User:Taylor V. Anderson/sandbox

Imani Carter, Ceon Brown, Taylor Anderson, Stephen Borders

17 November 2018

Salem

Wiki Article

ALX3

ALX3 was first discovered by a group of scientists, led by Hopi Hoekstra, a biologist from Harvard University, that investigated how stripe patterns form in animals. They investigated the Rhabdomys pumiliom, commonly known as the African striped mouse because of the alternating colored stripes observed on its back. One of the members of the team, Ricardo Mallarino, discovered that the stripes were formed during embryogenesis in the mice. Melanocytes, the specialized cells that produce the pigments in the skin, were not active in areas where the lighter stripes were observed. They then researched the genes active in those areas using RNA sequencing. They discovered that ALX3 was expressed in the light hair areas but not in the dark hair areas. They found that all mice expressed the gene on their abdomen but only the African striped mouse expressed it on its back, hence why the strips appear. Protein-DNA binding was then performed to determine where the ALX3 protein binds on the DNA. ALX3 binds to the promoter and represses MITF, which allows transcription to take place when making melanocytes. More tests were performed to confirm the function of ALX3 within the African striped mice. The gene was observed in other rodents such as the North American chipmunks and deemed responsible for the similar outcomes. The differences in evolution amongst the species did not hinder the similarities in the expression of the gene. This lead the team to believe that ALX3 may have the same effect in mammals. However, further studies must be completed to confirm that ALX3 is responsible for the same in other mammals.

ALX3 has an important role when it comes to the development of a fetus. Without this gene or protein we as humans would miss an key factor in the human body, our nose. The function of the ALX3 gene is to make instructions for the ALX3 protein. This proteins molecular function has specific sequence DNA binding, which means it selectively and non-covalently interacts with DNA of a specific nucleotide composition (“Gene Ontology and GO”). This protein is part of the homeobox protein family. A homeobox is a sequence in our DNA that includes so many bases pairs found in a gene. This gene codes for a protein that finds to the DNA and controls its gene expression (“Homeobox”). Homeobox is responsible for making sure the process of formation during fetus development has the correct body structures. The ALX3 protein is what forms the head and the face but paying special attention to the nose which develops around the 4th week. This gene s a transcription factor that attaches to DNA and controls the actions of certain genes. During the developmental stage of life, this gene regulates growth and division and movement, making sure the cells grows and stops at it specific times (“ALX3 gene”). Aside from being the protein that creates the face, when coded wrong it can cause multiple mishaps and disease to occur, including cancer.

ALX3 a gene found on chromosome one is responsible for constructing facial features near the mouth and nose region and a wide area of other “smaller” disorders that are quite common. This particular gene has a couple disorders that can affect normal human life negatively and some are linked to mild mental retardation, however some of these issues can be fixed and an individual suffering from some of these issues at the earliest stage in life can be fixed with facial construction surgery or plastic surgery. For example cleft nose or frontonasal malformation, which is recessively inherited. Cleft nose is a disorder in which the skin, cartilage or bone does not form correctly between four and eight weeks when a child is in the womb. This disorder is very obvious from birth and is easily diagnosable however surgical reconstruction can help fix this problematic phenotype by using skin from other places of the body and cartilage or something to mimic cartilage. A disorder of ALX3 can also cause skull malformation, which can cause a lot of complications in facial features and possibly inhibit areas for the brain to develop and grow. These skull malformations can cause a couple of different looking formations, for example the bone between the two front teeth, a shelf in the base of the back of the skull, and even small dents in the forehead. These disorders have been found in many ethnic families and they do not seem to trend with just one family. Some of these disorders rather unfortunate however an individual can still get along in life most of the time and have a pretty normal life despite looking different. Not all who have disorders in the ALX3 gene will have a mild mental retardation, many have been found to have a disorder but have a very normal mental capacity.

As explained, ALX3 codes for making a protein that is a member of the homeobox family that helps with development but with mutations of the gene it can cause frontonasal dysplasia. This effect the development of the facial structure causing deformities mostly in the nose and moth area. On a genetic level, this is caused by the ALX3 protein not functioning properly or to not do so in entirety. Since the ALX3 protein is a transcription factor which implies that it binds to the DNA in order to control genes that preform cellular division and growth without this regulator it is bound to have negative effects in the development stages with serious consequences. This causes “clefts” which is openings in the nose and can also cause improper formation of the skull going as far as malformations of the tissue that joins the halves of the brain which can cause mental disabilities instead of just physical. Another serious possibility is the possibility of incomplete formation of the skull to a degree where there is only skin covering the head where bone should be. Whereas many of these may seems to more of a cosmetic issue along with intellectual disabilities the misfunction of the ALX3 gene can cause death. Depending on the issue, this autosomal recessive inheritance condition can be fatal especially without immediate medical attention for serious cases. This abnormality has three different types which all carry their own consequences but most commonly is type one which is the condition described above but the other two could include hair loss, genital abnormalities in males, eyes that are missing, and wide-set ears. Frontonasal dysplasia is a very rare autosomal condition, but this is the serious result of misfunction of the ALX3 gene and protein.

References

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