User:J.abraham.133/sandbox

Topic: Understanding Neurological Diseases (and treatments) by Looking at the Evolution of Humans and the Human Genome.

Works Cited

Azhari, Aziz, Jasmina Ilievska, Paul Fisher, and Naomi Bishop. "An Evolutionary Biology Approach to Understanding Neurological Disorders." Www.intechopen.com. N.p., 20 Apr. 2012. Web. 14 Sept. 2014. This article is full of information relating gene loci and disease phenotypes. Furthermore, evolutionary biology is related to the development of neurological disorders. I would consider this the most fruitful of the articles listed here.

Braak, H., Dr. "Evolution of Neuronal Changes in the Course of Alzheimer's Disease - Springer." SpringerLink. N.p., 1998. Web. 14 Sept. 2014. This article brings molecular genetics into the understanding of Alzheimer’s disease. The progression of the disease and the related gene regulation as a predictor for the onset of the disease. Brown, Betty, M. Oberste, and James Alexander. "Molecular Epidemiology and Evolution of Enterovirus 71 Strains Isolated from 1970 to 1998." American Society for MicrobiologyJournal of Virology. N.p., 2 Sept. 1999. Web. 14 Sept. 2014. This article follows a virus and explains the differences the virus can cause in Humans in relation to its location on the Earth. This article implies genetic drift could be a factor in the virus.

Park, Solip, Jinho Kim, and Juyong Park. "Evolutionary History of Human Disease Genes Reveals Phenotypic Connections and Comorbidity among Genetic Diseases." Nature.com. Nature Publishing Group, 22 Oct. 2012. Web. 14 Sept. 2014. This article claims that there is an evolutionary relationship between diseases phenotypes and the way diseases are classified. The article tries to explain how similar evolutionary constraints in Human genes allow better prediction of the risk of developing a disease.

Perlman, Robert L. Evolution and Medicine. Oxford: Oxford UP, 2013. Print. This book has examples of how natural selection has shaped genetic diseases, and how diseases of the humans in the past have affected the evolution of Humans now. The book presents evolution as a way of understanding current diseases.

https://en.wikipedia.org/wiki/Biochemistry_of_Alzheimer%27s_disease

Although AD shares pathophysiological mechanisms as prion diseases, it should be noted that AD is not transmissible like prion diseases.[15]

Castellni RJ, Perry G, Smith MA (2004). "Prion disease and Alzheimer's disease: pathogenic overlap". PubMed. .

Biochemical Characteristics
The article states, "Levels of the neurotransmitter acetylcholine are reduced. Levels of the neurotransmitters serotonin, norepinephrine, and somatostatin are also often reduced. Glutamate levels are usually elevated." The article does not go into detail about what implications these changes could mean. Are these neurotransmitters, such as serotonin, only reduced in the affected areas of the brain? Are they reduced elsewhere in the body besides the brain? Does the increased Glutamate levels imply that there is too much Glutamate and therefore causes neuro-toxicity?

You need two more suggestions besides going into detail about implications of changed neurtransmitter levels Larson.309 (talk) 17:35, 12 October 2014 (UTC)

Although AD shares pathophysiological mechanisms as prion diseases, it should be noted that AD is not transmissible like prion diseases.

Final Draft
Understanding Neurological Diseases by Examining their Evolutionary Mechanisms JA2189 Tues, 3:00 p.m

