N Engl J Med. 2010 Mar 10.
Whole-Genome Sequencing in a Patient with Charcot-Marie-Tooth Neuropathy.
Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA.
In this paper researches address a new question that is the hope for pharmacogenomics based therapy. The identification of individual genes that alter alter the course of a patients care is constantly growing. What these studies add to our arsenal of knowledge is often a probabilty that an individual has for a certain outcome.
The study above is a different beast, here reseachers address what specific alleles (sequence) a patient has and draws conclusions as to what the appropiate treatment course might be. This approach is only possible as population genetics and sequencing technology have matured.
If you are a Tox. student I would like to know what you think about the following.
What different forms can this disease take?
What form is identified in this study, and what allele is used to determine this?
What do you think about using genomic sequencing like this?
Would you want your genome sequenced? Why or why not?
Gillespie Lab 
In order to demonstrate the effectiveness of whole genome sequencing, scientists were able to use Charcot- Marie-Tooth neuropathy, a hereditary motor and sensory neuropathic disorder. This disease can take either a demyelinating form (type 1) which affects the myelin sheath, or an axonal form (type 2) which affects the nerve axons. In this examination, the specified form is type 1, demyelization and the alleles used to determine whether a person had CMT were PMP22, 11 MPZ, PRX, GDAP1, and EGR2, common genes found in CMT patients. In order to properly sequence the genes of the participants in this examination, scientists used a “sequencing by oligonucleotide ligation and detection” system (SOLiD). This system involves ligation-based sequencing and a two base encoding procedure where four fluorescent dyes were used to tag various combos of di-nucleotides. I believe that this is yet another tremendous breakthrough in medical technoology because instead of basing diagnosis on inference, past cases, and inaccurate tests, researchers can now pinpoint the sequence that is the cause of the patient, that is IF he or she actually has the disorder. We can now compare not only phenotypes, but genotypes as well. I would like to have my own genome sequenced for my reference. I can be sure of any health complications I have and I can modify my lifestyle to be careful not to turn on certain genes and turn off other ones. Although all the sequences of the human body have not been found/ distinguished enough, I’m looking forward to its completion.
Charcot Marie Tooth disease is acquired in two forms, primary myelinopathy (CMT type 1) which destroys axons and primary axonopathy (CMT type 2) which kills nerves. CMT type 1 is inherited in a dominant, recessive and x-linked manner, while CMT type 2 is inherited in a dominant and recessive manner. However, there also exist autosomal dominant intermediate forms of CMT that have axonal neuropathy and demyelinating properties.
To my understanding, mutations in SH3TC2, PMP22 and other genes related to CMT disease cause susceptibility to the carpal tunnel syndrome. Thus, a possible way to uncover the mystery is through sequencing the genome which will ultimately lead to sequencing individual genomes and keeping them on record. Sequencing the entire genome is a rather tedious process, however, with newer technology on the rise and newer knowledge about the human genome, the process should not take very long to complete. Whole genome sequencing can help establish whether the additional 69 SNPs at the SH3TC2 locus and 3146 SNPs at the other 39 neuropathy associated gene loci attribute to neuropathy phenotype.
Personally, if whole genome sequencing can help us establish more links among allele mutations and the type of diseases they cause, then it should definitely get done. It is a great gateway to the future and can be extremely useful in terms of even predetermining phenotypic conditions at the genetic level as well as creating new ways to treat these genetic disorders. But there are complications, after all we are dealing with genomes of individuals of different regions and ethnic backgrounds. How then is it possible to sequence a standard human genome model? With insufficient knowledge in the field of genome sequencing and perhaps a hint of ignorance, I can only suspect the process of whole genome sequencing to be a very complex process, where lots of crucial decisions must be made. Wisely.
My decision on whether if I want my genome to be sequence or not is still pending. I feel that having my genome sequenced would definitely lead to an invasion of my privacy. On top of that, where will my information be stored? How will that information be made available to my doctors? And are there more complications? I feel that although sequencing the genome is a useful method to correlate allele mutations to diseases, it is the blueprint of our identity. So for that reason I don’t think I would like my genome to be sequenced.
The Charcot Marie Tooth Disease is an inherited peripheral neuropathy with two forms: a demyelinating form affecting glia-derived myelin and an axonal form affecting the nerve axon. CMT disease has been used as a model disease to describe genetic heterogeneity, and determine the human diseases while scrutinizing the gene mutations.
