Chapter 6.
1 - CHROMOSOMES
What is a Chromosome?
● Highly condensed form of DNA
● Wrapped into nucleosomes
● Wrapped into chromatin fiber
● Condensed during metaphase into the familiar
shape
● Humans have 22 pairs of autosomal chromosomes
and one pair of sex chromosomes
● Are rod-shaped, filamentous bodies present in the
nucleus, which become visible during cell division.
● They are the carriers of the gene or unit of heredity.
● Are not visible in the active nucleus due to their high
water content but are clearly seen during cell
division.
● Were first described by Strausberger in 1875.
● The term “Chromosome” was first used by
Waldeyer in 1888.
The term Chromosome is derived from:
➢ Chromo = color
➢ Soma = body
Number of chromosomes:
● Normally, all the individuals of a species have the
same number of chromosomes.
● Euploidy - the presence of a whole set of
chromosomes is called.
● Aneuploidy - a change in the chromosome number
that does not involve entire sets of chromosomes
but only a few of the chromosomes.
● Haploid - gametes normally contain one set of
chromosomes.
● Somatic cells - usually contain two sets of
chromosomes.
○ 2n - Diploid
○ 3n - triploid
○ 4n - tetraploid
Chromosome Size:
In contrast to other cell organelles, the size of
chromosomes shows a remarkable variation depending upon
the stages of cell division.
● Interphase: chromosomes are longest & thinnest.
● Prophase: there is a progressive decrease in their
length accompanied by an increase in thickness.
● Anaphase: chromosomes are small.
● Metaphase: chromosomes are the most easily
observed and studied during metaphase when they
are very thick, quite short, and well spread in the
cell.
➔ Chromosomes can be distinguished by “painting” -
using DNA hybridization + fluorescent probes
Types of Chromosomes:
● Autosomes:
○ Paired chromosomes with/ the same
length, shape, centromere location, and
genes.
○ Any chromosomes other than a sex
chromosome
○ Determine the size, color, & hair of a body.
● Sex chromosomes:
○ Members of a pair of chromosomes that
differ between males and females.
 Chromosome Types:
There are four types of chromosomes, and
it is classified based on the position of the
centromere

1. Telocentric - no p arm; centromere is on

the end part.
2. Acrocentric - has very small p arm;
centromere is very near the end part.
3. Submetacentric - p arm is just a little
smaller than the q arm; the centromere is
in the middle part.
4. Metacentric - p and q arms are exactly the
same length; the centromere is in the
exact middle part of the chromosome.

Things to remember:
➔ Homologous chromosomes are
● p arm - the smaller of the two arms (p - stands for ◆ not genetically identical.
petite) ◆ They can have different alleles of genes.
● q arm - the longer of the two arms ➔ Sister chromatids are:
➔ Bands are numbered from centromere outward ◆ Genetically identical.
◆ Forms as cells go through the S phase
(replication).
◆ Attached to each other by centromere until
anaphase of Mitosis.
◆ Once separated, each is again referred to
as a chromosome.

● Cytogenetics:
○ Study of chromosomes and chromosomal
abnormalities
 ○ Study Karyotypes - picture of an ● Translocations:
individual’s chromosomes in Metaphase, ○ Non-homologous chromosomes have
spread out on a slide. exchanged pieces (cross over)
■ Robertsonian Translocation
Human Chromosomal Abnormalities: ● Two q arms of two
different chromosomes
● Numerical Chromosomal Aberrations: come together.
○ Trisomy = 3 copies of single chromosome ● Two p arms are lost
(47) entirely.
○ Monosomy = 1 copy of a single
chromosome (45)
○ Triploidy = 3N
○ Tetraploidy + 4N
● Structural Chromosomal Aberrations
○ Deletion
○ Duplication
○ Translocation (involves 2 chromosomes)
○ Inversion
○ Isochromosome
○ Ring Chromosome

Abnormal Number:
■ Reciprocal Translocation
➢ Polyploidy: complete extra set of chromosomes ● Two different
○ Three of every chromosomes chromosomes exchange
○ Cannot survive to birth parts.
➢ Aneuploidy: missing or extra of one chromosome ● Since all parts are still
○ Monosomy - missing one chromosome present, it is often
○ Trisomy - one extra chromosome normal.
○ Only Trisomy 13, 18, and 21 are viable

Uniparental Disomy:
➔ When nondisjunction occurs in both the mother and
the father’s gametes causing two copies of one
chromosome to come only from one parent.
➔ “Two bodies, one parent” - bodies are
chromosomes
➔ Incredibly rare event
➔ More often, nondisjunction leads to either
monosomy or trisomy.
➔ Haplotype refers to a set of DNA variants along a
single chromosome that tend to be inherited
together. ● Inversions:
○ One part of the chromosome has been
flipped around in the opposite direction.

