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