The whole-genome sequencing approach used in this proband helped us identify the cause of the disease as compound heterozygous mutations in the SH3TC2 gene and thus to delineate the specific biologic basis of disease in the family. Genes involved in CMT disease consist of PMP22, SH3TC2 and many more. Both of the SH3TC2 mutations, when heterozygous, have phenotypic consequences that can be detected by electrophysiological means. The Y169H missense variant segregates with an axonal neuropathy, whereas the nonsense R954X mutation is associated with sub clinical evidence of the carpal tunnel syndrome, therefore, haploinsufficiency of SH3TC2 may cause susceptibility to the carpal tunnel syndrome. And the whole-genome sequencing of other members of the proband’s family might help clarify whether the additional 69 SNPs at the SH3TC2 locus and 3146 SNPs at the other 39 neuropathy –associated gene loci examined can modify the highly pnetrant Y169H and R954X mutations and thereby influence the neuropathy phenotype.
Genome sequencing like this is a great technological advance that lays out the significant points about the individual’s genome on genetic level and makes one aware about the possible outcomes. But this approach involves an irksome task, which might hinder the possibility of getting any individual’s genome sequenced. Personally, I feel that a little modification is required to improve the sequencing technique for it to be available to every person on this planet so that the technology might be applied efficiently and easily.
I would definitely want my genome to be sequenced and know about the phenotype but only when the technology has further revolutionized in terms of genome sequencing to avoid confronting the tedious process of the method applied currently.
Charcot–Marie–Tooth disease is one of the most common inherited nerve disorders. CMT is caused by mutations in proteins that are needed for nerve cells to function. Since nerve signals are conducted by an axon with a myelin sheath wrapped around it, CMT mutates these axons and myelin sheath. Thus there are two forms of this disease- Demyelinating form or type 1 (mutates glia-derived myelin) and the Axonal form or type 2 (affecting the nerve axon). Charcot–Marie–Tooth type 1 is identified in this study by using compound heterozygous mutations in the SH3TC2 gene. DNA sequencing was performed with the use of the SOLiD (Sequencing by Oligonucleotide Ligation and Detection) system. PCR (polymerase-chain-reaction) was also used to amplify Exons 5 and 11 of the SH3TC2 gene.
Using whole genome sequence is a breakthrough for medical diagnosis. Although very complicated, it seems to be very efficient and accurate in finding alleles that causes the disease. Technological improvements have enabled the process to be very cost-efficient and as stated in the article, the entire effort would currently cost less than $50,000. Considering these factors along with other diagnostic approaches, such as a clinical-testing panel that screens for a copy-number variant that commonly causes Charcot–Marie–Tooth disease (which appears to cost more and yet less efficient) it’s safe to say that whole genome sequence is the better way to approach disease diagnosis. I would definitely like to have my genome sequenced since knowing my sequence; my physicians would be better able to treat me. It will lead to identifying disease causing alleles quickly and thus altering the consequences of me getting infected with that disease.
Charcot-Marie-Tooth Neuropathy is an inherited peripheral neuropathy. It comes in 2 forms. Type 1 is a demyelinaitng form that affects the glia-derived myelin and Type 2 is an axonal form that affects the nerve axon. This disease has been used to describe genetic heterogeneity. Mutant alleles of this disease can segregate in a dominant or recessive manner in autosomal chromosomes or can be X-linked. In this study Type 1 which is the demyelinaiting form is identified. This is done by using compound heterozygous mutations in the SH3TC2 gene, then using SOLID to sequence the DNA and then PCR to amplify the exons of the gene.
I think using genomic sequencing like this is a great advancement in technology and very beneficial. We are able to compare phenotypes to their genotypes. Sequencing the genome helps us identify the different forms and mutations of genes and can help us see what diseases they cause. This could be useful in preventing or help curing certain diseases. Personally I would want to have my genome sequenced. I feel it is beneficial so I can be informed of a disease I may have or will have and if possible help treat it or alter my life to adjust to it.
This week’s paper takes a look at whether or not whole genome sequencing can help medical professionals predict/detect genetic disorders in patients. Up until now, this process has proved to be difficult because of the many types of mutations, variants, and expression levels that can occur in DNA. The authors of this paper focus on a family with a recessive form of Charcot-Marie-Tooth disease, a disorder often used as an example of “genetic heterogeneity.”
CMT disease can take on two different forms. Type 1 destroys the myelin sheath of nerve cells while type 2 affects nerve axons. This paper focused on CMT Type 1 and the researchers take a closer look at genes PMP22, MPZ, PRX, GDAP1, EGR2, and SH3TC2. The genomes of the test subjects were sequenced using the SOLiD (Sequecing by Oligonucleotide Ligation and Detection) system. The accuracy of this system for every 50-base read is 99.94%. It utilizes ligation-based sequencing, and a two-base encoding method where four fluorescent dyes tag certain combinations of dinucleotides.
