You Are Studying a Human Cell and Examining the Chromosomes. You Know That They Are in the

Abstract

Have you lot always looked at a calico cat and wondered how it got its multicolored coat? Or have you wondered why more boys than girls are colorblind? The combination of colors in the cat, and the reason some people are more than likely to have traits like colorblindness or to get certain diseases, all comes dorsum to one little part of the body, the X chromosome! Learning more about how our genes make united states unique helps scientists understand how we avoid certain diseases. Nosotros wanted to know how the X chromosome affects disease in cells. We used mice to study how one of the X chromosomes turns itself off in females and how this procedure shapes the design of the body, in health and disease.

Why Are Chromosomes Important?

Your trunk is fabricated up of trillions of cells, each containing deoxyribonucleic acid (Deoxyribonucleic acid). DNA is made up of thousands of genes , which are the "instructions" for things like eye color or whether you are more probable to get certain diseases. In your cells, DNA is wrapped tightly into structures called chromosomes. Each human being jail cell has 46 chromosomes, or 23 pairs (since chromosomes come in pairs, with one from your mom and the other from your dad). The 23rd pair of chromosomes are called the sexual practice chromosomes , and those chromosomes are called either Ten or Y. Males have one X sex chromosome and i Y sex chromosome, while females have two X sex activity chromosomes. The genes on the X chromosomes are important for how the body grows and functions.

What is X Chromosome Inactivation?

Females accept two X chromosomes in each cell! Scientists discovered that, when female babies are developing, they take a special mechanism that randomly turns off one of their two X chromosomes [1]. When 1 X turns off, the other is yet working and its genes tin can be expressed, which ways those traits tin show up in the female's body. This process of turning 1 10 chromosome off is called 10-chromosome inactivation (XCI). Since non every cell turns off the same 10 chromosome, the cells can express X-chromosome genes differently from each other. This is called cellular mosaicism . Cellular mosaicism gives females more diversity than males, pregnant that they have more options during development and more means to preclude disease [2]. We will describe this more, practice not worry!

Imagine a calico cat—they are almost always female. Female calico cats have ii versions of a gene for their coat colour. Both versions are located on their X chromosomes. Patches of fur are either orange or blackness, depending on which X chromosome is turned off in that patch of hair cells. Imagine that the Ten from the mom carries the orange fur gene, and the X from the dad carries the black fur cistron. If 1 patch on a kitten'due south dorsum has the mom's X chromosome inactivated, so that patch of fur will be black! But what if some peel cells on a spot on the kitten'south tail have the dad'southward X chromosome inactivated? Those cells will express the orange gene and the fur will be orangish (Figure 1). XCI just happens in female person mammals, including humans, and affects almost all genes on the X chromosome.

• Figure 1 - On the left is a motion picture of a typical calico cat.
• The diagram shows how orangish and blackness fur color genes on either of the X chromosomes result in different fur colors. Male person cats only have i X chromosome, then they are either black or orange. Female cats carrying 2 orange 10 chromosomes will exist orange and females with two blackness 10 chromosomes volition be blackness. All the same, due to XCI, females carrying one orangish and one black Ten chromosome will take orange and black patches (adjusted from Slutz [3]).

Why is Studying X Chromosome Inactivation Of import?

Many genes can undergo changes, called mutations, which, in some cases, tin can make a person more probable to go sure diseases. Diseases caused by mutations in genes on the X chromosome are chosen Ten-linked diseases . Call back, males practise not feel XCI considering they only take one X chromosome. And then, if males have a disease-causing gene on their X chromosome, it will exist agile and more likely to cause illness. However, XCI helps protect females from Ten-linked diseases. Imagine a girl has a salubrious copy of a factor on ane Ten chromosome and a mutant copy of the same gene on her other 10 chromosome. If the X chromosome with the mutant copy is turned off due to XCI, then the 10 chromosome with the healthy copy will stay active and limited the cistron properly. This does not mean she would non get sick, but information technology will increment her chances of not getting the diseases related to the mutant gene. This is why studying XCI is important! The patterns of disease gene expression that event from XCI might determine how severely someone is afflicted by an X-linked disease.

