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Genetic Testing

bedouin womanHelping the Desert Bedouins with Genetic Testing

Last year I attended a presentation by Dr. Ohad Birk of Ben Gurion University about the value of genetic testing in the desert Bedouin people in Israel.  Apparently the Bedouins have a high rate of close inter-marriage resulting in mutations matching up in the offspring leading to devastating rare genetic diseases. Obviously this carried a heavy emotional price.  Since Bedouins are Israeli citizens and entitled to universal health care, this also carries increased health care costs for the taxpayers.  Dr Birk explained how his program of testing and counseling saves tens of millions of dollars by preventing these genetic diseases.(11)(12)(13)

Image at Right: Bedouin Woman in Jerusalem 1898 Courtesy of the United States Library of Congress's Prints and Photographs Division

It is amazing to think about it, but a number of online DNA testing companies offer the same testing services provided by Dr. Ohad Birk: DNA Direct23andMe, DeCodeMe, Navigenics,  Knome, and MDL.

DNA Direct is one of these online genetic testing services offering a reasonable list of tests. Each test actually corresponds with a known risk for disease or clinical abnormality.(7)  Before you go online for your testing, however, you might want to discuss this with your doctor who can order the same genetic test through Quest or LabCorp at your next routine blood draw. 

If Anonymity is an Issue

Rather than going through their doctor, many people choose anonymous online genetic testing  in order to maintain confidentiality of test results from the insurance companies. A positive result may have a negative impact on future health insurability, etc.

The senate passed an anti-discrimination bill April 2008 to prevent health insurance companies from canceling coverage based on results of genetic testing. However, I remain skeptical, and doubtful that this offers any real protection.

Beware that many of the genetic tests offered online are not ready for clinical use, and may be premature.  However, DNA Direct has a reasonable list which are described below.  This is a rapidly  evolving field.
List of Online Tests Offered by DNA Direct:(7)

Alpha-1 Antitrypsin Deficiency, Asthma and Lung Disease

Alpha-1 Antitrypsin is a protein in the lung tissue, and deficiency leads to a tissue breakdown in the lung causing pulmonary emphysema.(1
Alpha-1 Carrier Status

About 1 in every 10-30  Americans are Alpha-1 carriers. While carriers are usually asymptomatic,  they may be more susceptible to lung injury from toxins such as cigarette smoke, or susceptible to liver injury from toxins such as acetaminophen (tylenol).  Preventive measures include avoidance of lung and liver toxins.  Most Alpha-1 carriers have enough protein production to remain disease free.

Image at left: structure of alpha-1-anti-trypsin protein courtesy of wikipedia.

Severe Alpha-1 Deficiency

An estimated 100,000 people in the U.S. (1 in 2500) and a similar number in Europe have severe Alpha-1 antitrypsin deficiency.  Since the symptoms of asthma are common in the general population, Alpha-1 patients are most often misdiagnosed as having asthma.   On average it takes seven years and three doctors to make the correct diagnosis of alpha-1 which causes 3 percent of all cases of emphysema, and COPD (chronic obstructive pulmonary diseases) in the U.S. 

There is a treatment with Prolastin (Bayer), which is purified alpha-1-anti-trypsin protein,  is available.(8)  If the patient has asthma, it might be reasonable to test for Alpha-1 in order to make the diagnosis. 

Ancestry and Ethnicity Test Panel 

Ashkenazi Jewish Carrier Screening Panel (in Alphabetical Order)

Left Image: Ahkenazi Shofar Courtesy of Wikipedia.

Bloom Syndrome: The carrier frequency in individuals of Eastern European ancestry is about 1/100. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child.

Bloom syndrome is caused by mutations in the BLM gene responsible for the DNA helicase, an enzyme that unwinds the two spiral strands of a DNA molecule so that they can be copied.  The chromosome copying mechanism is faulty causing a high risk for early cancer in affected individuals.

Canavan Disease: One in 40 individuals of Ashkenazi Jewish ancestry is a carrier of Canavan disease. 

Canavan disease is a leukodystrophies, characterized by degeneration of myelin, which is the fatty covering that insulates nerve fibers in the brain causing abnormal neurological development, and poor survival of the affected child.  The American College of Medical Genetics (ACMG) and the American College of Obstetrics and Gynecology (ACOG) recommend Canavan carrier screening for all Ashkenazi Jewish individuals.

