Tag: gene expression

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Molecular markers identified for autism, schizophrenia, and depression

Some psychological disorders, such as schizophrenia, tend to be highly heritable, meaning that the disorder is often passed down generationally within a family. Schizophrenia, for instance, is 60-87% heritable; if you were to have schizophrenia, there’s a 60-87% chance that one of your immediate relatives will develop symptoms, too. Similarly, major depressive disorder is 30-40% heritable. Therefore, in order to treat these disorders, its necessary to look at the genes involved. A February 2018 study published in Science found that there is significant overlap in gene expression between autism spectrum disorder, schizophrenia, and bipolar disorder, as well as an overlap between schizophrenia, bipolar disorder, and major depression. The strongest relationship was between schizophrenia and autism spectrum disorder.

Consider gene expression as a construction company. A construction company has a stockpile of materials: concrete, glass, cement, wood, nails, etc. The company has a crew of workers, and the crew is capable of building a variety of houses and apartment buildings. The construction company is analogous to the use of DNA by cells in the brain. The DNA is like the stockpile of materials. The materials are required to build anything, but the possible combinations of materials are endless. The RNA transcription mechanism in the cells is like the crew. The crew chooses which materials to use, and determines how much of each item is necessary for the project. In cells, this system is called “gene expression.” Every cell in the brain has the same DNA, or the same starting materials, but each cell has a different construction crew that decides to use the materials slightly differently; some build houses, some build apartment buildings, some build garages.

Instead of examining the DNA, or the building materials in over 700 cadaver brain samples used in the study, the researchers looked at the gene products, or what the construction crews built. It is unknown whether the gene products found in the brains caused the disorder symptoms, or gradually developed throughout life as the consequence of the disorders. But the study provides useful information regarding what proteins and structural factors manifest in disordered brains, and this information can be used to trace back to an origin point. Director of the UCLA Center for Autism Research and Treatment, and author of the study Daniel Geschwind said, “These findings provide a molecular, pathological signature of these disorders, which is a large step forward.”

The scientists found biological markers that tend to distinguish a brain with autism, for example, from the average brain. In the case of autism spectrum disorder, the study reported an increased activation of the CD11 gene, while another gene called CD2 was especially active in the brains suffering from depression. Additionally, the study mapped gene expression commonalities between brains with the same disorder, essentially establishing a molecular blueprint that can be recognized for diagnosis, and treated more effectively at the molecular level.

Sources:

Gandal, M.J., Haney, J.R., Neelroop, N.P., Leppa, V., Ramaswami, G., Hartl, C., Schork, A.J., Appadurai, V., Buil, A., Werge, T.M., Liu, C., White, K.P., CommonMind Consortium, PsychENCODE Consortium, iPSYCH-BOARD Working Group, Horvath, S., & Gerchwind, D.H. 2018. Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 359: 693–697.

Hopper, Leigh. 2018. Autism, schizophrenia, bipolar disorder share molecular traits, study finds. UCLA Newsroom. Retrieved Feb. 26 from http://newsroom.ucla.edu/releases/autism-schizophrenia-bipolar-disorder-share-molecular-traits-study-finds.

Seidel, D.C., Bulk, C., Stanley, M.A. 2017. Abnormal Psychology: A Scientist-Practitioner Approach (4th Edition). Pearson Education [print].

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Staying Balanced: Sour Taste Buds Linked with the Ventricular System

In January 2018, a study published by the American Association for the Advancement of Science presented a surprising link between the sense of taste and the sense of balance. While trying to determine which genes are responsible for certain taste buds to ascertain sourness, scientists found the same gene at work in the inner ear.

Lemon slices
Lemon slice. Credit: GDJ; Creative Commons Clipart.

When you think “sour,” you might think about puckering at the juice of a slice of lemon, but scientists think about pH levels. Sourness is actually a measure of acidity, due to the fact that a substance is acidic if it contains lots of H+ ions (hydrogen atoms with a positive electrical charge), which is also a mark of low pH. There are different kinds of taste buds: some recognize sweetness, some recognize saltiness, etc. The taste buds that recognize the sour *tang* of Sour Patch Kids contain ion channels that allow H+ ions to flow into the taste bud cell and send a signal to the brain that says, “Wow! This is sour!”

To ascertain which gene or genes are responsible for expressing the proteins necessary for building the H+ ion channels in sour taste bud cells, researchers at the University of Southern California used a mouse model. They compared the transcriptome of mice with sour taste buds with the transcriptome of mice without them. The transcriptome is a collection of all the RNA in a particular cell, and is an indicator of proteins that are being generated and built by a cell. When 41 potential proteins were identified in the sour taste bud cells, but not found in the other taste bud cells, the scientists knew one of them must play a role in the mechanism for detecting sour tastes.

The researchers implanted the potential genes into human embryonic kidney cells (HEK-293) or the female egg cells of a frog model (Xenopus oocytes). Then, the kidney cells and egg cells were flooded with an acidic solution and observed for H+ ion currents. The researchers noticed that the gene Otopetrin1, abbreviated as Otop1, was the only gene to produce an ion channel that permitted H+ ions to pass through.

The gene Otop1 is part of the otopetrin gene family, which happens to be known for the development and function of the vestibular system. The connection is clear when mice with Otop1 mutations exhibited issues with spatial orientation and balance. They could not properly right themselves or swim. Furthermore, the mice with Otop1 mutations had weaker currents of H+ ions in the taste bud cells, which suggests that the mice were not able to fully taste sourness. The scientists at USC hypothesize that Otop1 regulates an optimal pH level in the inner ear during development.

“We never in a million years expected that the molecule that we were looking for in taste cells would also be found in the vestibular system,” senior researcher Emily Liman said. “This highlights the power of basic or fundamental research.”

The Otop1 gene also produces H+ ion channels in the heart, uterus, adrenal gland, mammary gland, and in fat tissue, although the role of H+ ion channels in these regions is not understood. Further research may uncover more intriguing and unanticipated connections within our genetic makeup.

Taste bud cells
Taste bud cells, magnified and artificially colored. The red portions denote cells that detect sour tastes, while the green portions mark cells that detect umami, sweet, or bitter tastes. Credit: Yu-Hsiang Tu and Emily Liman.

Sources:

Tu, Y.H., Cooper, A.J.,Teng, B., Chang, B.R., Artiga, D.J., Turner, H.N., Mulhall, E.M., Ye, W., Smith, A.D., & Liman, E.R. 2018. An evolutionarily conserved gene family encodes proton-selective ion channels. Science [published online] DOI: 10.1126/science.aao3264.

Gersema, E. 2018. Surprising discovery links sour taste to the inner ear’s ability to sense balance. USC Press Room. Retrieved Feb. 18 from http://pressroom.usc.edu/surprising-discovery-links-sour-taste-to-the-inner-ears-ability-to-sense-balance/.