The researchers found that the SH3TC2 gene was more significant than others in detecting susceptibility to CMT disease. The authors found that mutations in the SH3TC2 gene when heterozygous has phenotypic consequences which can promote CMT disease and carpal tunnel syndrome. The researchers found that haploinsufficiency of SH3TC2 (having only one functioning copy of a gene as opposed to two) increases susceptibility to carpal tunnel. This insufficiency may also result in mutations of other genes related to CMT such as PMP22. The researchers also determined that whole genome sequencing of more family members would clarify whether SNPs on SH3TC2 and other genes associated to neuropathy modify certain mutations that influence neuropathy phenotype.
I think that genomic sequencing shows a lot of promise for the future of medical technology. Genomic sequencing will probably help doctors and scientists diagnose patients, as well as predict diseases and determine better methods of treatment. As genomic sequencing of patients becomes more widespread, the idea of personalized medicine which we discussed earlier in the semester will become more of a reality. As scary or weird as it may seem, our genome contains an insurmountable amount of information which would be helpful to doctors. Nowadays, doctors and insurance companies constantly talk about “preventative care.” What could be more preventative than sequencing your genome and knowing exactly which diseases you’re susceptible to and how you can avoid their development?
I’m not so sure if I am for or against my genome being sequenced. It would be scary to hear if I am susceptible to developing cancer or any other fatal disease, but then at the time same time it would motivate me to live a healthier lifestyle. I would also want to make sure that my genome would remain in the right hands, before you know it, someone may try to clone you! If genome sequencing becomes more widespread and its benefits more well known, I would be open to doing it.
The general idea of this weeks paper is the exploring of genomic sequencing, with new technological advances and information scientists are able to discover a lot more of the human body and the way it works. A team of scientists interested in the potential of whole genomic sequencing used a family who contained the recessive form of Charcot-Marie-Tooth disease and sequenced the whole genome of the proband to conduct their experiment.
Charcot-Marie-Tooth disease has dual forms, Type 1 and Type 2, Type 1 a demyelinating form which effects myelin and Type 2 the axonal form which affects the nerve axons. The scientists in this paper focused on the most common form of the disease which is Type 1 and the gene of focus were PMP22, SH3TC2 , 11 MPZ, PRX, GDAP1, and EGR2. Scientists were able to pinpoint the heterozygous causative allele’s in the SH3TC2 gene and with this experiment they were also able to discover that this family was susceptible to neuropathy and carpal tunnel syndrome.
I believe using genomic sequencing for such a purpose and in such a manner is a wonderful idea and is a step in the right direction for science. Having the ability to pre determine and anticipate complications in individuals could save enormous money on healthcare expenditures and do very well for the economy and on a more health concerning note, individuals would not have to even go as far as to suffer the symptoms of certain diseases or take drugs unnecessary to their treatment. Whole genome sequencing could very will give power to the long awaited personalized medicine.
I would be more than happy to get my genome sequenced it would potentially save me a lot of money, suspense and time. I believe it would be beneficial because if I know that I am prone to suffering from a certain disease I can gear my lifestyle against the development of that disease and try to reduce the chances of me developing it. I do not believe ignorance is bliss in such a case although I do understand there is a safety and privacy concern.
In this paper, the concept of whole gene sequencing was studied through sequencing a family who possessed the sequencing that cause Charcot –Marie- Tooth Neuropathy. Charcot Marie Tooth neuropathy is a neuronal disease in which the nerves are being damaged in one of two different forms. This first form is called myelinopathy. In this form, the Schwann cells around the nerve cells are degrading, causing the axons of nerve cells to have no protective covering. The second form is called axonopathy. In this type the protective covering isn’t the problem; instead the nerve itself is dying, causing neuronal problems. By having the protective covering on the axons and the nerves degrading, the axons begin to lose their function. By losing their functions, nerve impulses are unable to travel their full distances; from the central nerve to the feet.
In this study, the form that was studied in the family was the recessive form of the Charcot Marie Tooth disease. The allele that was used was the SH3TC2 allele because it was found that there were two mutations in the proband in this heterozygous allele. These alleles were sequenced using a method of fluorescent tagging to two nucleotides at a time to try and identify the mutations. It was found when sequencing of the heterozygous alleles that the mutations are the cause of the neuropathy conditions, including the condition of carpal tunnel syndrome.
I think that this type of genomic sequencing is beneficial for all people because it would create a field of more personalized medication and would also help to identify diseases by the specific mutations. Right now, treatments for certain health problems can only be 40% effective for those receiving the treatment. This occurs because some of the mutations of one disease can overlap with one of another. By having this specific sequencing, treatment would be able to be more specific and give a more positive and effective outcome in helping the patient when fighting a specific health problem.