Cystic Fibrosis: One in 25 Ashkenazi Jewish individuals are CF carriers. The American College of Obstetrics and Gynecology (ACOG) recommends that all couples who are pregnant or planning a pregnancy be offered CF carrier screening.

Familial Dysautonomia: Autosomal recessive, and almost exclusively in Ashkenazi Jews.  Both parents must be carriers in order for the child to be affected. The carrier frequency in Jewish individuals of Eastern European (Ashkenazi) ancestry is about 1/30, while the carrier frequency in non-Jewish individuals is about 1/3000. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child.  Genetic counseling and genetic testing is recommended for families who may be carriers of familial dysautonomia.(2)

Fanconi Anemia: One in 89 Ashkenazi Jewish individuals is a carrier of Fanconi anemia Type C.

Gaucher Disease: About 1 in 100 people in the U.S. population are carriers, and about 1 in 15 Ashkenazi Jews are carriers for Gaucher's disease. 

Gaucher's disease is the most common of the storage diseases caused by a deficiency of the lysosomal enzyme glucocerebrosidase, which breaks down glucocebrosides, found in red and white blood cell membranes. This leads to an accumulation a fatty substance in various RE and filtering organs such as the spleen, liver, kidneys, lungs, as well as brain and bone marrow.  Symptoms may include hepatosplenomegaly, skeletal disorders and severe neurologic abnormalities.

There is an effective  treatment with enzyme replacement with recombinant glucocerebrosidase given intravenously every two weeks which can dramatically reverse the symptoms.  However, this treatment with Cerezyme costs $500,000 annually for the lifetime of the patient.

Mucolipidosis IV: About 1 in 100 Ashkenazi Jewish individuals is a carrier. Mucolipidosis is a neurodegenerative lysosomal storage disorder.  Symptoms include agenesis of the corpus callosum, neurological and opthalmic abnormalities.

Niemann-Pick Disease: Caused by the deficiency of the enzyme, acid sphingomyelinase, leading to accumulation of sphingomyelin in the liver and spleen (hepatosplenomegaly), progressive deterioration of the nervous system, and poor survival in the severe form of the genetic disease.  One in 90 people with Ashkenazi Jewish ancestry is a carrier of Niemann-Pick Type A (severe) or Type B (less severe form).(3)

Tay-Sachs Disease: One in 30 people with Ashkenazi Jewish ancestry is a carrier of Tay-Sachs disease. Because of the high carrier rate, the American College of Medical Genetics (ACMG) and the American College of Obstetrics and Gynecology (ACOG) recommend screening for Ashkenazi Jewish individuals. ACOG recommends that couples in which only one member is Ashkenazi Jewish also consider carrier testing for Tay-Sachs disease.

Tay-Sachs disease is a severe progressive disorder that causes deterioration of the central nervous system, resulting in poor muscle tone, loss of motor skills, seizures, blindness, and difficulties with swallowing and breathing. On eye exam, people with Tay-Sachs disease have an unusual appearance to the retina, known as a cherry-red spot. Children born with Tay-Sachs disease appear normal at birth, however symptoms begin as early as 3 months of age and death usually occurs by age 4. There is no cure for Tay-Sachs disease.

Blood Clotting Disorders (Factor V Leiden, Prothrombin)

This genetic test looks for a mutation in two genes which increase risk for blood clots, factor V Leiden, and prothrombin mutation.  These lead to increase risk for deep venous thrombosis in the calf veins, and associated pulmonary embolism.  Once identified as a carrier, one can take precautions to prevent deep venous thrombosis.

Factor V Leiden

Factor V Leiden is found in 1 in 20 Caucasians, and is rare in Hispanic Americans, and African Americans.  A mutation here increases the risk of blood clot formation.

Factor V Leiden is also found in 10% to 20% of people of all ages with first-time venous blood clots, 40% of people younger than 50 with first-time venous clots, and 60% of pregnant women with venous thrombosis.

Factor V Leiden has been associated with an increased risk of recurrent pregnancy loss, severe  preëclampsia, fetal growth retardation, stillbirth, and placental problems (infarction and abruption).

Prothrombin (Factor II) G2021A

Similar to Factor V Leiden, the Prothrombin mutation is found in about 1% to 2% of the Caucasian population. It is rare in the African and Asian populations.  Prothrombin G2021A is found in 6% to 8% of people with a first-time venous clot, has been associated with myocardial infarction (heart attack) in young women and cerebral (brain) venous thrombosis. 