Understanding neurological diseases is complex and varied. Between mental illness and physical disabilities, treatments for neurological diseases are found by sequencing the human genome, deep brain stimulation, pharmacology, and can be found on accident as well. Many evolutionary concepts can be applied to uncover the causes and potential treatments for neurological diseases. Most neurological diseases are hereditary, and can be traced in the family, even if no symptoms are present. Alzheimer’s disease, Parkinson’s disease, and schizophrenia have strong heritability and genetics. These diseases, and many other complex diseases, are not controlled by a single gene. Heritability is defined as the ratio of overall phenotypic variation caused by genetic variability. Using a pedigree is a relatively easy way to obtain a statistically unbiased estimate of a disease’s heritability for an individual. If a disease is present that cannot be traced by a pedigree, it is possible it is caused by a de novo mutation. That is, a mutation that the parents do not have. Mutations cause genetic variability, and as a natural force, these mutations can cause neurological disease phenotypes (Azhari 2012). One way to determine genetic variations that cause diseases is using association-based analyses with genetic linkage. Creating databases of genotypic arrays for patients with disease phenotypes can pinpoint the mutations that cause a disease, such as Mendelian diseases (Azhari 2012). Humans have evolved with diseases. Humans have spread from Africa and adapted to new cultures including food and habitat. Positive selection for advantageous alleles in these new environments shows how a difference in ethnicity can make someone more susceptible to disease (Azhari 2012). A good example is sickle cell anemia in African populations. A mutation in the gene responsible for Hemoglobin B provides a resistance to malaria, which is a common killer in Africa. Sickle cell anemia, although less fit in most environments, becomes more fit in Africa and places where malaria rates are high. This example reinforces the theory of positive selection causing different susceptibilities to certain diseases in specific populations that have evolved over time. This is important because studies that use samples must consider the ethnicity of their sample group and relate that to its conclusions. Some neurological diseases are also neurodevelopmental disorders, meaning they are associated with complication during pregnancy or during adolescences of the patient (Azhari 2012). Schizophrenia is thought to be a neurodevelopmental disorder. Evidence that Schizophrenia is a neurodevelopmental disorder includes obstetric complications, diminished social skills, non-drug induced psychosis, protein analysis and gene sequencing (Gupta 2005). Obstetric complications, such as bleeding or hypertension, have an increased association rate with schizophrenia. The molecular genetics behind Schizophrenia includes high-risk genes that are linked to both neurodevelopment and to Schizophrenia. Many proteins responsible for neuronal growth of axons and dendrites are found to have lowered levels in children that develop Schizophrenia. Also, post-mortem studies have shown changes in certain brain regions of patients diagnosed with Schizophrenia. This includes a smaller volume in the overall grey matter volume of the brain. Knowing if a disease is neurodevelopmental can increase diagnosis rates that occur earlier in life, which means treatment or management of the disease can start at the earliest signs of symptoms or even before. Perhaps treatment could even occur during pregnancy (Gupta 2005). Some diseases that have similar phenotypes may have similar evolutionary connections. These diseases have a higher rate of comorbidity. Although not all diseases with similar phenotypes may be related, they can still have very different physiological phenotypes. The rates of these evolutions can actually be split into two groups, slow and rapid. Slowly evolving diseases include the morphological phenotype while rapidly evolving diseases include the physiological phenotypes. Knowing which category a disease is stemmed from could indicate possible treatments that have worked for similar diseases (Park 2012). Neurological diseases are not always caused by genetics. Viruses can even cause neurological diseases. Enterovirus (EV71) can cause disease in the extremities and the mouth, but also could cause encephalitis or poliomyelitis. A study (Brown 1999) that looked at different strains of EV71 across the world shows that even the virus is evolving. EV71 is rapidly evolving, actually at a similar rate to poliovirus. This is important, because by treating the neurological symptoms of EV71 it may be possible to treat or cure EV71 before it ever possibly spreads like the poliovirus once did. Understanding an evolving virus can prevent neurological diseases from occurring (Brown 1999). Other diseases can have evidence of their presence years before symptoms are onset. Alzheimer’s disease is a progressive neurodegenerative disease. Even 25 years before symptoms are onset, observing the cerebrospinal fluid can show an indicator if an individual will develop the disease. Although early treatment may or may not help symptom onset, at least knowing if you will be likely to develop a disease can allow a patient to plan and prepare for the future. However, testing can be painful and is only done if there is a suspicion of Alzheimer’s disease in the family such as a positive pedigree analysis (Braak 1998). Parkinson’s disease, another neurodegenerative disease, involves the depletion of dopamine and dopamine receptors in the brain. Deep brain stimulation (DBS) is a surgical option to help treat Parkinson’s disease. By implanting an electrode into very specific locations in the brain, such as the subthalamic nucleus, and connecting this electrode to a battery located in the chest cavity, the motion control of Parkinson’s disease can be restored in ways that improve the quality of life for the patient. While Parkinson’s disease can have similar phenotypes to other neurodegenerative disease, such as Multiple Sclerosis (MS), its pathophysiology is very different. Surgery for a Parkinson’s patient is less costly than to a patient with MS because MS patients lose significant amount of myelin when under anesthetics (Benabid 2014). This is why understanding and classifying certain diseases can help us treat them without harming patients (Robert 2013). Parkinson’s disease is genetic; however symptoms of Parkinson’s disease and Alzheimer’s disease can also occur from a non-genetic reason. Repeated traumatic head injury can give someone the disease phenotypes of these diseases. Boxer’s and Football players are prone to these. Treatment for this phenomenon can be different than standard treatment for Parkinson’s disease or Alzheimer’s disease, so understanding the reason of symptom onset can help effectively treat a patient. Also, knowing why the symptoms are present can help increase the accuracy of studies that examine neurological diseases (Benabid 2014). Since many Neurological diseases involve genes, sequencing a person’s genome can identify disease-gene correlations. This is not necessarily a feasible method because of the time and cost it takes to do that. New developments in sequencing DNA, such as the 454 Sequencer, helps expedite the process of trying new in vitro treatments for neurological diseases. Because of new, more comprehensive and quicker methods of studying genes, treatments can be deem null and void or plausible much earlier than before. 454 Sequencing has led to a better understanding of the human genome, which means a better understanding of diseases (Rothberg). Overall, we cannot effectively treat the insidious diseases that affect our brains without understanding the molecular genetics and evolution behind these diseases. To know ourselves, we must know our genes. Neurodegenerative diseases, like Parkinson’s or Alzheimer’s, benefit from gene sequencing just as neurodevelopmental diseases like Schizophrenia can. New treatments for these diseases range from new pharmacological methods to deep brain stimulation.

