Chromosome 5

December 6, 2017

Chromosome 5 is the fifth largest autosomal chromosome and typically, humans have two; one from their mother and one from their father. There are close to 1700 genes and 180 million base pairs on Chromosome 5. Scientists have identified 97% of the genes on Chromosome 5 so biologists do know a lot about it. There are quite a few diseases, sixty six to be exact, associated with the genes on this Chromosome, and fourteen more which have been identified but have yet to be mapped. The diseases located on Chromosome 5 include; attention-deficit hyperactivity disorder (ADHD), Cri du Chat syndrome, Diastrophic dysplasia, Dilated Cardiomyopathy, Inflammatory bowel disease, Parkinson’s disease, Perrault syndrome, and Sotos syndrome, just to name a few. Three other diseases associated with genes on Chromosome 5, which will all be explained in this article are Asthma, Spinal Muscular Atrophy, and Cockayne Syndrome (Mandal, 2014).

Asthma is a disease that many people have heard of, but that still remains a bit of a mystery to biologists. The phenotype of this disease is characterized by significant trouble breathing and inflammation of the airways. While it is thought that the “Asthma genes” are fairly common, it is impossible to know the exact prevalence of these genes. The three genes associated with Asthma are 5q31-q33, but this disease is not necessarily caused by the certain genes associated with it; rather, the people that carry these genes are simply more susceptible to developing Asthma. Another factor that makes pinpointing the genetic cause for Asthma difficult is the ability for some people to carry these genes and never develop Asthma during their entire lifetime. The development of Asthma is caused by a number of environmental factors including smoking and air pollution. It can also be developed at any point in a person’s life, and there is no way at any given time for doctors to predict if a person will or won’t develop asthma later on in their life. (Levitt, 1995).

While the exact prevalence of the 5q31-33 genes that cause susceptibility to Asthma is not fully known, there are several effective methods of treatment and prevention that have been developed for people who have this disease. Asthma is an allergic reaction that occurs in the bronchial tubes which causes inflammation, making it hard for a person to breathe. There are antibodies called IgE antibodies, which bind to the IgE Fc receptor and cause the allergic reaction. This inflammation can be prevented with a drug called DARPin E2_79, which is a protein inhibitor. By binding and blocking the IgE Fc Receptor, this drug stops the antibodies from binding and causing the allergic reaction and inflammation in the bronchial tubes (Kim, 2012). More drugs and treatment methods for Asthma are continually developed and marketed as our knowledge of this disease evolves.

Spinal Muscular Atrophy is a degenerative disease which is autosomal recessive, and therefore this condition is fairly uncommon. It is estimated that about one in forty people are heterozygous for the SMA gene, so it is lucky that this gene is recessive. The gene that causes this disorder is located on 5q13.2. Because Spinal Muscular Atrophy is recessive, a person would have to be homozygous for this gene. That means that a person would have to receive a gene for Spinal Muscular Atrophy from each of their parents in order to be affected by the gene. Two carrier parents who are heterozygous for the SMA gene would have a 25% chance of this gene affecting one of their children. While the vast majority of cases of this disease are the result of a homozygous offspring from two carrier parents, there is a rare mutation in which the recessive gene for Spinal Muscular Atrophy will be manifested and affect a person who is heterozygous for the gene.

There are three phenotypes of Spinal Muscular Atrophy; Type I, Type II, and Type III, which are ranked, beginning with Type I by earliness of onset. There also exist two subtypes of Spinal Muscular Atrophy; Type 0, which causes death before 6 months of age and Type IV, which is onset during late adulthood. Spinal Muscular Atrophy is characterized by progressive degeneration of muscles and the spinal cord, and has a shortened life expectancy for Types 0-III. The true amount of expressions of the SMA gene in humans is unknown because in some cases death is caused in utero, and those do not always get recorded (Verhaart, 2017).

The cause of Spinal Muscular Atrophy is a mutation that affects the SMN1 neuron. In some cases the neuron is completely missing, in other cases it is just defective and does not code proteins correctly. The SMN1 codes the SMN (Survival Motor Neuron) proteins and there is another neuron called the SMN2 which also codes the same proteins. There is a therapy currently in trial for Spinal Muscular Atrophy which stimulates the SMN2 neuron code more of the SMN proteins. It is believed that this increase in production by SMN2 can help make up for the deficit caused by the defect of SMN1. This therapy does not completely stop or reverse Spinal Muscular Atrophy, but it has been shown to dramatically slow the progression of the disease (Wertz, 2016).

