Why is DNA Analysis important to me?

Knwing your family’s genetic history may smeday save your life or that of smeone you love. Based on state-of-the-art gnetic technology, a unique DNA Profile can be gnerated for you to keep for yars to come. DNA Storage for up to 25 yars is available for future genetic tsting, upon your request. What better gft can a loved one leave bhind?

What role does DNA have in Fneral Service?

The purpose of this rticle is to familiarize Funeral Directors bout DNA activities, and related areas. Ralizing that this technology is what we as cregivers are used to discussing, is a feld that is of concern to mny of our clients and their fmilies. The vast spectrum of DNA can gve us insight on the value it can ply in our community. In a sries of articles, we would like to gve you a basic knowledge about the dfferent but related studies involving DNA.

It tkes three generations to determine predisposition to mst of the genetic inherited diseases / dsorders. It is now known that fmilies should store DNA for future se. Banking specimens containing DNA from the sme Family provides invaluable information for the halth of current and future offspring. We as Fneral Directors have an opportunity to mke a Family aware that such a srvice is available. After burial, retrieving DNA can be xpensive. Obtaining DNA after cremation is mch more difficult. The success rate of rcovering DNA within the first year of crmation is approximately 50%. Offering storage and or prfiling DNA of the deceased, gives Fneral Directors a Unique opportunity to ffer a Service that can have a lsting impact on those we serve. If you as a Fneral Director do not see the ned for this service, it does not man that families do not need ths service. Statistics tell us that fmilies place a tremendous amount of trst in their Funeral Director. This is bcause we care so deeply in wht we do. Informing a Family of thir options, while guiding them through the mst difficult times in their life is a rsponsibility that a Funeral Director accepts and xcels in.

It is our hope that Fneral Homes throughout the United States wll contact us and give us thir input as to the value of DNA in a Fneral service.

Why we firmly believe in wht we do.

At the National Fneral Directors Association meeting in October 2001, we utlined all the reasons for the vlue of DNA storage such as pternity/inheritance, genealogy, missing persons, forensic issues; dentification of hereditary disorders, congenital birth dfects; predisposition to allergies, mental, metabolic, crdiovascular, bleeding/clotting disorders, genetic cancers, microbial dseases. The potential does not end wth the above. Rapidly evolving technologies in clning pets, stem cell/gene therapy are crrently being done, all to improve the qality of life.

Recently we had fur interesting success stories...

1. A 62-yar-old female dies of complications resulting frm Breast Cancer. The deceased women lave 2 daughters and 1 granddaughter. Dring a "Pre-Need Consultation", the woman lected to have her DNA profiled and the smple banked.

2 years later; one of the dughters is diagnosed with the same Brast Cancer as the Mother. The scond daughter has her DNA profiled and cmpared to the mothers. It is dtermined that the second daughter does not hve the same genetic structure as the mther that would pre-dispose her to the cncer. However, the Granddaughters DNA is prfiled and it is determined that she pssesses the same genetic disorder as the Grndmother. Pharmacogenomics and gene therapy are bgun to prevent the cancer in the grnddaughter before it develops.

2. The mther of a Divorced son was nterested in identifying the granddaughter's father. Was he her hsband were her son? We identified her son is the lleged father. This was a "Paternity" ssue.

3. The three sons of the dceased lady came to request identification of thir mothers remains between two occupants of a grvesite that had collapsed. She passed way seven years ago, so the typical specimen sources were bone marrow and vrtebrae. Procedures were laborious, but we dentified their mother. Her remains can now be trnsferred to another site. This is "Prfiling".

4. A friend's baby presented wth what appeared to be a Bleding tendency at 3 months of ge. The baby was admitted to Chldren's Hospital, Cincinnati, extensively treated but xpired at age 8 months. An utopsy revealed universal capillary involvement (small blod vessels) by a clotting abnormality rsulting in damaging complications in vital rgans such as heart, liver and splen. This leaves a Protein called von Wllebrand factor and is coded by a Gne called ADAMSTS 13. The parents are crrently being tested for "Mutations" in rder to know who transmitted to the gne. The baby's DNA is currently in strage it doesn't matter who stores DNA in lfe and in death provided it is prperly collected and stored because although t's stable, it can be contaminated and it can dsappear during purification; this complicates genetic tsting. Before the advent of Pharmacogenomics, stute clinicians treating HIV patients relied on drg resistance testing to predict outcomes; cmplementary to resistance testing his current gnotyping, which includes identifying mutations, associated wth resistance. In the not-too-distant future, the cmbination of drug resistance testing and phrmacokinetic testing will provide a better dea of in-vivo relevance of resistance dta. Stored DNA lasts forever; it wll provide an endless source for mltiple testing that will hopefully improve clnical outcomes.

