Grandparents Use DNA Analysis to Prevent and Treat Inherited Diseases for Future Generations
By Scott Nizborski
Why is DNA Analysis important to me?
Knowing your family’s genetic history may someday save your life or that of someone you love. Based on state-of-the-art genetic technology, a unique DNA Profile can be generated for you to keep for years to come. DNA Storage for up to 25 years is available for future genetic testing, upon your request. What better gift can a loved one leave behind?
What role does DNA have in Funeral Service?
The purpose of this article is to familiarize Funeral Directors about DNA activities, and related areas. Realizing that this technology is what we as caregivers are used to discussing, is a field that is of concern to many of our clients and their families. The vast spectrum of DNA can give us insight on the value it can play in our community. In a series of articles, we would like to give you a basic knowledge about the different but related studies involving DNA.
It takes three generations to determine predisposition to most of the genetic inherited diseases / disorders. It is now known that families should store DNA for future use. Banking specimens containing DNA from the same Family provides invaluable information for the health of current and future offspring. We as Funeral Directors have an opportunity to make a Family aware that such a service is available. After burial, retrieving DNA can be expensive. Obtaining DNA after cremation is much more difficult. The success rate of recovering DNA within the first year of cremation is approximately 50%. Offering storage and or profiling DNA of the deceased, gives Funeral Directors a Unique opportunity to offer a Service that can have a lasting impact on those we serve. If you as a Funeral Director do not see the need for this service, it does not mean that families do not need this service. Statistics tell us that families place a tremendous amount of trust in their Funeral Director. This is because we care so deeply in what we do. Informing a Family of their options, while guiding them through the most difficult times in their life is a responsibility that a Funeral Director accepts and excels in.
It is our hope that Funeral Homes throughout the United States will contact us and give us their input as to the value of DNA in a Funeral service.
Why we firmly believe in what we do.
At the National Funeral Directors Association meeting in October 2001, we outlined all the reasons for the value of DNA storage such as paternity/inheritance, genealogy, missing persons, forensic issues; identification of hereditary disorders, congenital birth defects; predisposition to allergies, mental, metabolic, cardiovascular, bleeding/clotting disorders, genetic cancers, microbial diseases. The potential does not end with the above. Rapidly evolving technologies in cloning pets, stem cell/gene therapy are currently being done, all to improve the quality of life.
Recently we had four interesting success stories...
1. A 62-year-old female dies of complications resulting from Breast Cancer. The deceased women leave 2 daughters and 1 granddaughter. During a "Pre-Need Consultation", the woman elected to have her DNA profiled and the sample banked.
2 years later; one of the daughters is diagnosed with the same Breast Cancer as the Mother. The second daughter has her DNA profiled and compared to the mothers. It is determined that the second daughter does not have the same genetic structure as the mother that would pre-dispose her to the cancer. However, the Granddaughters DNA is profiled and it is determined that she possesses the same genetic disorder as the Grandmother. Pharmacogenomics and gene therapy are begun to prevent the cancer in the granddaughter before it develops.
2. The mother of a Divorced son was interested in identifying the granddaughter's father. Was he her husband were her son? We identified her son is the alleged father. This was a "Paternity" issue.
3. The three sons of the deceased lady came to request identification of their mothers remains between two occupants of a gravesite that had collapsed. She passed away seven years ago, so the atypical specimen sources were bone marrow and vertebrae. Procedures were laborious, but we identified their mother. Her remains can now be transferred to another site. This is "Profiling".
4. A friend's baby presented with what appeared to be a Bleeding tendency at 3 months of age. The baby was admitted to Children's Hospital, Cincinnati, extensively treated but expired at age 8 months. An autopsy revealed universal capillary involvement (small blood vessels) by a clotting abnormality resulting in damaging complications in vital organs such as heart, liver and spleen. This leaves a Protein called von Willebrand factor and is coded by a Gene called ADAMSTS 13. The parents are currently being tested for "Mutations" in order to know who transmitted to the gene. The baby's DNA is currently in storage it doesn't matter who stores DNA in life and in death provided it is properly collected and stored because although it's stable, it can be contaminated and it can disappear during purification; this complicates genetic testing. Before the advent of Pharmacogenomics, astute clinicians treating HIV patients relied on drug resistance testing to predict outcomes; complementary to resistance testing his current genotyping, which includes identifying mutations, associated with resistance. In the not-too-distant future, the combination of drug resistance testing and pharmacokinetic testing will provide a better idea of in-vivo relevance of resistance data. Stored DNA lasts forever; it will provide an endless source for multiple testing that will hopefully improve clinical outcomes.
