How to Conquer a Abnormality— What is the relative size of a chromosome to a to a to a of DNA?

University of Texas Health Science Center at San Antonio, School of Medicine The Clinical Research Center

What is the relative size of a chromosome to a gene to a base pair of DNA? Special points of interest:

 DNA base pair numbers Here is the same clinical karyotype that we have seen before. As you know by now,  Over 300 on chro- these short little actually mosome 18 pack a very long molecule of DNA. But just how long is it?  76,117,153 base pairs on chromosome 18

 Football field analogy As we previously saw, this diagram would be like assigning every word in the depicts the structured packaging of cookbook with consecutive numbers. Karyotype using light mi-  DNA into a chromosome. In this Then if you were told that word 10,452 croscope technology vs. depiction, the pairs of blue chemical should be teaspoon instead of tablespoon, new molecular-based subunits are the base pairs. The you would know exactly which word they techniques chromosome has a long string of meant. In this same way, assigning con- base pairs. secutive numbers to each base pair allows discussion about very specific Inside this issue: You can define a position along this locations along the DNA molecule. DNA molecule by a base pair number. Chromosome 18 contin- 2 As with our cookbook analogy, this ued

Football Field Analogy 2 Chromosome 18 genes 3 Summary Looking at the chromosome in base pair scale demarked in terms of genes, there are over million base pair units— 300 genes on chromosome 18. beginning with 1 at the top and And one gene may be thousands or showing 10 million base pairs, tens of thousands of base pairs 20 million etc. all the way to long. base pair 76,117,153.

In the diagram to the right of the To the right of that, the green karyotype is the official banding and white lines depict the loca- pattern of chromosome 18, shown tions of the genes. Now let’s in shades of gray. The centro- zoom in on one section so you mere is dark orange. can see it more clearly.

To the right of that in black is the

How to Conquer a Chromosome Abnormality— Page 2 What is the relative size of a chromosome to a to a gene to a base pair of DNA?

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 . 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 Football Field Analogy small but clinically significant changes, You should be able to appreciate by relative size of genes to base pairs to the now that the identification of a very various detection methods. new molecular- small deletion or duplication in a In order to appreciate the scale, let’s use karyotype actually represents a based techniques something we are all familiar with— change in a large number of genes. especially when talking about distance—a have been Something has to be massively football field. If we line up chromosome wrong in order to be seen under a developed.” 18 along a football field, we have a visual microscope. In order to detect small aid that is useful and easy. but clinically significant changes,

new molecular-based techniques One yard of this football field-sized chro- such as FISH and microarrays have mosome would be within the gold box been developed. shown near the top of the chromosome. Let’s zoom in on that location. Here we want to demonstrate the

0 USP1 One yard would be the length of the The large blue box indicates the 18p11.21 TYMS chromosome within the gold box. On size of the smallest deletion or 18p11.21 METTL4 average this one yard length would duplication that could be found 2 include 3 to 4 genes, but could be as using the conventional cytogenet- many as 8 to 10 or as few as none. One ics that produces the karyotype MYOM1 18p11.31 yard also equals 760,000 base pairs. that you have seen many times. TGIF This box includes five million base One inch in the red box would be 21,222 4 pairs and would cover 6.5 yards base pairs of DNA. So even if you on the football field. This means stretch chromosome 18 out to be the that a deletion or duplication that length of a football field, you would still would be undetectable in a karyo- 6 LAMA1 need a microscope to distinguish single type could include as much as 20 base pairs. genes and 5 million base pairs. UTHSCSA—Department of Pediatrics For more information, you may contact the authors and principal investigators of the Chromosome 18 Clinical The Chromosome 18 Clinical Research Center Research Center at the phone numbers or email shown to the left. MSC 7820 7703 Floyd Curl Drive San Antonio, TX 78229-3900 Authors & Principal Investigators: Phone: 210-567-5321 Jannine D. Cody, PhD and Daniel E. Hale, MD Fax: 210-567-0919 E-mail: [email protected]

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. Information provided by The Chromosome 18 Clinical  Very useful for the detection of whole chromo- Research Center to: some changes and large rearrangements be-

tween chromosomes.

 Commercially available in all cytogenetic labor- atories.

http://www.chromosome18.org/ 210-657-4968