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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