The terms "Pharmacogenomics" and "Pharmacokinetics" are sometimes used interchangeably to describe the analysis of genes involved in drug response.
Pharmacogenomics is more inclusive; it refers not only to the effects of individual genes, but also to complex interaction between genes from every part of the genome affecting drug response.
Pharmacogenomics is an aid to diagnosis and prognosis. Routine diagnosis is not always straightforward. A patient does not always come with textbook type symptoms of the disease. In some cases, a single gene variation has been shown to be responsible for disease, and a Genetic test for this scan confirms the diagnosis as in cystic fibrosis and Huntington's disease. Sometimes more than one gene is involved, such as to Breast Cancer genes, Alzheimer's Disease genes, and susceptibility to Migraine genes. The most likely publicly visible contribution of Pharmacogenomics to improved health care would be delivery of a number of drugs coupled to diagnostic tests based on genetic markers for head and neck, pancreatic cancers, and solid tumors.
Pharmacogenomics classifies patients into responders and non-responders to particular therapeutic options. Breast cancers that over express a Protein for the herceptin genes are candidates for monoclonal antibody therapy. The cholesterol-lowering drug PRAVACHOL works according to the number of copies of the transfer protein gene. HIV Phenotyping is an important and practical adjunct to the treatment of AIDS.
Pharmacogenomics can save lives lost to adverse drug events, the 6th leading cause of death in the US. A blood test now enables physicians to tailor a certain drug dosage to their patient's genetic profiles. However, the cause and effect association remains unknown. Implementation of rapid automated DNA genotyping capabilities still, over time, provides individual genotypes of patients. Clinical data that is properly collected and managed identifies patient subpopulations at risk for adverse events, while allowing others to continue to receive the benefits of pharmaceutical therapy.
Pharmacogenomics and Gene Therapy
Mutation is a change of DNA sequence leading to aberrant or absent expression of the corresponding protein. It is the mutation, not the gene that causes predisposition to disorder/disease. Polymorphism is the quality of existing in several different forms. Sequencing of parts of the genome has demonstrated that some of these polymorphisms are in genes whose functions are important in responses of individual patient to therapy. The pathologist will need to profile common polymorphisms in patients who are beginning therapy for common diseases such as diabetes, hypertension, cancer and infections. The laboratory definition of the genotype/phenotype will determine the specific drug and doses suitable for him. This puts the pathologist in a more definitive position to determine appropriate therapy than traditional predictions of disease behavior based on morphology of lesions (microscopic patterns) or cultural characteristics of infectious organisms. The lab also monitors the success of gene therapy. After a gene is introduced, the tissue where the gene is inserted (i.e.: Transgenic Monkey or Mouse) must be active and should be monitored for normal expression of the introduced gene and normal structure and function of the gene product. The lab must also monitor the "integrating transfected genes" such that integration allows both normal gene expression and does not produce abnormal function or structure of the patient's other genes. In summary, molecular pathology is permeating and penetrating, as was immunopathology 20 years ago. "Immunopathology" an example of which is vaccine therapy is nothing new, a German/Austrian vaccine "UKRAIN" is supposed to destroy cancer cells through APOPTOSOS (programmed cell death) without attacking healthy cells. The US now has "GLEEVAC" with identical results. It also has been proven that in breast cancers there are genetically divergent CLONES that account for different microscopic components resulting in different responses to therapy.
As the human genome Project continues to uncover important disease genes (especially those for common disorders) at an ever increasing rate and technologies for high-speed DNA sequencing and multiplex mutation detection continued to improve, we can anticipate diagnostic molecular genetics assuming a far more dominant role in public health and preventive medicine. The advance of DNA "CHIPS" containing thousands of probes may someday allow extensive genotyping and lifetime disease prediction for thousands of disorders from a single drop of blood. Also, a poster on Human Genome Landmarks in the US Department of Energy, identifies a whole gamut of diseases/disorders with the corresponding position of the defective gene! Against these promising advances will have to be weighed ethical issues, especially in the field of gene therapy. Whatever the ultimate balance reached, there's no doubt that molecular genetics will be the driving force behind an ever greater proportion of evidence based medical practice in the 21st century and virtually every patient whether healthy or ill will feel the impact.