○ Again, individual may be normal

○ Unless inversion breakpoints are in middle
of a gene
○ Or unless inversion affects centromeres

Abnormal Structure:

● Deletion:
○ Large part of one chromosome has been
lost during mitosis.
○ Vary in size - larger is more severe
● Duplication:
○ Large part of one chromosome has been
duplicated on the same chromosome
○ Vary in size - larger is more severe
● Isochromosomes:
○ Have two identical arms
○ Two p’s or two q’s and not the other
● Ring chromosome:
○ Telomeres are lost, or don’t function
○ So one end of chromosome attaches to
another end forming a ring
○ Cannot undergo mitosis successfully
 ➔ Causes of Chromosomal Disorders:
◆ Ionising radiation, autoimmunity, virus,
infections and chemical toxins in the
pathogenesis of certain disorders.
● Non-disjunction:
○ Unequal division of chromosomes during
Meisos
○ Can happen to either sperm or oocyte
○ From one gamete w/ two copies of same
chromosome
○ Other gamete with zero copies of that
chromosome
○ Different outcomes if happens at first or
second stage of Meiosis.
Numerical Chromosomal Aberrations
● XXY or Klinefelter’s syndrome (Male)
○ Feminine character
○ Tall, Normal Intelligence
● XYY or Jacob’s syndrome (Male)
○ Height, more active
○ Slight learning disability
○ Normal intelligence
● XXX = Trisomy X Female
○ Produce healthy female
● X/XO = Turner syndrome (Female)
○ Webbed neck
○ Short height
○ Immature females
● Patau’s Syndrome (#13 Trisomy)
○ Small heand, small or missing eyes
○ Heart defects, Extra fingers
○ Abnormal genitalia
○ Mentally retarded
○ Cleft palate
○ Most die a few weeks after birth
● Trisomy 21 or Down Syndrome
○ Characteristic facial apperance
■ Small nose, flat face, epicanthal
fold.
○ SIngle palmar crease
○ Mental retardation (avg. IQ <50)
○ Multiple complications
■ Heart disease
■ Leukemia
■ Epilepsy
○ Some fertility problems
● Trisomy 18 or Edwards Syndrome:
○ 1/8000 live births; maternal age affect
○ Low birth weight
○ Multiple dysmorphic features
■ Chin, ears, single palmar crease,
clenched hands
○ Malformation of the brain, heart, kidneys,
and other organs
○ Rarely survive beyond 1 year
Chapter 6.2 - KARYOTYPING
What is karyotyping?
➔ Karyotyping is one of the techniques that allows us
to diagnose several thousand possible genetic
diseases in humans.
➔ It also refers to the use of a microscope to examine
the size, shape, and number of chromosomes in a
sample of body cells.
➔ Extra, missing, or abnormal positions of
chromosome pieces can cause problems with a
person’s growth, development, and body function.
What is a karyotype?
➔ The number and visual appearance of the
chromosomes in the nucleus of a cell is called a
karyotype.
➔ Remember that one chromosome of each pair
comes from the other and the other from the father.
Thus, each parent contributes 23 chromosomes.
When is chromosome analysis indicated?
➔ Chromosome analysis - is recommended as a
routine diagnostic procedure for a number of
indications, including (but not limited to) the
following:
1. Problems noted during early growth or
development: Failure to thrive, developmental
delay, dysmorphic (unusual) feature, multiple birth
defects, short stature, ambiguous genitalia, and
mental retardation are frequent findings amongst
individuals w/ chromosome abnormalities, although
they are not exclusive to this group.
2. Stillbirths and neonatal deaths: The incidence of
chromosome abnormalities is much higher amongst
stillbirths and infants who die shortly after birth
(each about 10%) than among live births (0.7%).
Chromosome analysis may be able to identify a
cause for the loss and provide important information
for prenatal diagnosis in future pregnancies for
parents.
3. Fertility problems: Chromosome analysis is
recommended for women who are past the typical
age of puberty and have never had a menstrual
cycle as well as couples with a history of infertility or
recurrent miscarriage. Chromosome abnormalities
can be seen in one or the other parent in
approximately 3-6% of infertility or recurrent
miscarriage cases.
4. Pregnancy in women 35 years or older at the
time of delivery: Though anyone at any age has a
chance to have a child with/ a chromosome
abnormality, the chances of increase with
increasing maternal age. Chromosome analysis of
the fetus should be offered as a routine part of
prenatal care in such pregnancies.
5. Family history: A known or suspected
chromosome abnormality in a relative can be an
indication for chromosome analysis under some
circumstances.
Two categories of chromosome abnormalities:
1. Numerical - Chromosome abnormality simply
means that a person has a total number of
chromosomes different from 46, usually 47 or
sometimes 45 chromosomes, in each cell of their
body, respectively. Health problems and birth
defects are usually present as a result of having
extra or missing genetic material. An example of a
numerical chromosome abnormality is Down
syndrome, typically caused by having an entire
extra chromosome 21, for a total of three copies of
chromosome 21 instead of two.
2. Structural - This means that a portion of the
genetic material has been altered or rearranged in
some way; for example, a piece of one
chromosome may be attached to another
chromosome (translocation or a piece of a
chromosome may be turned upside down
(inversion).
Cells Used for Chromosomal Analysis:
● Any cell with a nucleus
● Lymphocytes
● Skin cells
● Tumor cells
● Amniotic cells
● Chorionic villi
● Rare fetal cells from maternal blood
➢ Amniocentesis:
○ Collects fetal cells for chromosomal and
biochemical studies.
○ Generally performed in the 16th week.
 analysis system for karyotyping (High-resolution images w/
12-bit digital CCD-camera (1280x1024 pixels).