Breast & Ovarian Cancer Risk-BRCA1 and BRCA2

Hereditary cancer has general features that include: Cancer diagnosed at a young age (earlier than 50 years old), multiple primary cancers in the same person, a combination of certain cancers in a family, such as breast and ovarian or colon and uterine.

Key features in history suggesting hereditary breast and ovarian cancer are:

1) Breast cancer before age 50
2) Ovarian cancer at any age
3) Breast cancer in both breasts
4) Breast cancer and ovarian cancer in the same person.
5) Male breast cancer
6) Ashkenazi Jewish ancestry 

Genetic testing for breast and ovarian cancer deals with two extremely large genes — called BRCA1 and BRCA2 — and hundreds of possible mutations.

Ashkenazi Jews, however, present a simplified pattern, mostly involving one of three specific BRCA mutations. This test, called multisite analysis, looks exclusively for three mutations in the BRCA1 and BRCA2.

Colon Cancer Screening. The DNA Stool Test  examines a stool sample for 23 DNA markers that are associated with colorectal cancer and pre-cancerous polyps.

Cystic Fibrosis- CFTR gene.

 Cystic fibrosis (CF) is a disease of thick mucous affecting lungs, liver, and pancreas, charaterized by repeatd and frequent lung infections, digestive problems with decreased pancreatic enzyme production.  These in turn cause growth retardation and deficiency in fat-soluble vitamins A, D, and E.  The diagnosis of CF can be made with sweat test.  There is no cure for CF.  Life expectancy is shortened with most succumbing to lung infection in their 20s and 30s. CF is a common genetic disorder with  5% of people of European descent carriers for CF with one gene affected.

Above Image: Cystic fibrosis breathing treatment courtesy of Wikipedia

CF is caused by a mutation in CFTR gene, making an abnormal chloride ion channel which makes sweat, digestive juices, and mucus. Professional medical groups including the NIH, ACUG, and ACOG recommend that CF carrier screening be offered to all couples who are planning a pregnancy or are currently pregnant.

Drug Response Testing

Three genes are responsible for enzymes that metabolize medications.  Mutations in these genes can produce '"poor metabolizers" who nee lower doses of medication to avoid overdose.  This information is useful in personalizing drug treatment.


Hemochromatosis (iron accumulation) is the most common genetic disorder in Caucasians, with an estimated prevalence of 1/4 to 1/2 per cent having both genes affected (homozygotes) and 10-12 per cent carriers (one gene).

Iron accumulation of heochromatosis is an example of a common genetic disorder whiich has a curative treatment if diagnosed early.  This treatment is bleeding or phlebotomy which removes the iron from the body. Those 18th century bleeding treatments weren't so ridiculous after all.  

The disease causes iron accumulation in the liver, adrenals, heart and pancreas, causing cirrhosis, adrenal insufficiency, heart failure and diabetes. The cirrhosis is associated with increased risk of liver cancer.  The more common clinical presentations are malaise, liver cirrhosis, insulin resistance, diabetes mellitus type 2 (due to pancreatic damage), erectile dysfunction, decreased libido, congestive heart failure, arrhythmias, arthritis, adrenal insufficiency, deafness, parkinsonian symptoms, hypothyroidism, a darkish colour to the skin (Diabetes bronze), etc.
Males are usually diagnosed after their forties and fifties, and women several decade later owing to regular iron loss through menstruation (which ceases in menopause). Many patients who have the full blown genetic mutation (homozygous) may be asymptomatic, or have minimal symptoms, showing only an elevated ferritin or saturation.  Diagnosis is commonly made with elevated LFT's (liver enzymes), elevated ferritin, and increased iron binding saturation. DNA testing for two mutations in the HFE gene, C282Y and H63D, makes the diagnosis (available at Quest and Labcorp). (9)(10)

Imaging features: The increased iron stores in the liver and pancreas result in characteristic findings on unenhanced CT and a decreased signal intensity at MR imaging. 

  Routine screening of population for haemochromatosis is generally not done, since serum ferritin is a more practical and less expensive marker. Serum ferritin above 1000 ng/mL suggests iron overload.

Left image: ferritin protein structure courtesy of wikipedia
Early diagnosis allows prompt curative treatment with phlebotomy (discarded blood donation) which removes iron from the body.  Treatment is usually started with ferritin above 200-300 mg/L.