Although I believe that whole genome sequencing would be beneficial, I do think that it shouldn’t be public knowledge. If whole genome sequencing was done for everyone, I believe that each person should have access to their sequence and would be able to provide it to doctors when necessary. I think that one’s own DNA and the mutations that could exist is someone’s own personal business and shouldn’t be exposed to everyone. There is no reason for people to be able to access other people’s genome sequence and in my opinion could only cause problems for people.
Overall, I really enjoyed reading this paper. I felt the abstract was very helpful in providing insight and a clear overview of what was going to be discussed in laymen’s terms. I think the concept of whole genome sequencing is very interesting and is definitely something that I’m sure we will be seeing in the future whether it be more technology towards it or sequencing everyone’s whole genome.
This study is based on the disease called Charcot–Marie–Tooth also known as CMT. It’s an inherited
peripheral neuropathy which has two forms. Type 1 CMT is a demyelinating form, which means to destroy or get rid of the myelin sheath; and affects the glia-derived myelin and an axonal form. Then type 2 of CMT is the affect towards the nerve axon.
The method describes that the study was based on Type 1 of CMT and three effected siblings. The results turned out to be that exons 5 and 11 of the SH3TC2 gene nucleotide mutation results in
elimination of the restriction site for TaqI. It was found that at the SH3TC2 gene, there were two mutations. One was a missense mutation and the other a nonsense mutation which were to be found in the CMT disease. In my eyes, this genome sequencing is a good idea. Like what we spoke about in class, many diseases do not have a tipping point to what causes the diseases. I think everyday on the news I’ve heard something like drinking 2% milk causes breast cancer or eating asparagus can lead to melanoma; and I thought scientists were crazy. But now I understand why they do so many tests and come up with such bizarre results, its because they don’t know where to begin. Genome sequencing is a start. I believe it to be the beginning of many cures and answers to unsolved diseases. What’s best for the future and figuring out these diseases. It’s our job to improve people’s health, prevent disease from spreading, and do whatever it takes to cure those from being sick. I wouldn’t mind getting my genome sequenced. It’d be helpful for me in the future and to know what diseases could be genetically passed down to me. It’s like taking precautions. Besides with the world constantly advancing in technology and such, I wouldn’t be surprised if in a few years everyone’s genome would be sequenced.
Charcot-Marie-Tooth Neuropathy can either be in the form of demylination and an axonal form. This study identified the demylination form in the SH3TC2 gene. Being able to use genomic sequencing to identify genetic disease is very useful in my opinion and I definately think we should be able to use it on a large scale. If it were possible, I would get my genome sequenced because I’d like to know if I have a genetic disorder, especially if I don’t have any phenotypic indications. I believe it’ll be really worthwhile in the long run, especially when planning for a family.
The Charcot-Marie-Tooth an inherited peripheral neuropathy disease has been identified to occur in two different forms: a demyelinating form which affects the glia derived myelin, and type 2 which affects the nerve axon. In this paper scientist focused more on the first type of the disease, since it is the most common form. The most common alleles related to this form of the disease are PMP22, SH3TC2, 11 MPZ, PRX, GDAP1, and EGR2. This study proved that when the SH3C2 has a heterozygous mutation, the disease has a phenotypic consequence such as carpal tunnel syndrome.
From the paper I got a first hand look at what whole gene sequencing may bring about when it relates to diagnosing illnesses. The accurate results this paper gave made me feel confident that if this technique is mastered, one would not have to be afraid to go through therapies. Doctors would be able to cure illnesses more readily and patients would not suffer from painful tests and secondary effects of drug treatments. Therefore my belief is that whole gene sequencing is the next great approach when trying to identify diseases.
In my family I have had many relatives die of many serious illnesses such as: cancer, diabetes, and heart conditions. These deaths made think if I would be susceptible one day to such illnesses. So I would be happy to have my genome sequence and be ready for any illness that could affect me.
Inherited peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease takes two different forms. Type 1 is demyelinating form from gene deficiency of producing myelin and the type 2 is axonopathy, damaging function of exons.
This paper focuses more about the CMT type 1 with using SOLiD system. SOLiD (Sequencing by Oligonucleotide Ligation and Detection) uses ligation-based sequencing and a two-base encoding method.
SH3TG2 protein has responsibility for myelination or axon-glia interactions and the researchers especially studied the SH3TG2 mutations. In SH3TG2, they found the missense mutation Y169H and the nonsense R954X which affect CMT. According to their result based on genomic sequencing of a family who has CMT disease, the children (who have both Y169H and R954X) have CMT type 1 diagnosis. The children, who have only the R954X, have no CMT disease. However, a family member, who has Y169H, has Axonal neuropathy.
