Download Podcast 4 Handout - Chromosome 18 Registry and Research Society

How to Conquer a Chromosome Abnormality—
What is the relative size of a chromosome to a to a gene to a base pair of DNA?
University of Texas Health Science Center at San Antonio, School of Medicine
The Chromosome 18 Clinical Research Center
Special points of interest:
 DNA base pair numbers
 Over 300 genes on chromosome 18
 76,117,153 base pairs on
What is the relative size of a chromosome to a gene to a base pair of DNA?
Here is the same clinical karyotype that
we have seen before. As you know by now,
these short little chromosomes actually
pack a very long molecule of DNA. But just
how long is it?
chromosome 18
 Football field analogy
 Karyotype using light microscope technology vs.
new molecular-based
techniques
Inside this issue:
Chromosome 18 continued
2
Football Field Analogy
2
Summary
3
As we previously saw, this diagram
depicts the structured packaging of
DNA into a chromosome. In this
depiction, the pairs of blue chemical
subunits are the base pairs. The
chromosome has a long string of
base pairs.
You can define a position along this
DNA molecule by a base pair number.
As with our cookbook analogy, this
would be like assigning every word in the
cookbook with consecutive numbers.
Then if you were told that word 10,452
should be teaspoon instead of tablespoon,
you would know exactly which word they
meant. In this same way, assigning consecutive numbers to each base pair
allows discussion about very specific
locations along the DNA molecule.
Chromosome 18 genes
Looking at the chromosome in
terms of genes, there are over
300 genes on chromosome 18.
And one gene may be thousands or
tens of thousands of base pairs
long.
base pair scale demarked in
million base pair units—
beginning with 1 at the top and
showing 10 million base pairs,
20 million etc. all the way to
base pair 76,117,153.
In the diagram to the right of the
karyotype is the official banding
pattern of chromosome 18, shown
in shades of gray. The centromere is dark orange.
To the right of that, the green
and white lines depict the locations of the genes. Now let’s
zoom in on one section so you
can see it more clearly.
To the right of that in black is the
How to Conquer a Chromosome Abnormality—
What is the relative size of a chromosome to a to a gene to a base pair of DNA?
Page 2
Chromosome 18 continued
Here are the chromosome bands on the left
and the base pair scale on the right. The
green and white lines indicate the positions
of the genes. The abbreviations for the gene
names are shown for some of the genes to
the right of the black line. What is not shown
here is that genes have length. The DCC gene
is actually very long, one of the longest in the
entire human genome. It takes up most of
the space between the genes above and
below. What you can appreciate here is that
genes are not evenly distributed. This means
that you cannot make a correlation about a
certain number of base pairs representing a
certain number of genes.
“In order to detect
small but clinically
significant changes,
new molecularbased techniques
have been
developed.”
Football Field Analogy
You should be able to appreciate by
now that the identification of a very
small deletion or duplication in a
karyotype actually represents a
change in a large number of genes.
Something has to be massively
wrong in order to be seen under a
microscope. In order to detect small
but clinically significant changes,
new molecular-based techniques
such as FISH and microarrays have
been developed.
Here we want to demonstrate the
relative size of genes to base pairs to the
various detection methods.
In order to appreciate the scale, let’s use
something we are all familiar with—
especially when talking about distance—a
football field. If we line up chromosome
18 along a football field, we have a visual
aid that is useful and easy.
One yard of this football field-sized chromosome would be within the gold box
shown near the top of the chromosome.
Let’s zoom in on that location.
One yard would be the length of the
chromosome within the gold box. On
average this one yard length would
include 3 to 4 genes, but could be as
many as 8 to 10 or as few as none. One
yard also equals 760,000 base pairs.
One inch in the red box would be 21,222
base pairs of DNA. So even if you
stretch chromosome 18 out to be the
length of a football field, you would still
need a microscope to distinguish single
base pairs.
The large blue box indicates the
size of the smallest deletion or
duplication that could be found
using the conventional cytogenetics that produces the karyotype
that you have seen many times.
This box includes five million base
pairs and would cover 6.5 yards
on the football field. This means
that a deletion or duplication that
would be undetectable in a karyotype could include as much as 20
genes and 5 million base pairs.
0
USP1
TYMS
18p11.21
18p11.21
METTL4
2
MYOM1
18p11.31
TGIF
4
6
LAMA1
UTHSCSA—Department of Pediatrics
The Chromosome 18 Clinical Research Center
MSC 7820
7703 Floyd Curl Drive
San Antonio, TX 78229-3900
Phone: 210-567-5321
Fax: 210-567-0919
E-mail: [email protected]
For more information, you may contact the authors and principal investigators of the Chromosome 18 Clinical
Research Center at the phone numbers or email shown to the left.
Authors & Principal Investigators:
Jannine D. Cody, PhD and Daniel E. Hale, MD
Our Motto
To provide individuals and families affected by
chromosome 18 abnormalities with comprehensive
medical and educational information with a focus
on treatment options.
We are on the web!
http://pediatrics.uthscsa.edu/centers/chromosome 18/
Summary
In summary, the cytogenetic analysis that generates
a karyotype using the light microscope technology is:

A useful tool because all the chromosomes can
be visualized at once.

However, not very specific because of its low
resolution.

Very useful for the detection of whole chromosome changes and large rearrangements between chromosomes.

Commercially available in all cytogenetic laboratories.
Information provided by The Chromosome 18 Clinical
Research Center to:
http://www.chromosome18.org/
210-657-4968