Warfarin Response Testing

 Warfarin response testing looks at two genes, called CYP2C9 and VKORC1 which determine our response to coumadin.  CYP2C9 is a gene involved in warfarin metabolism.  CYP2C9 variants have reduced metabolism and generally require lower warfarin doses. VKORC1 is involved in vitamin K epoxide reductase, or VKOR which makes the blood-clotting proteins.  Warfarin works by reducing this enzyme's activity.  A common VKORC1 gene variant (called -1639G>A) also reduces the enzyme’s activity.  If one has  low enzyme levels to start with, an average warfarin dose may be too much, and cause excessive bleeding.

Above image:CYP2C9 protein courtesy of wikipedia

Cardiovascular Disease


The most common inherited cardiovascular diseases which have genetic testing are:

Hypertrophic cardiomyopathy (HCM) is most common affecting 0.1 per cent of the population.  It causes muscle thickening in the ventricles of the heart.  Many are asymptomatic, however, symptoms may include shortness of breath, tiredness, chest pain, fainting or near-fainting, or heart palpitations.

Dilated Cardiomyopathy (DCM): This causes the heart to enlarge, weaken, and reduce pumping ability causing heart failure, fatigue, shortness of breath, and fluid retention with swelling of the ankles and feet.

Inherited Arrhythmias are abnormal heart beats or rhythms caused by gene mutations causing  faintness, dizziness, and heart palpitations.

Marfan Syndrome is a genetic disorder of the connective tissue involving the eyes, skin, bone, and heart producing sympoms such as nearsightedness or arrhythmias.
Familial Aortic Aneurysm (FAA) causes the aorta starts to stretch and bulge called an aneurysm. The aorta is a large blood vessel that carries blood from the heart to the rest of the body. Symptoms may include general abdominal pain or discomfort, or pain in the chest or lower back.

Coronary Artery Disease - Heart Disease

See this article:
Genetics of Heart Disease - Inheritance Patterns - Review Article

So far, there are 250 genes involved in heart disease producing a blended effect.  This makes things complicated. A person may have some mutations that increase risk and other mutations  decrease risk. On average, a person's risk level is approximately midway between those of the parents.

LDL Metabolism,  LDL Receptor. 1985, Michael Brown and Joseph Goldstein  Nobel prize for gene for familial hypercholesterolemia, or FH.  FH is inherited in a dominant manner. 

Apolipoprotein E.  More than 30 mutant forms of apo E. the e4 version of the gene tend to have higher cholesterol levels than the general population, but levels in people with the e2 version are significantly lower. The apo E gene has also been implicated in Alzheimer's disease. 

Apolipoprotein(a). Apo(a) combines with LDL to form Lp(a) often found as a part of plaques . High Lp(a) levels (over 30 mg/dL) indicates higher risk of developing CAD. Lp(a) levels may be reduced with the vitamin niacin, or by hormone replacement therapy in postmenopausal women.
Homocysteine Metabolism, (hyperhomocystinemia) is known to be a risk factor for CAD.  In the US, about one in eight people have a mutation for MTHFR, with elevation in homocysteine, treatable with folate, B6 B12 vitamins.

Apolipoprotein A1 is a protein found in the HDL particle, the  "good cholesterol". Some mutations  in the apo A1 gene result are bad causing early heart attacks, and strokes. 

A particular mutation in Apo A1 found in some residents of Milan, Italy, called the "Milano" mutation results in very low levels of HDL. Although these people have very low levels of HDL, they also have a low incidence of Heart Disease.

Genetic Testing for CAH - Coronary Artery Disease

In general, tests for specific genetic mutations are not performed in CAD. Indirect tests are much easier and less expensive.  For example, blood homocysteine levels are useful.  If elevated, treatment is B6 B12 and folate vitamins.

Celiac Disease

EnteroLab offers a home test kit for both antibodies and genetic testing for celiac disease.  This is a test kit sent to the home, and a stool sample is provided and mailed back to the lab.  One of my patients had spent years going to multiple doctors with severe neurapathies and various other symptons of celiac disease and had been told all her tests were negative.  Her EnteroLab test was positive and she has improved dramatically on a gluten free diet.


In conclusion, whether or not to do genetic testing can be a complicated question.  Sometimes it is very useful, sometimes not.  Sometimes it may lead to difficult moral and ethical questions when applied to the unborn child. 

In some cases gene testing is useful for the individual to confirm a diagnosis, such as alpha 1 anti-trypsin deficiency in the asthmatic patient, or to confirm hemochromatosis in the patient with elevated ferritin. Gene testing may be useful to predict future disease risk, such as cancer risk with BRCA genes, so that preventive measures can be taken. 