Works Cited Azhari, Aziz, Jasmina Ilievska, Paul Fisher, and Naomi Bishop. "An Evolutionary Biology Approach to Understanding Neurological Disorders." Www.intechopen.com. N.p., 20 Apr. 2012. Web. 14 Sept. 2014. Braak, H., Dr. "Evolution of Neuronal Changes in the Course of Alzheimer's Disease - Springer." SpringerLink. N.p., 1998. Web. 14 Sept. 2014.

Benabid, Alim. "Deep Brain Stimulation." Science Direct. N.p., n.d. Web. 20 Oct. 2014.

Brown, Betty, M. Oberste, and James Alexander. "Molecular Epidemiology and Evolution of Enterovirus 71 Strains Isolated from 1970 to 1998." American Society for MicrobiologyJournal of Virology. N.p., 2 Sept. 1999. Web. 14 Sept. 2014.

Gupta, Swapnil, and Parmanand Kulhara. "What Is Schizophrenia." National Center for Biotechnology Information. U.S. National Library of Medicine, 30 June 0005. Web. 19 Oct. 2014.

Park, Solip, Jinho Kim, and Juyong Park. "Evolutionary History of Human Disease Genes Reveals Phenotypic Connections and Comorbidity among Genetic Diseases." Nature.com. Nature Publishing Group, 22 Oct. 2012. Web. 14 Sept. 2014. Perlman, Robert L. Evolution and Medicine. Oxford: Oxford UP, 2013. Print.

Rothberg, Jonathan, and John Leamon. "Develpment and Impact of 454 Sequencing." Nature.com. Nature Publishing Group, n.d. Web. 20 Oct. 2014.

Sickle-cell anemia and human evolution
A mutation in the gene responsible for HBB protein provides a resistance to malaria, which is a common killer in Africa. Sickle cell anemia, although less fit in most environments, becomes more fit in Africa and places where malaria rates are high. This example reinforces the theory of positive selection causing different susceptibilities to certain diseases in specific populations that have evolved over time. This means that Humans of different ethnicity have evolved seperately. People of African descent have evolved to have higher rates of the gene HBB because the heterozygous individuals have a misshaped red blood cell that is not as severe as homozygous people, disallowing malaria to attach to the blood cell. Studying point mutations that cause diseases, such as Sickle-cell anemia, can help trace human evolution.