The impact of DNA storage on clinical practice
Evidence based medicine is the gold standard for the 21st century.
What do we do that contributes to the practice of this medicine? What specific examples and daily living indicate that storing DNA is a "Must"?
The event of 9/11 mainly profiling and identifying the deceased was laborious and expensive on federal funds despite which only approximately 2000 persons have been identified. One does not realize the importance of the death certificate without which burial cannot be accomplished until death occurs! Soldiers "missing in action" cannot be declared dead until their bodies are found and identified.
An article in USA Today concerned a "Mystery killer" that involved a young couple; studies failed to give a definitive answer despite autopsy and numerous laboratory tests. Since chances that the suspected disease that clinically presented to be contagious (plague) proved negative on repeated testing. Had DNA been stored, further testing may have led to the diagnosis and cause of death
A TV program about a Serial killer in Juarez Mexico led to more than 200 missing women and "no leads". Profiling and storing of DNA when these women were newborns would have helped identify the remains that took months to surface. The women after being raped were doused with gasoline and burned! The problem is ongoing.
Although Chandra Levy was missing for a year before the body was found, DNA is stable, and after profiling samples from her remains she can now be laid to rest. Since degraded DNA is difficult to purify, tests on her remains are ongoing to hopefully identify the killer. The FBI in USA Today declared, "there still are no clues to the killer". Samples are from her remains such as hair, teeth, bone; even old blood can still be stored and tested along with a Suspect's samples until results are conclusive.
A complex disease such as Parkinson's disease and the genes whose polymorphic forms can increase any person's risk but not necessarily cause it is the second most common in a Neuron-degenerative disorder. Parkinson's disease has neither a Polygenic (multiple genes) or multifactoral (genes and environment) cause. Over the past few years, debate has occurred between Parkinson's disease having a Genetic component or is just secondary to environmental influences. To evaluate the possible genetic component, open quote gene mapping" is the way to go. The availability of data from the Human Genome Project is opening new possibilities in studying common diseases such as Parkinson's disease. The multitude of molecular techniques and statistical tools applied to this data now allows us to potentially move medicine from a "reactive" discipline to one that can prevent disease. However, once found, how these "susceptibility genes" will be used in the future remains to be seen.
A newborn (the 3rd child) was diagnosed to have a "Rare protein allergy". Surgery was successful the baby is now seven years of age and healthy. Two other siblings are healthy. Storing this baby's DNA would have enabled testing of future siblings for mutations related to this rare congenital predisposition to allergies.
At three months of age a Baby presented with a Bleeding disorder; she was admitted, traded and died at the Children's Hospital in Cincinnati. The baby's profile showed a defective ADAMSTS 13 gene. The parents are being tested for this "mutation" and the baby's blood, buccal smears, and hairs are stored.
Will everyone be gene type early in life to prevent disease that they are at risk for? How will this affect employment/applications for competitive educational opportunities? Wolf farm code genetic genotyping be routine to determine patients with the risk for side effects or variability in efficacy? If the patient refuses typing will third-party payers is still pay for medications and/or treatment? Someday mandatory DNA storage and testing in life and death will enhance the quality of life and improve clinical outcomes because increasing knowledge of genetic variations sheds light on the role of genetic and environmental factors and disease susceptibility, aggression and therapeutic response.
Specialists can now screen eggs for the faulty gene that closes early onset Alzheimer's disease, enabling women who carry their rare disorder to avoid passing it on to their children.
FDA approved GLEEVEC has been very effective in chronic myelogenous leukemia and rare (stromal) stomach cancers; causes of relapse do so because they have developed mutations that alter GLEEVEC's target site in the leukemic cells, a Phenomenon well known to infectious disease clinicians. Just as microbes developing drug resistance mutations, so do cancer cells.
Summarizing the future of cancer treatment: in the past, pathologic diagnosis was based on histology. In the future it will be based on molecular profiling of tissue both that the genetic and proteinomic level. In the past, therapy was chosen by disease category. In the future, combination therapy will be aimed in tailored to individual patient profiles or classes of profiles. Select, monitor, and reevaluate.. that's hope for the future!
Scott Nizborski is the President and Owner of LabEx, Inc.
LabEx is an authorized represetative for DNA Analysis providing DNA Profiling and Storage Services focused on the Funeral Pre-Need business.
Article Source: http://EzineArticles.com/?expert=Scott_Nizborski