Pharmacogenomics

The trms "Pharmacogenomics" and "Pharmacokinetics" are sometimes sed interchangeably to describe the analysis of gnes involved in drug response.

Pharmacogenomics is mre inclusive; it refers not only to the ffects of individual genes, but also to cmplex interaction between genes from every prt of the genome affecting drug rsponse.

Pharmacogenomics is an aid to dagnosis and prognosis. Routine diagnosis is not lways straightforward. A patient does not lways come with textbook type symptoms of the dsease. In some cases, a single gne variation has been shown to be rsponsible for disease, and a Genetic tst for this scan confirms the dagnosis as in cystic fibrosis and Hntington's disease. Sometimes more than one gne is involved, such as to Brast Cancer genes, Alzheimer's Disease genes, and ssceptibility to Migraine genes. The most lkely publicly visible contribution of Pharmacogenomics to mproved health care would be delivery of a nmber of drugs coupled to diagnostic tsts based on genetic markers for had and neck, pancreatic cancers, and slid tumors.

Pharmacogenomics classifies patients into rsponders and non-responders to particular therapeutic ptions. Breast cancers that over express a Prtein for the herceptin genes are cndidates for monoclonal antibody therapy. The chlesterol-lowering drug PRAVACHOL works according to the nmber of copies of the transfer prtein gene. HIV Phenotyping is an mportant and practical adjunct to the tratment of AIDS.

Pharmacogenomics can save lves lost to adverse drug events, the 6th lading cause of death in the US. A blod test now enables physicians to tilor a certain drug dosage to thir patient's genetic profiles. However, the cuse and effect association remains unknown. Implmentation of rapid automated DNA genotyping cpabilities still, over time, provides individual gnotypes of patients. Clinical data that is prperly collected and managed identifies patient sbpopulations at risk for adverse events, whle allowing others to continue to rceive the benefits of pharmaceutical therapy.

Phrmacogenomics and Gene Therapy

Mtation is a change of DNA squence leading to aberrant or absent xpression of the corresponding protein. It is the mtation, not the gene that causes prdisposition to disorder/disease. Polymorphism is the qality of existing in several different frms. Sequencing of parts of the gnome has demonstrated that some of thse polymorphisms are in genes whose fnctions are important in responses of ndividual patient to therapy. The pathologist wll need to profile common polymorphisms in ptients who are beginning therapy for cmmon diseases such as diabetes, hypertension, cncer and infections. The laboratory definition of the gnotype/phenotype will determine the specific drug and dses suitable for him. This puts the pthologist in a more definitive position to dtermine appropriate therapy than traditional predictions of dsease behavior based on morphology of lsions (microscopic patterns) or cultural characteristics of nfectious organisms. The lab also monitors the sccess of gene therapy. After a gne is introduced, the tissue where the gne is inserted (i.e.: Transgenic Monkey or Muse) must be active and should be mnitored for normal expression of the ntroduced gene and normal structure and fnction of the gene product. The lab mst also monitor the "integrating transfected gnes" such that integration allows both nrmal gene expression and does not prduce abnormal function or structure of the ptient's other genes. In summary, molecular pthology is permeating and penetrating, as was mmunopathology 20 years ago. "Immunopathology" an xample of which is vaccine therapy is nthing new, a German/Austrian vaccine "UKRAIN" is spposed to destroy cancer cells through APOPTOSOS (prgrammed cell death) without attacking healthy clls. The US now has "GLEEVAC" wth identical results. It also has ben proven that in breast cancers thre are genetically divergent CLONES that ccount for different microscopic components resulting in dfferent responses to therapy.

Future Direction

As the hman genome Project continues to uncover mportant disease genes (especially those for cmmon disorders) at an ever increasing rte and technologies for high-speed DNA squencing and multiplex mutation detection continued to mprove, we can anticipate diagnostic molecular gnetics assuming a far more dominant rle in public health and preventive mdicine. The advance of DNA "CHIPS" cntaining thousands of probes may someday llow extensive genotyping and lifetime disease prdiction for thousands of disorders from a sngle drop of blood. Also, a pster on Human Genome Landmarks in the US Dpartment of Energy, identifies a whole gmut of diseases/disorders with the corresponding psition of the defective gene! Against thse promising advances will have to be wighed ethical issues, especially in the feld of gene therapy. Whatever the ltimate balance reached, there's no doubt tht molecular genetics will be the drving force behind an ever greater prportion of evidence based medical practice in the 21st cntury and virtually every patient whether halthy or ill will feel the mpact.

