Robertsonian Translocation

45,XX,rob(13,14)
A Robertsonian translocation of chromosomes 13 and 14, an end to end fusion
of the two chromosomes, is seen here in a balanced rearrangement. There is
no net gain or loss of genetic material in this person so they would have a
normal phenotype. Their risk, however, for an abnormal child or spontaneous
pregnancy loss is increased.

Trisomy 21

47,XX,+21)
An extra chromosome 21 is the classic chromosomal constitution of individuals
with Down Syndrome. Partial trisomies of chromosome 21 and mosaicism has
also been observed associated with Down Syndrome.
Klinefelter's Syndrome

49,XXXXY
This karyotype shows a variant of Klinefelter's syndrome. Individuals with this
syndrome are male, typically with the karyotype 47,XXY. They exhibit a
characteristic phenotype including tall stature,
infertility, gynecomastia and hypogonadism. Aneuploidy above one extra
chromosome is usually fatal but because of X-inactivation, which "turns off" all
but one X chromosome per cell, the effects of 3 extra chromosomes are
reduced.

DiGeorge Syndrome
Individuals with the DiGeorge syndrome often have cardiac defects, immune
system deficiencies and can be moderately retarded. The cause of the
DiGeorge syndrome is a defect in chromosome 22, where one of the bands in
the long arm has been deleted. The deletion can be suspected by looking at
the karyotype and can be confirmed by FISH.

This image shows the karytype of an individual with the

DiGeorge syndrome. By looking carefully at the pair of 22's,
you can see that there is a light band missing in the
chromosome to the right. It might be easier to see the defect in
the composite karyotype of chromosome 22 from the same
individual.
This image shows a FISH, where the probe has been used to
locate the defect associated with the Digeorge syndrome.

XYY

47,XYY
This image shows the karyotype of a human male with an extra Y
chromosome. The abnormality has a variable phenotype that can include tall
stature and acne.

Philadelphia Chromosome

46,XX,t(9,22)
The classic rearrangement seen in about 90% of patients with Chronic
myelogenous leukemia(CML). It was originally thought to be a shortened 22
chromosome and dubbed the Philadelphia chromosome after the city in which
it was discovered. Later determined to be a translocation between
chromosomes 9 and 22 (part of 22 is attached to 9).

Inversion

Inversion

46,XY,inv(16)
This image shows an inversion of chromosome 16. By looking carefully att the
pair of 16, you will see that the chromosome on the right looks different from
the one on the left. The left one is normal and the right one is inverted near the
centromere.

Inversions, by definition, do not involve loss or gain of chromosomal material. If

the breakpoints of the inversion do not disrupt genes they may not have an
associated phenotype.

Banding Patterns

Chromosomes in metaphase can be identified using certain staining techniques, so called banding.
Cells are cultured and then stopped in metaphase to maximize the number of suitable cells. They
are then spread on a slide, stained with a suitable dye and visualized in the microscope. Most
conventional cytogenetic analyses depend on the karyotyping of banded metaphase
chromosomes.

A band is defined as that part of a chromosome which is clearly distinguishable from its adjacent
segments by appearing darker or brighter with one or more banding techniques. The chromosomes
are visualized as consisting of a continuous series of bright and dark bands.

The banding techniques fall into two principal groups: 1) those resulting in bands distributed along
the length of the whole chromosome, such as G-, Q- and R-bands and 2) those that stain a
restricted number of specific bands or structures. These latter include methods which
reveal centromeric bands, C-bands, and nucleolus organizer regions, NOR's (at terminal regions
of acrocentric chromosomes). C-banding methods do not permit identification of every
chromosome in the somatic cell complement, but can be used to identify specific chromosomes.

G- and R- bands can be bright field or fluorescent.

Bright field G-bands

These G-bands are most commonly used. They take their name from the Giemsa dye, but can be
produced with other dyes. In G-bands, the dark regions tend to be heterochromatic, late-replicating
and AT rich. The bright regions tend to be euchromatic, early-replicating and GC rich.

Bright field R-bands

These R-bands are approximately the reverse of G-bands (the R stands for "reverse"). The dark
regions are euchromatic and the bright regions are heterochromatic.

Fluorescent G- and R-bands

These bands are the photographic negative of the bright field versions. i.e. the reverse of the bright
field G-bands and R-bands.

Q-bands are like fluorescent G-bands, but certain heterochromatic regions are more brightly
stained with Q-banding.