Genetic testing may be useful for family planning.  When parents have knowledge of their carrier status, they can take precautions to prevent a severe a genetic disease in the unborn child.  Obviously there are ethical issues to be considered in regards to eugenics which we have not touched upon. This is the subject for a later report.

In some cases, genetic testing is either redundant or simply not useful.  For example, there is no reason to do genetic testing for type two diabetes when the fasting blood sugar is already abnormal and is a more useful marker.  There is no reason to do genetic testing for famiial hypercholesterolemia when the routine lipid panel provides this information.  Likewise, there is no reason to do genetic testing to determine eye color or hair color when a simple examination provides this information.

Genetic testing a rapidly evolving field, and new information is coming online all the time.

Very soon, the cost for routine whole human genome sequencing will become cheaper, and some day will be offered during routine clinical testing along with the CBC, blood count and chemistry panel.  Also, we will very soon have a greater understanding of gene variation and disease risk, which will hopefully allow intelligent and useful interpretation of the routine clinical sequencing of the entire human genome.  As of May 2008, we are not quite there yet.

Jeffrey Dach MD
7450 Griffin Rd Suite 180/190
Davie, FL 33314
Phone: 954-792-4663


Alpha 1 anti trypsin wikipedia

Familial Dysautonomia

Niemann Pick




Common Genetic Disorders LAbcorp

DNA Direct Web Site

Information on Prolastin treatment for alpha -1-antitryin deficiency
alpha1-Proteinase Inhibitor (Human), Prolastin is a sterile, stable, lyophilized preparation of purified human Alpha1-Proteinase Inhibitor (alpha1-PI) also known as alpha1-antitrypsin. Prolastin is intended for use in therapy of congenital alpha1-antitrypsin deficiency.

Quet NEwletter dealing with hemochromatosis. Approximately 85-90% of patients with typical clinical features of HFHC are homozygous for the C282Y mutation. However, only 40-50% of homozygous patients demonstrate clinical disease.


Quest LAB DNA test for hemochromatosis Chantilly Lab
Code: 10249 Hereditary Hemochromatosis DNA Mutation Analysis [35079X]
This assay detects the two mutations in the HFE gene, C282Y (NM_000410.2: c.845G>A) and H63D (NM_000410.2: c.187C>G), that are commonly associated with HH. The mutations are detected by multiplex-polymerase chain reaction (PCR) amplification, followed by digestion of the amplification products with the restriction enzymes RsaI and NlaIII, for the detection of the C282Y and H63D mutations respectively. Fluorescent-labeled restriction fragments are detected by capillary electrophoresis. Code: 141661 Hereditary Hemochromatosis DNA MutationAnalysis,NY [36193X]


Helping Israeli Bedouin by identifying mutant genes By David Margolis   July 04, 2004
The Negev Bedouin are a relatively isolated population, and they have a very high proportion of consanguineous marriages, with some two-thirds of individuals married to first or second cousins. As an unfortunate consequence, the Bedouin show a high rate of genetically-determined neurological, skeletal, eye, cardiac, gastro-intestinal, skin and eye diseases. There's even "hereditary infertility" - not a contradiction in terms, explains Birk, acting director of the Genetics Institute at Soroka Medical Center in Beersheva and head of the Ben-Gurion University's Human Molecular Genetics Lab, but a matter of statistics, since if both parents carry the defective gene, perhaps a quarter of their children will suffer the defect.

Genes of a Desert People. One Israeli researcher is seeking clues to devastating genetic illnesses that affect Bedouins: Dr. Ohad Birk, head of the Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology at Ben-Gurion University of the Negev. He is also the director of a related institution, the Genetics Institute at Soroka University Medical Center.  As part of his genetic research, Birk has been working with Dr. Khalil Elbedour, a Bedouin physician from Israel, to identify the diseases that have struck hundreds of children in the Negev Bedouin population in the last decade. The project had strong support from Rivka Carmi, acting president of the university when the program was launched. (She has since become its president.)  Carmi, a physician and genetics professor herself who has been living and practicing in the Negev region since she graduated from medical school, told visiting journalists that part of her vision for "transforming the Negev" included improving life for the region's large Bedouin population. Some 500 Bedouin students, half of them women (a fact worth noting in a highly male-dominated culture), attend the university.

But many Bedouin children are born with rare, severe illnesses and deformities. The reason, Birk said, is that under Bedouin tradition, first cousins often marry. When the population lived a nomadic desert life, the tradition helped to keep extended families together and strengthen the family unit. But today - when some 65 percent of the Negev Bedouins still marry first or second cousins - the result has been to increase the odds that both parents will carry the same mutation, upping the chances for having a child with a genetic disease or deformity.