Genomic sequencing is epochal method to approach genetic inheritance disease, for insistence CMT disease. It will help to diagnose the disease more accurate in the future. Like CMT, it has different causative forms, but has same phenotype (weakness of muscle, wasting, and loss of sensation).
Genomic sequencing will contribute to effective treatment throughout the diseases that we are having question about the cure. It will help prescribing right doses of drug or diagnosing treatment adequate for the disease, so the medicines reduces the adverse effects and the waste of time for finding right treatment. However, I believe that genomic sequencing will give bad influence at the same time too. We know that a specific gene sequence is related to a certain disease. However, we cannot say the person who has gene sequence can get sick 100% because we always consider the mutation of genes and environmental facts. In the other words, the doctors would make wrong diagnosis and it will bring bad result consequently. Also, I believe that genomic sequence will affect the marriage because nobody wants to marry a person who has disease. If genomic sequencing will be generalized in the future, people will ask the genomic sequence of their future spouses for preventing service for ill family member. Therefore, I do not want my genome sequenced.
Researchers had decided to examine the whole-genome sequencing for the diagnosis in a patient with Charot-Marie-Tooth (CMT) disease to get a closer look at single ‘disease genes’. This concept and the concept of a genetic heterogeneity is foggy to me but what I understand from it is that there has to be a mutation in at different loci on the same gene. CMT is an inherited peripheral neuropathy with two forms known as demyelinating form and axonopathy or axonal neuropathy. Demyelination is the degeneration of the myelin sheath which is the fatty substance that protects nerves which has long fibers called axons that makes sure that the messages being communicated among these axons is not lost in its pathway. This defect causes problems in nerve impulse conduction. Axonopathy is the disorder that disrupts the normal function of the axons which can lead to weaknesses muscle functions or death depending which type is present. The mutant alleles of this disease “can segregate in an autosomal dominant, recessive, or X-linked manner. The single base variants (SNPs) and copy-number variants at a certain loci make the human susceptible to CMT and mutations in another loci cause recessive disease.” The CMT has different symptoms but it has certain characteristics like distal symmetric polyneuropathy (disruption of normal functioning of axons) and distal muscle weakness and atrophy resulting in foot problems. They also applied next-generation sequencing to develop the probability that an individual will have an outcome by observing the inherited neuropathy.
So through whole genome sequencing of the proband helped us identify the cause of the disease from the compound heterozygous mutations in the SH3TG2 gene which helps assemble the protein complexes and the involvement of protein-protein interaction. In mice, they found that this gene was expressed in the Schwann cells which is similar to the glail cells (provide support, nutrition, participate in signal transmission, and maintain homeostasis). When mice lack this gene, there are gaps in the myelin sheath (demyelination). The mutations of these genes, when heterozygous, cause variable phenotypes because the Y169H missense variant segregates with an axonal neuropathy and the R954X mutation causes carpal tunnel syndrome due to haploinsufficiency. CMT disease may have a similar concept with the SH3TG2 and the PMP22 alleles. Studies in whole genome sequencing should continue to advance if they want to clarify how the additional 69 SNPs influence the SH3TG2 locus and 3146 in the other 39 loci related to neuropathy affect the phenotype.
These researchers believe that using “whole-genome sequencing over targeted, exon-captured approaches” would lead to more accurate diagnosis information and “rapid identification of the alleles that cause disease.”They are correct because in using this method, they could find the ‘causative’ mutations that may not be in the coding regions only and in capturing copy number variants which are also factors of entities, like alleles, that can cause disease. Whole genome sequencing was made possible through gene array analysis which gave researchers the opportunity to analyze the different expression of mRNA sequences (even in different species). This also led them to analyzing of copy-number variants in the proband as well as the identification of DNA substitutions, small insertions, and deletions in every type of genetic region.
I do think that getting my genome sequence would be very beneficial because by analyzing my genome sequence, a scientist in pharmacogenomics would have the ability to make the personalized medicine I need for any situation or circumstance in my life. Knowing, literally, everything about a person due to their genomic sequence is an efficacy, which is the goal of the field of pharmacogenetics, can be beneficial to finding a cure for just about anything and even improving “worn-out” cells that humans generate as they get old. However, after watching futuristic movies that may have corrupted my head, I believe that we may use genome sequencing to our advantage, or in the wrong way, in order to stay alive longer. Of course, it is normal to be afraid of death but there are too many humans on earth and this may sound horrible, but we have to die some day to make room for the humans born now, today, and tomorrow. It’s fine if we use these methods at a young age but seventy and eighty year olds… other than that, whole- genome sequencing from the use of gene array analysis will definitely improve and continue to improve gradually as we continue to discover the way our body functions.
