q2.L5
50

1. What happens during meiosis to produce the increased risk of
trisomy 21 Down syndrome in the offspring 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?
Additional Questions

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.

5.3 Abnormal Chromosome
Structure

• Structural chromosomal defects:
• Missing genetic material
• Extra genetic material
• Inverted genetic material
• Combined or exchanged parts of non-
homologs (translocations)
Introduction

• 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

a. Deletions and Duplications
Chromosome 15
• Deletions and duplications can arise from chromosome rearrangements.
• These include translocations, inversions, and ring chromosomes

a. Disorders of Deletions and
Duplications
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.

Translocation
Robertsonian
translocation
Reciprocal
translocation

b. Translocation Down Syndrome
• 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.

A case study in Robertsonian
translocation
• 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.
Translocation
carrier

A Robertsonian translocation

b. Reciprocal translocation
• 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.

b. Reciprocal translocation
• 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
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

c. Inversions
• 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

d. Isochromosomes and Ring
Chromosomes
• 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.

d. Isochromosomes and Ring
Chromosomes
• 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

Summery of
Chromosomal
Aberrations

TEST YOUR KNOWLEDGE 2

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

Chromosomal Aberrations.ppt

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