In addition, Birk said, many husbands have two or three wives, often from the same extended family, and the Negev Bedouins have an average of eight to 10 children, all factors that work toward increasing the prevalence of genetic diseases.

Birk and Elbedour, along with Dr. Izzeldin Abuelaish, a Palestinian physician from the Gaza Strip, are trying to do something to change that. Their approach is two-pronged: First, they try to identify the genes that cause the diseases, many of which kill children in the first few years of life or leave them permanently disabled. Blindness and severe mental retardation are particularly common. So far, eight new mutant genes, plus new mutations in previously identified genes that were associated with diseases, have been found.

The second approach is to offer premarital genetic counseling and prenatal testing to Bedouin couples - not an easy task in a closed society of proud individuals who don't take well to meddling by outsiders. Still, Birk and the other doctors are working with Muslim leaders to get across the message about genetic counseling and about the dangers of marrying close relatives. Some of it, at least, seems to be working. Birk said that in the last year more than 20 couples decided to end pregnancies after prenatal testing showed that their fetuses carried severe terminal diseases.

New York Times March 21, 2006 A Hunt for Genes That Betrayed a Desert People By DINA KRAFT


By JIM ABRAMS, Associated Press Writer Thu Apr 24, 2008 Senate passes genetic discrimination bill WASHINGTON - People learning through genetic testing that they might be susceptible to devastating diseases wouldn't also have to worry about losing their jobs or their health insurance under anti-discrimination legislation the Senate passed Thursday.
Niemann Pick's_disease
Gaucher's disease
Common Genetic Disorders LAbcorp 

Approximately 85-90% of patients with typical clinical features of HFHC are homozygous for the C282Y mutation. However, only 40-50% of homozygous patients demonstrate clinical disease.

Quest LAB DNA test for hemochromatosis Chantilly Lab
Code: 10249 Hereditary Hemochromatosis DNA Mutation Analysis [35079X]
This assay detects the two mutations in the HFE gene, C282Y (NM_000410.2: c.845G>A) and H63D (NM_000410.2: c.187C>G), that are commonly associated with HH. The mutations are detected by multiplex-polymerase chain reaction (PCR) amplification, followed by digestion of the amplification products with the restriction enzymes RsaI and NlaIII, for the detection of the C282Y and H63D mutations respectively. Fluorescent-labeled restriction fragments are detected by capillary electrophoresis. Code: 141661 Hereditary Hemochromatosis DNA MutationAnalysis,NY [36193X]

Clinical Chemistry. 2001;47:1147-1156.
Hereditary Hemochromatosis Since Discovery of the HFE Gene
Elaine Lyona1 and Elizabeth L. Frank Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84132.
PowerPoint review of genetic testing techniques…
Nuclear Sequencing is latest…Pagon
Genetic Conditions
Genetic Testing for Ashekenazi Screening
Volume 347:1867-1875  December 5, 2002  Number 23, Genetic Testing Burke, M.D., Ph.D.

Genetic testing can provide dramatic clinical benefits. A child known to have multiple endocrine neoplasia type 2 (MEN-2) can be spared medullary carcinoma by undergoing prophylactic thyroidectomy (Figure 1),

1 and an adult with hereditary hemochromatosis can be spared cirrhosis by the early initiation of phlebotomy treatment.

2 Genetic testing can also provide diagnostic and prognostic information that aids in difficult clinical decision making. For example, a test for a deletion in the dystrophin gene, the cause of Duchenne's muscular dystrophy, can be used to identify women who are carriers of this condition (Figure 2).

3 A carrier may avoid having an affected child by avoiding pregnancy or by undergoing prenatal testing for Duchenne's muscular dystrophy, with possible pregnancy termination if the fetus is found to be affected.