Ane example of an Ten-linked disease is crimson-green colorblindness. Scarlet-greenish colorblindness is a illness in which the affected person cannot tell red from dark-green. Another example of an X-linked affliction is called Norrie illness, and that is what nosotros studied. Norrie affliction affects the eyes and can cause incomprehension in boys. Interestingly, Norrie illness also affects girls, but more mildly. Norrie disease is caused past a mutation on the X-linked factor called norrin. We wanted to empathize how XCI affects girls who comport a bad re-create of the Norrie disease cistron. Knowing these patterns for different diseases can assist scientists learn more almost why people go sick or stay healthy.

How Did we Study X Chromosome Inactivation and Norrie Disease in our Experiment?

The pattern generated by XCI happens to cells everywhere in the female'south body very early in evolution. That means the trillions of cells making up the body all limited genes from only one X chromosome or the other. A whole organ, part of a muscle, or a whole side of the brain could have any pattern of expressed "mom Ten-linked genes" and "dad 10-linked genes." That is pretty absurd! We wanted to meet if patches of cells in a female'due south body are more "mother expressing" or more "father expressing." Hither is how we did it:

We used mice in our experiment, considering they are very easy to work with in the laboratory. We used colored dyes to stain the X chromosomes from the mom and the dad in female mice. The "mom Ten chromosome" was stained light-green and the "dad Ten chromosome" was stained scarlet. The red or green dye but stained the X chromosome that was working to express genes—the X chromosome that had not been turned off by XCI. We studied healthy female mice and female mice with Norrie affliction [4]. Nosotros could run into the ruby and green colors in the cells using a special microscope. This told us which cells in the mouse had an active "dad X chromosome" or an agile "mom Ten chromosome." Nosotros stained cells all over the mouse, like the heart, the tongue, the skin, and the eyeballs! Looking at cells in the eyeball was especially interesting to us, since Norrie disease affects the eye and causes blindness. After taking pictures of the unlike body parts, we examined the photos and discussed why these different patterns of XCI were important to our experiment. The red and green cells in Figure 2 are examples of the cool patterns XCI can create!

• Figure 2 - These images were taken using a microscope that tin observe the red and green dyes the mouse chromosomes were stained with (adapted from Wu et al. [iv]).
• XCI creates dissimilar patterns all over the body. (A) Female person mice siblings bear witness dissimilar X chromosome inactivation patterns beyond their entire bodies. (B) XCI creates "patchy" patterns in female skin cells. (C) XCI creates an uneven pattern in the middle cells (retinas) of a mouse with Norrie disease. The XCI blueprint of left vs. the right retina shows how the severity of the disease can be different between the 2 eyes.

Figure 2 shows some of the results from our experiment. The red and green cells in this effigy show how XCI can be unlike within one female animal, or between siblings. In Figure 2A, fifty-fifty though these two sisters share the exact same DNA from their parents, one is almost all dark-green and one is almost all ruddy. This means that the green mouse is expressing more often than not "mom X chromosome" genes and the "dad X chromosome" genes are near all inactivated. The carmine mouse has almost all its "dad X chromosome" genes activated, and the "mom X chromosome" genes inactivated. This is how XCI tin cause diversity between organisms.

Figure 2C shows the retina of the eyeballs from a female mouse with Norrie disease. You can encounter that the left retina has a lot of scarlet, significant that the "dad X chromosome" is very agile in that eye. The right retina has a lot of green, so the "mom X chromosome" is active in the greenish areas, but inactive in places where y'all see carmine cells! And then, what does this tell us about how XCI affects Norrie disease? Let u.s. say that the red-stained "dad X chromosome" carries the diseased copy of the Norrie affliction gene. This means that, in the cells that are reddish, the diseased X chromosome is active and expressing the disease gene. The more cells that limited the disease-causing gene, the worse the disease will exist! And then, from this image, we can see that the left heart is more diseased than the right middle in this mouse. This explains why the affliction might only bear upon one eye in a female patient or might impact both eyes differently. XCI also explains why two female person patients might both have Norrie illness, merely one has astringent symptoms and incomprehension, while the other has only mild symptoms. This was a very exciting discovery from our experiment.