Seven groups of chromosomes:

Group A - chromosomes 1-3 are largest w/ median

centromere.

Group B - chromosomes 4-5 are large with submedian

➢ Chorionic Villus Sampling:
centromere.
○ Somewhat risky for mother and fetus.
Group C - chromosomes 6-12 are medium-sized w/
submedian centromere.

Group D - chromosomes 13-15 are medium-sized w/

acrocentric centromere.

Group E - chromosomes 16-18 are short w/ median or

submedian centromere.

Group F - chromosomes 19-20 are short w/ median

centromere.

Group G - chromosomes 21-22 are very short w/acrocentric

centromere.

Chromosome X - similar to group C.

Chromosome Y - similar to group G.

➔ Chromosomes are arranged into seven groups

based on size and centromere location. The
centromeres can be found in the middle of the
chromosome (median), near one end (acrocentric),
or in between these first two (submedian).

KARYOTYPING
➔ Karyotype Analysis:
1 - Obtain a set of chromosomes.

2 - Match the chromosomes with/ their homologous mate.

One chromosome of each pair is numbered; as you match
your chromosomes, number the homologous pairs. You need
to be very systematic. The number one chromosome is the
largest. Its corresponding mate should be of the same size,
with the same banding pattern, and have the same
centromere location.

3 - Determine the karyotype abnormality using the

Chromosome Analysis.

4 - Research your abnormality using the resources available.

A photograph of a real karyotype for the disorder is in the
computer database; for example, Band ViewR is Applied
Spectral Imaging’s fully automated image acquisition and
Spectral Karyotyping (SKY)

Spectral Karyotyping:

➔ Refers to the application of spectral imaging to the

simultaneous visualization of all human (or other
species) chromosomes in different colors.
➔ A laboratory technique that allows scientists to
visualize all of the human chromosomes at one time
by “painting” each pair of chromosomes in a
different fluorescent color.

Principles of SKY:

➔ Uses fluorescent “tags” specific to each

chromosome
➔ Combining two techniques, in q996, the SKY
technique was developed by Schrock et al.

1. Chromosome painting: is a technique of

drawing an entire image of a certain
chromosome by using fluorescent signals.
2. Multicolor fluorescence: a technique of
drawing images of several hybridization
signals with different fluorescent dyes.
 human chromosomes at one time by “painting” each
pair of chromosomes in different fluorescent colors.

➢ Traditional karyotyping allows scientists to view the

full set of human chromosomes in black and white,
a technique that is useful for observing the number,
size, and shape of the chromosomes. Interpreting
these karyotypes, however, requires an expert, who
might need hours to examine a single chromosome.
By using SKY, even non-experts can easily see
instances where a chromosome, painted in one
color, has a small piece of a different chromosome,
painted in another color attached to it.

➢ Chromosomal Analysis can be useful in a wide

variety of clinical situations.
○ To detect chromosomal disorders in the
fetus
○ To reveal the cause of infertility or
repeated miscarriages.
○ To evaluate couples with chromosomally
abnormal children.
○ To evaluate women who are not
menstruating.
○ To examine abnormal sexual development,
particularly when there is doubt about true
gender.
○ To evaluate the course and the
effectiveness of treatment of certain
cancers.
○ To look for the cause of birth defects,
mental retardation, or retarded growth.
Advantages of SKY:

● Easy visual interpretation when analyzing results.

The result is a digital image rather than film, in full
color.
● Pairing of the chromosomes is simpler because
homologous pairs are the same color, and
aberrations and cross-overs are more easily
recognized.
● Used to detect translocations not recognized by
traditional banding analysis. When a chromosome
in which the origin cannot be identified or the
structural abnormality of a partial copy of a
chromosome is observed with G-banding, the SKY
technique makes it possible to recognize each
chromosome with different color tones.

SUMMARY:

➢ Karyotyping is a test to examine chromosomes in a

sample cell, which can help identify genetic
problems as the cause of a disorder or disease.
Also called Chromosome Analysis.

➢ The test can be performed on a sample of blood,

bone marrow, amniotic fluid, or tissue from the
placenta, and the organ that develops during
pregnancy to feed a growing baby.

➢ Spectral Karyotyping (SKY) is a laboratory

technique that allows scientists to visualize all of the