Finally, Cockayne Syndrome is named as such because the last name of the man who first recorded this disease in 1936 was Cockayne. Because this disease is autosomal recessive, it is rare and there are currently only 180 reported cases worldwide. Little is known about the biology of Cockayne Syndrome and for unknown reasons, this disease progresses much slower with some people and much quicker with others. There are multiple phenotypes of Cockayne Syndrome and most of them affect each person at a different rate. Cockayne Syndrome can usually be detected immediately after birth. The characteristics of Cockayne Syndrome are brain calcification beginning post natal, mental retardation, persistent scaly, itchy rashes, skin discoloration, photosensitivity (extreme sensitivity to sunlight), premature aging, dwarfism (growth retardation), symptoms similar to those of dementia (forgetfulness, moodiness, difficulties learning), and premature death. Some people with Cockayne Syndrome can live into adulthood, but unfortunately many people die before adulthood (Rapin, 2006).

There are currently no cures for people who have Cockayne Syndrome but there are potential therapies which are currently being studied or under trial. One cause of Cockayne Syndrome is believed to have to do with the efficacy of the mitochondria in individuals with Cockayne Syndrome. Patients who have Cockayne syndrome have showed more “mitochondrial DNA oxidative damage” than those who do not have Cockayne Syndrome. This is caused by a defect in the proteins of the mitochondrial membrane, affecting its ability to perform redox reactions and leaving the cells more vulnerable to oxidative damage. There is a potential therapy drug that is not fully developed yet, which is designed to increase the effectiveness of the proteins in the mitochondrial membrane, which will in turn create more stability of the mitochondrial membrane. This stability helps to increase “ROS (reactive oxygen species) levels” (Pascucci, 2012). This therapy does not cure or reverse the effects of Cockayne Syndrome but it is believed to slow the progression on the disease.

In conclusion, medicine and technology are advancing at an increasingly high rate. Luckily, there are ways to treat Asthma and prevent Asthma attacks, even though the exact genetic effects of the 5q31-q33 genes are not fully understood and the prevalence is difficult to study. Spinal Muscular Atrophy is a hard disease to research, and imaginably a much harder disease to suffer with. While there is no known cure, there is a plethora of technology that has been developed to help people with Spinal Muscular Atrophy get around and also great technology to help those who care for people that are affected by the SMN1 mutation. There is also hope with medicines that are in trial for slowing the progression of Spinal Muscular Atrophy and maybe more potential treatment in the future as our society’s knowledge of medicine increases. Cockayne Syndrome is also a hard disease to research as the effects are painful and generally unpleasant. The positive note is the amount of research that is currently underway about Cockayne Syndrome and the potential drug therapy that is currently being tested by biologists. The existence of genetic diseases such as these, reinforces the need for genetic testing and it is not hard to see why genetic testing is becoming increasingly common.

RESOURCES

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Mandal, A (February 6, 2014). What is Chromosome 5? and Chromosome Related Diseases. News-Medical.Net. Retrieved from: https://www.news-medical.net/health/What-is-Chromosome-5.aspx and https://www.news- medical.net/health/Chromosome-5-Related-Diseases.aspx

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Pascucci, B., Lemma, T., Iorio, E., Giovannini, S., Vaz, B., Iavarone, I., Calcagnile, A., Narciso, L., Degan, P., Podo, F., Roginskya, V., Janjic, B., Van, B., Houten, Stefanini, M., Dogliotti2, E., and D’Errico, M. (2012). An altered redox balance mediates the hypersensitivity of Cockayne syndrome primary fibroblasts to oxidative stress. Aging Cell 11, pp520–529. retrieved from: http://web.a.ebscohost.com.ccco.idm.oclc.org/ehost/pdfviewer/pdfviewer?vid=6&sid=59d06a55-0ad1-4a65-8619-ee7d6aa436b2%40sessionmgr4009

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Verhaart, I.E.C., Robertson, A., Wilson, I.J., Aartsma-Rus, A., Cameron, S. Jones, C.C., Cook, S.F., Lochmüller, H. (2017) Prevalence, incidence and carrier frequency of 5q–linked spinal muscular atrophy –a literature review. Orphanet Journal of Rare Diseases 12;124.