What Else Did We Larn About XCI?

We also studied how XCI shapes the female person body during evolution. In our experiment with the mice, we found that sometimes the cells expressing light-green or cherry-red would be evenly scattered (nigh like red and green sprinkles on a cupcake). In other areas, the red and green cells formed patches or were symmetrical, as in Figure 2B. Nosotros wondered why sometimes the colors were scattered and other times they were in bunches. From our research, we realized that the pattern of XCI depends on the style each tissue in the body develops. When an animal is growing, some cells, like blood, move all over the body. Others, like peel cells, usually exercise not motility as well much during evolution. This means that blood cells have a chance to mix with each other and have a higher take a chance of looking like red and green sprinkles. For cells that stay in a certain surface area, like skin cells, they may share the same inactive X chromosome because they came from the same dividing jail cell. This leads to the patches of red and green, just like the patchy fur pattern on the calico cat or in the eyes in Norrie illness! Amazingly, the pattern varies even among siblings, which means that even identical twin females will have very different gene expression patterns on the X chromosomes.

How Tin Our Study Aid Science and Medicine?

What does this all mean? How can our discovery of the pattern of XCI in cells help people? Well, we studied a fascinating biological activity that occurs in all female mammals. The technique nosotros used, colour-coding the X chromosomes, could exist very helpful for scientists researching X-linked diseases. We hope that this study inspires others (maybe future scientists, like you!) to look at how XCI affects brain development. Information technology would be interesting to understand how XCI influences differences in the left and correct sides of the encephalon or whether XCI causes differences in brain structure between males and females. Nosotros believe that learning more than near the part XCI plays in affliction will improve our understanding of many diseases. Futurity enquiry may fifty-fifty inspire a therapy to turn on the inactivated X chromosome, to assist females with X-linked diseases.

Glossary

Gene: ↑ A slice of Deoxyribonucleic acid that guides development of the body and produces traits. Genes are passed down from parents to their children.

Sex Chromosome: ↑ A deoxyribonucleic acrid (Dna) molecule that codes for a set of genes that decide the sexual activity of an individual (10 and Y Chromosomes).

XCI: ↑ X chromosome inactivation is a biological process where one of the two copies of the X chromosome becomes inactivated in female person mammals.

Cellular Mosaicism: ↑ The presence of cells, in one individual, with different genes or features. Cellular mosaicism is acquired by XCI.

X-linked Affliction: ↑ Genetic diseases in which the illness-causing cistron exists on the X chromosome.

Cistron Expression: ↑ The procedure by which information from a cistron is used to create the physical characteristics of an animate being.

Retina: ↑ The inner layer of the heart that is normally sensitive to in most vertebrates. The office of the retina is similar to the flick of a camera!

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or fiscal relationships that could be construed as a potential conflict of interest.

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Original Source Article

↑Wu, H., Luo, J., Yu, H., Rattner, A., Mo, A., Wang, Y., et al. 2014. Cellular resolution maps of Ten chromosome inactivation: implications for neural development, role, and disease. Neuron 81:103–19. doi: 10.1016/j.neuron.2013.x.051

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References

[1] ↑ Lyon, M. F. 1962. Sex chromatin and gene activity in the mammalian X-chromosome. Am. J. Hum. Genet. 14:135–48.

[2] ↑ Migeon, B. 2006. Females Are Mosaics: X Inactivation and Sex Differences in Affliction. Oxford, United kingdom: Oxford Academy Press.

[iii] ↑ Slutz, S. 2019. Ten-inactivation Marks the Spot for Cat Coat Colour. Scientific discipline Buddies. Bachelor online at: https://www.sciencebuddies.org/science-fair-projects/projection-ideas/MamBio_p022/mammalian-biology/10-inactivation-cat-coat-color (accessed April 19, 2019).

[4] ↑ Wu, H., Luo, J., Yu, H., Rattner, A., Mo, A., Wang, Y., et al. 2014. Cellular resolution maps of 10 chromosome inactivation: implications for neural evolution, part, and illness. Neuron 81:103–nineteen. doi: x.1016/j.neuron.2013.10.051

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Source: https://www.frontiersin.org/articles/468286