Charcot- Marie- Tooth Disease is hereditary disease of the nervous system. It is caused by mutations in motor and sensory proteins and mostly destructs the myelin sheath, which is responsible for proper axonal transport. CMT can be categorized as either being type I (genetically dominant, X-lined or recessive and affects the myelin sheath); or type II is either genetically dominant or recessive and affects the nerve axon.) There are also mixed categories and genetic subtypes of CMT. The study was conducted in a family that contained a recessive form of the CMT genes by examining four affected siblings and four non-affected siblings. A physical examination of muscle weakness, wasting and deep tendon reflexes were examined. They found localized mutations in the SH3TC2, PMP22, MPZ and several other genes are related to CMT disease that also cause an increased risk to the development of carpal tunnel syndrome. These genes can be mapped as a neuropathy phenotype and used to study genetic sequencing. Charcot Marie Tooth disease has been studied as a model to genetic sequencing. It is used to describe genetic heterogeneity, as a way to investigate the importance of modifying genes when determining different disease.
Genomic sequencing in my opinion, sounds like a tedious project, that can and will be time consuming and very expensive. I however do feel that despite the negatives, this form of research and genetics can open up an entire new understanding of human biological disease and ailments. In the case of CMT by mapping out the genome, one can determine all the ins and outs to the disease, while figuring out a way to prevent of treat illnesses at the gene level and create personalized medicine. I would not contest to having my genome sequenced because I think it will be beneficial to know what genetic mutations I contain in my genes and I can better understand my personal susceptibility to certain diseases. I do believe by doing this we can better unlock the secrets to diseases of the CNS, cardiovascular system, diabetes, heart disease, high blood pressure and cancers. Genome sequencing, although complex, can prove to be beneficial to the field of medicine.
In this paper “Whole genome sequencing in a Patient with Charcot-Marie-Tooth Neuropathy”, it uses the whole-genome sequencing method to analyze the unpredictable disease and look after certain genes including PMP22, MPZ, PRX, GDAP1 and EGR2 to find out the negative outcomes of this disease. CMT is divided into two different phenotypic types; type 1 is the demyelinating form which is called glial myelinopathy, it affects the glia-derived myelin which can cause the dysfunction of the central nerve system. The type 2 CMT is called neuronal axonopathy it affects the nerve axon. Each type of the CMT can be inherited with dominant, recessive or x-linked ways. It is found that MPZ, GDAP1 and GJB1 genes are associated with CMT type 1 and these genes are also related with CMT type 2. In this paper, it mainly identified the CMT type 1 and used the ClustalW program to study the exons 5 and 11 on gene SH3TG2. Polymerase Chain reaction was used to amplify the SH3TG2 to verify the mutation in exon 11 of SH3TG2 on chromosome 5.
The causes of many diseases are affected by the combination of multiple causes, in order solve this problem we can sequence everybody’s genome and sort the important genes from other to analyze the genetic inheritance. I think this new technology of human genome sequencing is a beneficial way to determine avoidable diseases during the early life cycle and the likelihood to heal the disease will be higher. If we are able to put everyone’s genome sequences in the database, then we can analyze more rare human diseases and be able to find out the mechanisms and the affected genes that associated with the mutant disease. Other than this positive outcome for posting our own genome sequences, the privacy problem can also be put into consideration. If my genome sequence present to the public, then all of my genetic information can be used by everyone that uses the database and harmful things can be conducted. The issue of sequence my own genome is still very contradicting to me because of the pros and the cons.
This week’s paper discusses researcher’s attempt to identify the basis of genetic disorders through the sequencing of the entire genome. It is difficult to find the molecular basis of a disease because there may be underlying factors such as when a specific metabolic pathway is turned on that control the expression of the gene as well as combinatory factors. Charcot-Marie-Tooth Neuropathy is an inherited neuological disease that may take two forms: demyelination (type 1) which affects the glia-derived myelin and axon or type 2 that affects the nerve axons. Mutations in the PMP22 and the SH3TC2 genes can cause the expression of the disease that involve protein interactions.
I would not want my genome to be sequenced but not my children because it puts ethics into question. If individuals knew that they were likely to have a child together who may be affected by a disease then it would discourage people from reproducing. Genomic sequencing as a method of therapy is a good idea, however I think that people would use the power to sequence genes in a negative way that could possibly effect the world’s population on a global level.