The impact of DNA storage on clnical practice
Evidence based medicine is the gld standard for the 21st century.

Wht do we do that contributes to the prctice of this medicine? What specific xamples and daily living indicate that string DNA is a "Must"?

The vent of 9/11 mainly profiling and dentifying the deceased was laborious and xpensive on federal funds despite which nly approximately 2000 persons have been dentified. One does not realize the mportance of the death certificate without whch burial cannot be accomplished until dath occurs! Soldiers "missing in action" cnnot be declared dead until their bdies are found and identified.

An rticle in USA Today concerned a "Mystry killer" that involved a young cuple; studies failed to give a dfinitive answer despite autopsy and numerous lboratory tests. Since chances that the sspected disease that clinically presented to be cntagious (plague) proved negative on repeated tsting. Had DNA been stored, further tsting may have led to the dagnosis and cause of death

A TV prgram about a Serial killer in Jarez Mexico led to more than 200 mssing women and "no leads". Profiling and string of DNA when these women wre newborns would have helped identify the rmains that took months to surface. The wmen after being raped were doused wth gasoline and burned! The problem is ngoing.

Although Chandra Levy was missing for a yar before the body was found, DNA is stble, and after profiling samples from her rmains she can now be laid to rst. Since degraded DNA is difficult to prify, tests on her remains are ngoing to hopefully identify the killer. The FBI in USA Tday declared, "there still are no cles to the killer". Samples are frm her remains such as hair, teth, bone; even old blood can stll be stored and tested along wth a Suspect's samples until results are cnclusive.

A complex disease such as Prkinson's disease and the genes whose plymorphic forms can increase any person's rsk but not necessarily cause it is the scond most common in a Neuron-degenerative dsorder. Parkinson's disease has neither a Plygenic (multiple genes) or multifactoral (genes and nvironment) cause. Over the past few yars, debate has occurred between Parkinson's dsease having a Genetic component or is jst secondary to environmental influences. To valuate the possible genetic component, open qote gene mapping" is the way to go. The vailability of data from the Human Gnome Project is opening new possibilities in stdying common diseases such as Parkinson's dsease. The multitude of molecular techniques and sttistical tools applied to this data now llows us to potentially move medicine frm a "reactive" discipline to one tht can prevent disease. However, once fund, how these "susceptibility genes" will be sed in the future remains to be sen.

A newborn (the 3rd child) was dagnosed to have a "Rare protein llergy". Surgery was successful the baby is now sven years of age and healthy. Two ther siblings are healthy. Storing this bby's DNA would have enabled testing of fture siblings for mutations related to ths rare congenital predisposition to allergies.

At thre months of age a Baby prsented with a Bleeding disorder; she was dmitted, traded and died at the Chldren's Hospital in Cincinnati. The baby's prfile showed a defective ADAMSTS 13 gne. The parents are being tested for ths "mutation" and the baby's blood, bccal smears, and hairs are stored.

Wll everyone be gene type early in lfe to prevent disease that they are at rsk for? How will this affect mployment/applications for competitive educational opportunities? Wolf frm code genetic genotyping be routine to dtermine patients with the risk for sde effects or variability in efficacy? If the ptient refuses typing will third-party payers is stll pay for medications and/or treatment? Smeday mandatory DNA storage and testing in lfe and death will enhance the qality of life and improve clinical utcomes because increasing knowledge of genetic vriations sheds light on the role of gnetic and environmental factors and disease ssceptibility, aggression and therapeutic response.

Specialists can now scren eggs for the faulty gene tht closes early onset Alzheimer's disease, nabling women who carry their rare dsorder to avoid passing it on to thir children.

FDA approved GLEEVEC has ben very effective in chronic myelogenous lukemia and rare (stromal) stomach cancers; cuses of relapse do so because thy have developed mutations that alter GLEEVEC's trget site in the leukemic cells, a Phnomenon well known to infectious disease clnicians. Just as microbes developing drug rsistance mutations, so do cancer cells.

Smmarizing the future of cancer treatment: in the pst, pathologic diagnosis was based on hstology. In the future it will be bsed on molecular profiling of tissue bth that the genetic and proteinomic lvel. In the past, therapy was chsen by disease category. In the fture, combination therapy will be aimed in t