Cardiovascular Disease

From Nature Clinical Practice Cardiovascular Medicine
Genetic Testing in Cardiac Disease: From Bench to Bedside
Posted 10/09/2006 Allison L Cirino; Carolyn Y Ho Author Information 
What types of heart disease may be caused by inherited traits?
The most common inherited cardiovascular diseases are:
Hypertrophic cardiomyopathy (HCM)
Dilated Cardiomyopathy (DCM)
Inherited Arrhythmias
Marfan Syndrome
Familial Aortic Aneurysm (FAA)
Biotech Firm Identifies Five Genes Associated with Heart Disease
Oct 15 2007, Celera and Collaborators Identify a Five-Gene Genetic Risk Score(TM) That Predicts Risk of Coronary Heart Disease

Genetic Risk Score(TM) (GRS) based on five gene variants that predicts risk for coronary heart disease (CHD). These variant genes were KIF6, MYH15, PALLD, SNX19, and VAMP8. The GRS of each ARIC participant depended on how many of these risk variants an individual had. After adjusting for traditional risk factors, those individuals with a high risk GRS had a 57% increased risk of incident CHD, which is similar to the magnitude of risk for CHD associated with smoking, hypertension, hypercholesterolemia, or obesity.
Heart Disease

Apo-E And Heart Disease
Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD
Apo E genotype DNA test to identify the apo E2/E2 genotype. This genotype is diagnostic for broad beta disease when associated with combined elevation of cholesterol and TG. The test is typically performed by polymerase chain reaction followed by restriction enzyme cleavage and gel electrophoresis. Accuracy of E2/E2 detection is >99%.
Genetics of Heart Disease - Inheritance Patterns - Review Article
Researchers have identified more than 250 genes that may play a role in CAD. 

Information on Prolastin treatment for alpha -1-antitryin deficiency
alpha1-Proteinase Inhibitor (Human), Prolastin is a sterile, stable, lyophilized preparation of purified human Alpha1-Proteinase Inhibitor (alpha1-PI) also known as alpha1-antitrypsin. Prolastin is intended for use in therapy of congenital alpha1-antitrypsin deficiency.
How to Diagnose Iron Overload,  Mercola By J. Mercola, D.O.
Personalized Medicine: Real Clinical Examples!
Whole Genome Sequencing Costs Continue to Drop by Dr. Hsien-Hsien Lei Posted February 11, 2008 in DNA Inventions and Gadgets, DNA Testing, DNA in General
Genome Technology Magazine May 2008

Other Online Genetic Testing Services

Alzheimer's disease, Breast cancer, Celiac disease, Colon cancer, Crohn's disease, Diabetes, type 2, Glaucoma, Graves' disease, Heart attack, Lupus, Macular degeneration, Multiple sclerosis, Obesity, Osteoarthritis, Prostate cancer, Psoriasis, Restless legs syndrome, Rheumatoid arthritis

Navigenics scans your DNA for markers associated with many common diseases.
We have rigorous standards for deciding which health conditions to include in Navigenics Health Compass.
Navigenics Debuts Gene Dx Service, Allies With Mayo to Study How Patients Use Data [April 9, 2008]
23andMe How 23andMe's services work:

23andMe sends individuals a saliva kit containing a bar-coded tube for saliva collection. Customers then use the enclosed mailing materials to send their samples to 23andMe's contracted laboratory. The DNA is then extracted and exposed to a microchip-like device made by Illumina, Inc., a leading developer of genetic analysis tools (Nasdaq: ILMN), that reads more than half a million points in the individual's genome, including a proprietary set of over 30,000 information-rich markers, chosen by 23andMe scientists, to produce a detailed genetic profile.

Once the analysis has been completed, individuals are able to use their own private login to access their data via 23andMe's secure website. Using 23andMe's web-based tools, individuals can explore their ancestry, see what genetic research means for them and compare themselves to friends and family members.
Participants become part of a community that works together to advance the overall understanding of the human genome.

23andMe: Will the personal-genomics company need Big Pharma to make money?
Knome is the first personal genomics company to offer whole-genome sequencing and comprehensive analysis services for individuals. Based in Cambridge, Massachusetts, we work alongside leading geneticists, clinicians and bioinformaticians from Harvard and MIT to enable our clients to obtain, understand, and share their genomic information in a manner that is both anonymous and secure.
We are currently offering 20 individuals the opportunity to participate in our initial launch phase.  By being amongst the first individuals in history to have their whole genome sequenced, these participants will help pioneer the emerging field of personal genomics.
DeCodeME. Online Genetic Testing Service, Our current list of diseases includes: Abdominal Aortic Aneurysm, Age-related macular degeneration, Alcohol Flush Reaction, Alzheimer's disease, Asthma, Atrial fibrillation, Bitter Taste Perception, Breast Cancer, Celiac Disease, Colorectal Cancer, Crohn's disease, Exfoliation Glaucoma, Heart Attack, Hemochromatosis, Intracranial Aneurysm, Lactose Intolerance, Lung cancer, Male Pattern Baldness, Multiple sclerosis, Nicotine Dependence, Obesity, Peripheral Arterial Disease, Prostate cancer, Psoriasis, Restless legs syndrome, Rheumatoid arthritis, Type 1 Diabetes, Type 2 Diabetes, Venous Thromboembolism .
Media Round-Up: Personal Genome Services 23andMe, deCODEme, Navigenics
As promised, here’s a round-up of media on the new personal genome services.