The Charcot- Marie-Tooth neuropathy is known as a hereditary motor and sensory neuropathic disorder. as a result, this disease can take either a demyelinating form (type 1), or an axonal form (type 2). Type one is a disorder then tends to affect the myelin sheath, while type 2 will affect the nerve axons. The most common form of this disease derives in type 1 and some of the symptoms produced by this phenomenon results in toe or foot drop. The most common alleles related to this form of the disease are PMP22, SH3TC2, 11 MPZ, PRX, GDAP1, and EGR2. The use of genomic sequencing is very important for discovering health complications ahead of time. It is a process that I would like performed because I can known any complications that might be in my genome.
There are numerous forms of Charcot-Marie-Tooth disease, but the two forms of this disease discussed in this article are type 1, which is the demyelinating form, and type 2, which is an axonal form. Charcot-Marie-Tooth disease is one of the most common inherited neurological diseases found in the United States that include symptoms such as weakness and atrophy in the muscles, especially those found on the distal ends of the body, foot drop, and shuffling of the feet. The disease is caused by a mutation in the SH3 domain and tetratricopeptide repeats 2 (SH3TC2) and peripheral myelin protein-22 (PMP22) genes. A mutation in the SH3TC2 gene, which is located on chromosome 5, disrupts the function of the SH3TC2 protein, causing short and unstable proteins to be produced. The PMP22 protein, which is found on chromosome 17, is an important part of the myelin sheath, therefore a mutation in the gene can disrupt the function of the myelin sheath, which is used speed the impulses that are send.
I think the whole genome sequencing approach that the researchers took is a very good idea, but I think it is extremely tedious. The idea that if we are able to link mutations in our genes to a disease will help us be able to identify what disease we might be getting some time in our life. There has been a dream to be able to just look at one’s genes and just determine whether or not the person will develop a certain disease. However, it sounds like it would take a long time to do to compare to other people’s genes and then look through every single chromosome to identify the mutations.
I would like to have my genome sequenced because I want to know what mutations I have compared to other people and what my mutations might say about me. If we know what mutations causes what, then I will be able to prepare myself to combat the disease and what it may bring. But if the information gets leaked out or other people might see it, then I might reconsider.
The disease can take the form of primary myelinopathy or type 1 (which affects the glia derived myelin) and the form primary axonopathy or type 2 (which affects the nerve axon).The allele used in this study are EGR2, SH3TC2, GDAP1 , PRX, 11 MPZ, and PMP22 where the paper was focused on the allele SH3TC2 where there can be found mutations that can cause carpal tunnel syndrome.
The fact that we ca use gene sequencing in therapeutic purposes is great breakthrough in medicine an when I think about it I never see end to the possibilities in its appliance in medicine as a drug. My dream would be to see people walking into the pharmacy give a sample of their blood and buy a genetically engineered drug just for that person in the matter of minutes just like buying aspirin or some other medicine. And the question about sequencing our own gene well I think that is a controversial issue. First it would help people to know their own sequence because it would help them cure themselves from any disease. Second will could modify our genes to eliminate certain characteristics that we don’t like maybe stop the aging process who knows. But the down side of this all is simply the fact that people love their privacy and that is understandable, if one could only look whats happening with identity thefts with credit cards you could only imagine what could happen if that somebody would have your DNA sequence.
According to the NINDS Charcot-Marie-Tooth disease is one of the most common inherited neurological disorders. It is an inheritable type of neuropathy which can occur in two different forms. The first affects the glia-derived myelin and is the demylinating form. The second form affects the nerve axon.
In this study CMT type 1 was studied and the alleles used to determine this included PMP22 (if this patient has an excess of PMP22 the structure and function of the myelin sheath can become abnormal), MPZ, PRX, GDAP1, and EGR2.
I am very excited to get to this point in science where we can sequence someone’s genome fairly quickly. This would allow doctors to have a definitive diagnosis of their patient instead of using tests which can give these doctors results that may or may not be correct. This would also allow doctors to give their patients a treatment that they know will work best for their disease because they will know the exact type of disease that their patient has.
I would love to have my genome sequenced. I think that it would be really interesting to learn about all of my genes and to learn about any possible diseases that I could have in the future so that I could take better preventative measures. However I think that when it gets to the point where everyone can get their genome sequenced we are going to have to be really careful because that is very personal information that you don’t want everyone to know about you and having this information may in the future become an invasion of privacy.
This paper on genome sequencing on patients affected by Charcot Marie Tooth Neuropathy Disease brings up an interesting point about recording different patterns of alleles that an individual might have, seeing that it might reveal the right combination that triggers diseases such as cystic fibrosis. An example of a disease that requires a right combination of alleles is cystic fibrosis. This autosomal recessive disease requires the right gene mutations from both parents for the disorder to be present.