Fluorescence In-Situ Hybridization (FISH)

Fluorescence In-Situ Hybridization is a method used to identify specific parts of a chromosome. For
example, if you know the sequence of a certain gene, but you don't know on which chromosome the
gene is located, you can use FISH to identify the chromosome in question and the exact location of
the gene. Or, if you suspect that there has been a translocation in a chromosome, you can use a
probe that spans the site of breakage/translocation. If there has been no translocation at that point,
you will se one signal, since the probe hybridizes to one place on the chromosome. If, however,
there has been a translocation, you will see two signals, since the probe can hybridize to both ends
of the translocation point.

To use FISH efficiently, you have to know what you're looking for, i.e. you usually suspect a
particular defect, based on the appearance of certain chromosomes, etc.

Here's how it works:

 Make a probe complementary to the known sequence. When making the probe, label it
with a fluorescent marker, e.g. fluorescein, by incorporating nucleotides that have the
marker attached to them.
 Put the chromosomes on a microscope slide and denature them.
 Denature the probe and add it to the microscope slide, letting the probe hybridize to its
complementary site.
 Wash off the excess probe and look at the chromosomes in a fluorescence microscope.
The probe will show as one or more fluorescent signals in the microscope, depending on
how many sites it can hybridize to.

Examples of Fluorescence In-Situ Hybridization

This image shows chromosomes with fluorescent R-bands.

The image has been pseudocolored, to look like it does in the
microscope. Otherwise, the imaging system turns out black
and white chromosomes. The bright green dots are probes
complementary to olfactory receptor homologues. In most
chromosomes these areas are subtelomeric, i.e. near the end
of the chromosomes, but in chromosome 2 (bottom, left) we
see that the probe has hybridized to the middle of the
chromosome. A comparison with ape chromosomes shows
that the human chromosome 2 is the result of an end to end
fusion of two ancestral chromosomes. As a result the two
subtelomeric ends became the middle of chromosome 2,
which is why we get hybridization of the probe there.

(Image contributed by Cynthia Friedman and Barbara Trask,

UW Department of Molecular Biotechnology)

(Image contributed by Cynthia Friedman and Barbara Trask,

UW Department of Molecular Biotechnology)

This image shows a probe for the Xist gene, on the X

chromosome.

This image shows a paint of chromosome 22. In addition to

the two normal copies of 22, there is also a small extra piece,
a marker, derived from 22 material
46,XY,inv(16)
This image shows an inversion of chromosome 16. By looking carefully att the pair of 16, you will
see that the chromosome on the right looks different from the one on the left. The left one is normal
and the right one is inverted near the centromere.

Inversions, by definition, do not involve loss or gain of chromosomal material. If the breakpoints of
the inversion do not disrupt genes they may not have an associated phenotype.

Back to Aquired Cytogenetic Abnormalities

Cytogenetic Nomenclature
Abbreviation

Meaning

Example

Condition

46, XXNormal Female Karyotype46, XYNormal Male

Karyotypecencentromeredeldeletion46,XX,del(5p)Female with

cri du chat syndrome due to deletion of part of short arm of one

chromosome 5derderivative chromosomeder(1)Translocation

chromosome derived from chromosome 1 and containing the

centromere of chromosome 1dicdicentric

chromosomedic(X;Y)Translocation chromosome containing

centromeres from both the X and the Y

chromosomesdupduplicationfrafragile site46, Y

fag(X)(q27.3)Male with fragile X

chromosomeiisochromosome46,X,i(Xq)Female with
isochromosome fro the long arm of the X

chromosome.insinsertioninvinversioninv(3)(p25:q21)Pericentric

inversion of chromosome 3marmarker

chromosome47,XX,+marFemale with an extra unidentified

chromosome.matmaternal origin47,XY,der(1)matmale with

additional der(1) translocation chromosome inherited from his

mother.pshort arm of chromosomepatpaternal originqlong arm

of chromosomerring chromosome46,X,r(X)Female with ring X

chromosomercpreciprocal translocationrobRobertsonian

translocationttranslocation46,XX,t(2;8)(q21;p13)Female with

balanced translocation between chromosome 2 and

chromosome 8, with breaks in 2q21 and 8p13terterminus46,

X,Xq-(pter-->q21:)Female with partial deletion of the long arm

from Xq21 to Xqter (nomenclature shows the portion of the

chromosome that is present)+gain of47,XX,+21Female with

trisomy 21-loss of45,XX,-14,-21,+t(14q21q)Normal female

carrier of a robertsonian translocation between the long arms of

chromosomes 14 and 21; karyotype is missing a normal 14 and a

normal 214p-Chromosome 4 with a on of the short

arm deleted.:break5qter -->5p15:deleted chromosome 5 in a

patient with cri du chat syndrome, with a deletion breakpoint in

band p15::break and

join2pter-->2q21::8p13-->8pterDescription of der(2) portion of

t(2,8)/mosaicism46,XX/47,XX,+8Female with two populations of

cells, a normal karyotype and one with trisomy 8