Tag Archives: down syndrome

Reading Your Blueprint: Karyotyping

DNA is  what makes us who we are. It identifies us. The government uses it to control us. Well, that last one isn’t quite true…yet. Still most of us, even those of us who should know better, treat DNA as if it were magical fairy dust that wizards in lab coats use to answer questions. But the only difference between the wizards and you is some knowledge and equipment. This blog will help with the knowledge part.

There are three main ways to use DNA to tell something about an individual: Karyotyping, DNA fingerprinting, and Genome sequencing. I’ll go over Karyotyping in this post and tackle the other methods later.  Karyotyping is basically looking at the chromosomes of a cell as it’s dividing. Cells divide to make new cells, but in order to make sure each new cell has everything it needs, everything has to be copied, including the genetic information. Unless the cell is a bacterium (or an archeum), it will keep its genetic information in a sort of ball of denser material called a nucleus. Most of the time this ball is all we see of the cell’s DNA, but if we add a dye and watch the cell divide, we can see several strange, threadlike structures, or bodies, that are colored by the dye. These “colored bodies” are the chromosomes, named after the Greek “chromo” for colored and “soma” for body. A chromosome is actually DNA wound up around proteins and then wound up again and again until it becomes a tight tangled mess, similar to what happens if you twist a coiled telephone cord.

As you look at  chromosomes under a microscope, in other words, you are actually looking almost directly at DNA.  Normally the chromosomes are haphazardly arranged around the nucleus of the cell, but after taking a picture of them, you can rearrange them so that they’re aligned the same way and in order from largest to smallest. This is a Karyotype.

Usually a lab worker who wants to karyotype a person’s blood, will look at some white blood cells, which are easier to work with for a variety of reasons, and wait for themto start dividing. Then, he or she will use a drug such as colchicine or vinblastin to stop the cell from dividing completely. This allows the technician to look at all the chromosomes under the microscope and analyze them using dyes that bind to different genes. The lab worker or another scientist or technician can then compare the karyotype of one individual to another to see what differences they are in where the dye shows up.

The drugs used to stop the cells from dividing have interesting histories. Colchicine started out as the active ingredient in an herbal remedy extracted from autumn crocuses to treat gout and inflammatory arthritis. Crocus extract was used as such as far back as 1500 BCE though it was only isolated from crocus extract in the late 1800’s. Colchicine is still used to treat severe cases of gout today, however, the difference between an effective dose and a toxic one is rather small, so takers of the drug have to be careful.

Chromosomes of a cell. Vinblastin or colchicine used to keep them from separating.

Vinblastin also comes from a plant extract, this time from the madagascar periwinkle plant. The plant was originally crushed into a tea, and researchers noted that people who drank the tea had a lower white blood cell count, leading researchers to look into the active ingredient as a possible treatment for diseases that affect white blood cells.

White blood cells are primarily responsible for the body’s immune response, which causes inflammation, the primary complaint of gout and arthritis sufferers. These cells also  affect a number of diseases, including cancer. White blood cells use microtubules to initiate movement, and all cells use microtubules to separate chromosomes as they divide. Cochicine and vinblastin both inhibit the production of microtubules, which is why the drugs are useful in karyotyping as well as a number of other diseases.

The easiest thing you can do with karyotyping, after determining species, is determining sex. A normal human being has 23 pairs of chromosomes and sex is determined from the 23rd pair. Genetic females have two longer chromosomes, called “X” chromosomes here, while for genetic males one of the chromosomes is shorter and called a “Y” chromosome. Sometimes a person might have two or more X chromosomes along with a Y chromosome in a condition called Klinefelter’s syndrome. There are also a number of other possibilities, such as XXX or even XXXY. All these scenarios usually result in learning disabilities, and regardless of how many X chromosomes there are, if there is a Y chromosome the person will be physically male. These situations where there are more than two sex chromosomes are examples of aneuploidy.

Karyotype of a normal male. From biology.iupui.edu

The word “aneuploid” comes from four Greek words mashed together: “an-” for not, “eu” for good,”ploos” for fold, and “oidis,” which means form or type. So all together you have “not good fold type,” a set of chromosomes that is not correctly paired. This sort of situation can occur in other chromosomes as well, such as in the case of Down syndrome, the second most common inherited  form of mental retardation, where there is an extra copy of chromosome 21.

In biological terms, “-ploid” refers to how many complete sets of chromosomes there are. The normal number of copies for a set of chromosomes is two, so most cells are called diploid. Sperm and eggs only have half the normal amount of chromosomes, so they are haploid. Plants and some other organisms can have more than two sets of chromosomes, making them polyploid. While polyploidy can occur in human fetuses, it never results in birth. In fact no vertebrate animal can be polyploid.

A normal x chromosome on left, fragile x on right.

Fragile X is the most common inherited form of mental retardation, and while it is not a aneuploidy disorder, diagnosticians can also identify it using a karyotype. In fragile X one of the x chromosomes looks thinner in an area that has a long string of the same DNA sequence. Because of this repeated sequence, a protein required for normal development can’t be produced properly and the neurons of the brain cannot form the proper connections as a result.

Diagnosticians can tell that someone has Fragile X from the way a certain area of a chromosome is affected naturally, however they can also tell other genetic attributes by how the chromosome is affected by the dye they use. Giemsa, the most common dye used for karyotyping, will concentrate in different bands on the chromosome, which you can see in the picture of the normal male karyotype above. By comparing where these bands show up between different karyotypes, researchers can begin to find abnormalities and differences that may have something to do with how a person looks, acts, or feels.

Other labeling techniques have also been used to get more information from chromosomes. Especially exciting is the work done on telomeres, which can be labeled using a protein attached to a fluorescent marker. These are the ends of the chromosomes, which are made up of repeating patterns of DNA that act like the aglets of shoelaces, keeping the chromosome from shortening prematurely. Telomeres have been found to be  linked with the aging process. Although the telomeres will shorten and lengthen throughout life, various stresses can cause them to shorten more than usual. It seems the older we are, the shorter our telomeres get. If we can figure out how to lessen the shortening process, we may find a cure for aging itself.

TELOMERES cap the ends of chromosomes. Image: WIKIMEDIA COMMONS/NATIONAL HUMAN GENOME RESEARCH (user GIAC38)

Suggestions? Corrections? Questions? Observations? I’m trying to cover a lot of ground here without letting things get too complicated, so I’m bound to make some mistakes. Please feel free to comment on this post or email me at zorknot (at) gmail.com about what I’ve written.