X Chromosomes & Genetic Mosaicism
X-Chromosomes. Everybody’s got one! Or two. The X chromosome is so fascinating to study because in most cases, multiplicity of chromosomes is a huge problem. Case and Point: Down Syndrome, sometimes called trisomy 21, because of the multiplicity of chromosome 21. This chromosome is actually extremely small, and just one extra causes a cascade of problems in the body. So how does the female body deal with the extra X? After all, it’s an extremely large chromosome, full of important information. The solution: Barr bodies! In every cell of the female mammal, one X-chromosome randomly “shuts down.“ The DNA becomes methylated, basically wound down into a squished up package of genes. This occurs sometime during embryo formation. When it occurs is actually somewhat random as well. More on that later. So, one chromosome gets shut down. How do the cells then replicate? Well, before mitosis starts to begin, the Barr body becomes acetylated, and voila! The chromosome is ready for replication.
The interesting thing is, mom and dad’s contributing X-chromosomes are shut down with equal probably. EXCEPT, in the case of the placenta. The cells of a female fetus closest to the placenta will shut down their X-chromosome received from dad. The common thought of why this happens has to do with protecting the fetus from mom’s immune cells. Perhaps if the cells more closely resemble mom’s, the fetus is more protected.
Another consequence of Barr body shut down is in the case of heterozygosity for X-linked traits. Assuming that Barr body shut down is random, all heterozygotes for a particular X-linked trait will exhibit a sort of mosaicism. The most common example of this is the tortoiseshell cat. The allele for cat color is located on the X-chromosome, and cats can be either orange or black. (Of course, other colors and patterns exist, and multiple genes contribute to cat color; however, for the sake of this simplicity, we will just stick to the main ones.) Since male cats have only one X-chromosome, they can only be orange or black. For a heterozygous (with respect to color: an orange X and a black X) female cat, Barr body inactivation leads to a spotted appearance of both black and orange fur. Calico patterns form when Barr body inactivation occurs earlier in gestation. (The white color is derived from a genetic phenomenon called epistasis, which will be discussed in a later article). The embryo is smaller, and therefore, the patches of color are larger. Once a Barr body is formed, that same X-chromosome will be inactivated during the remainder of the cells life, even after replication. Additionally, the replicated cells will also exhibit the same Barr body. A male tortoiseshell is extremely rare; in fact, the only way a male cat can be tortoiseshell is if it is Klinefelter: XXY.
For the human case, mosaicism exists in a condition of the sweat glands, hypohidrotic ectodermal dysplasia. And here’s the shocker: IT’S X-LINKED!!! Persons with this disorder fail to produce functioning sweat glands. Females heterozygous for this disorder will form patches of functioning and non-functioning sweat glands. A living mosaic.
Barr bodies are one of the hottest lines of research right now, and though they are extremely interesting, there is still much to be discovered about them.
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