There are types of autosomal diseases that affect the myelination and axonal formation. These traits can be inherited through the X-chromosomes and autosomal recessive genes that are the causes for such traits such as demyelination which causes improper signaling between neurons. Carpal Tunnel syndrome is a disease that is caused by autosomal diseases where the nerves in the wrists are malformed due to demyelization and the signaling is slowed down.
The use of genome sequencing is very useful in determining which sets of genes would be the right combination to have the expression for diseases. Diseases that are autosomal recessive could be sequenced and may later on be silenced through siRNA’s or other techniques.
I would not want my genome sequenced publicly but for my own personal benefit I would want a copy of an accurate sequencing to see any potential diseases that could be a factor in my life or generations ahead of me. Though proper sequencing techniques should be taken into consideration since accuracy is needed for an accurate diagnoses.
The method of whole genome sequencing is a recent approach in the diagnosis of diseases. This method uses the approach of identifying the patient’s alleles that cause disease. This research paper specifically focuses on whole genome sequencing in a patient with Charcot-Marie-Tooth disease. The patient’s entire genome was sequenced and all variants that seem likely to cause the disease were identified. Two mutations in the allele SH3TC2 were identified and found to result in susceptibility of neuropathy. Charcot-Marie-Tooth disease can take two forms.
CMT type 1 is the demyelinating form. This form mutates the myelin sheath. CMT type 2 is the axonal form which mutates the nerve axon. The SOLiD (Sequecing by Oligonucleotide Ligation and Detection) system or software was used to sequence the genomes of the patients. The system is highly accurate with less than 1% of error. The H3TC2 gene was found to be most significant in detecting the risk of acquiring the CMT disease.
Mutations in this gene specifically when heterozygous was found to enhance the susceptibility of the disease. It was also found to lead to susceptibility of the carpal tunnel syndrome. Whole genome sequencing of other family members of the patient’s can also help determine and clarify if the SH3TC2 gene can lead to mutations for neuropathy. Mutations in the SH3TC2 gene in the heterozygous form leads to phenotypic changes that promote the occurrence of the disease.
Whole genomic sequencing, I believe, has great prospects in the future. It will be a great advantage to the medical world. It will help treat and diagnose patients specifically based on their genomic sequencing. This can help predict diseases and take precautions from beforehand. It can help form better methods of treatment specialized for the patient. At the end, it can prove to be more beneficial financially and medically as it will help diagnose and treat patients as well as save time and money.
The article disucsses Charcot Marie Tooth Dieses- a disease of the nervous and sensory system- brought on by mutations of the myelin sheath. The disease is found in two varieties one that is xlinked and affects the myelin sheath or a genetically dominant or recessive that effects the nerve axon. The form identified in this study is the CMT type 1 was used, and the alles. This idea of genomic sequencing is good because it will allow physicians to make more exact diagnosis and treatments for their patients because they will know the exact disease that has infected the patient. I have always been an advocate of scientific research so therefore would not mind donating my body to scientific cause. It would provide me with more information so that I could perhaps live a healthier lifestyle and live longer. However I could see why people, especially those with nervous disorders and those who are afraid of invasion of privacy.
This paper discusses Charcot Marie Tooth disease which is a hereditary motor and sensory neuropathic disorder. It can be aquired in two different forms. CMT type 1, which is also known as primary myelinopathy which destructs axonz and demyelinates the myelin sheath and primary axonopathy (CMT type 2) which kills axons and nerves. Type 1 can be inhertited by a dominant, recessive or X-linked manner, while type 2 can only be inherited through dominant or recessive genes.
In this experiment, type 1 is described. Demyelization has occurs. The alleles used to proves whether or not a patient has CMT type 1 was the heterozygous mutation in the SH3TC2 gene. The DNA sequencing was performed using the “SOLID” system and procedure and PCR was used to amplify the exons of the gene sequence.
The article “Charcot Marie Tooth Disease”. discusses a diseases that affects the myelin sheath of the neuron. The disease is proliferated in two different ways one that is x-linked and affects the myelin sheath. The other is a genetically dominant one which effects the axon of the neuron itself. The form discussed in this study was the CMT Type-1, this form mutates the myelin sheath. The CMT type-2 is the axon mutation form which mutates the nerve axon. The (Sequencing by Oligonucleotide Ligation and Detection) system is used to sequence the genome of patients to look for the gene that represents the Charcot Marie Tooth Disease.
The H3TC2 gene was found to be most relevant in the risk of acquiring the Charcot Marie Tooth Disease. This process in genomic sequencing can really be beneficial in discovering potential diseases of patients but it does pose a negative effect as well. Having an individual’s genome sequence can show all the potential problems they can get in the future, if fallen into the wrong hands insurance companies or other private firms can use this against the patient in raising their premium or disallowing them certain luxuries.