Genetic Testing Under the Microscope
MDL LAb Genetic Testing Service
Tests Offered

Thrombosis Testing:
Prothrombin Gene Mutation
PAI-1 Gene Mutation
Factor V Leiden Mutation
MTHFR C677T and A1298C Mutations
Glycoprotein IIIA (A1 vs A2)
Stromelysin-1 5A/6A Polymorphism
Endothelial Nitric Oxide Synthase (eNOS) T-786C Mutation
Apolipoprotein E Genotyping (Apo E)
Pharmacogenetic Testing

Warfarin (coumadin) Metabolism Panel
DPD Enzyme Deficiency (Dihydropyrimidine Dehydrogenase)
UGT1A1 Camptosar (irinotecan) Metabolism

CYP2D6, CYP2C9, CYP2C19 Drug Metabolism Panel
CYP2D6 only
CYP2C9 only
CYP2C19 only
Vitamin B12 Deficiency by uMMA

The Future of Medicine
Megatrends in Medicine that Will Improve Your Health Care and Your Quality of Life, Excerpts from The Future of Medicine
Genomic Medicine in the Future. In the future, an individual will be able to go to the doctor for a regular checkup and give a small sample of blood, or maybe even just let the doctor take a mouth swab. This will provide a DNA sample that would then be placed on a genetic "microchip" or other device and quickly be genotyped to give a genetic profile of the patient. The doctor will use the information to tailor the medical treatment for that patient. Lifestyle changes or medicine will be suggested to prevent the occurrence of diseases to which the patient is genetically susceptible, or at least to reduce the risk or severity of such diseases. If medication must be prescribed, the doctor will also use this genetic profile before choosing the medicine, to make sure that "the right medicine for the right patient" is chosen: one that works and will not harm the patient or cause side effects.
Fast Forward to 2020: What to Expect in Molecular Medicine
The Future of Medicine A review of Rick J. Carlson and Gary Stimeling's The Terrible Gift: The Brave New World of Genetic Medicine
DNA and You, Thoughts on the rise of personalized genomics. by Matt Mealiffe, M.D.
Personalized Medicine for the 21st Century

The coming Revolution in Physics, Biochemisty  and Medicine, Peter Fraser, Milo WOlf ideas.

Excellent Video Presention on The New Human Genome Era

Video presentation Personalized Medicine: How the Human Genome Era Will Usher in a Health Care Revolution
Francis S. Collins, M.D., Ph.D. Personalized Medicine Coalition February 10, 2005

risk prediction
colon cancer- offer colonoscopy
drug metabolism
develope new therapies..drugs or gene therapy

JAMA January Sodium channell gen atrial fibrillation, cardiomyopathy SCN5A Olsen etal JAMA JAn 2005

Lancet Cly2019Ser LRRK2 common in familial Parkinson's disease
this is 7th gene associated with Parkinson's Disease
Identify who is at risk for Parkinsons in family where gene is identified.

Individualized preventive medicine, prevention.
BEst possible window for developing drug thereapy.
Experiment of nature which tells you the a gene and protein product is involved in pathogenesis.
Away from small molecule reseah into thsi direction.
That kind of discovery os gpoing to accelerate dramatically over the next few years.  In past, most variants were discovered in wknown diseases.

We now have ability to look at all the genes there is only about 25,000 of them. progect
understand genetic variation, all data goes into public domain.
Generate MAp of incredible richness. View genetic variation of greater depth than we had imagined.  High density genotyping.

Crohn's disease tends to run infamilies. tested 248,000 snps. Postitve controls, another 10 or so. Drug target approach. thats an example.

NEJM 2004 351 2817-26
Tamoxifen node neg breast cancer multigene assay. gene expression risk for distant recurrance.compelling correlation. Multi-gene Assay predicts recurrance of Tamoxiphen treated node neg breast cancer. 80% cured and dont need chemo.  This identifies high risk group that need chemo.

Roche product Amplichip CYP450 NEJM Caraco 2004 Predict drug metabolism. Iressa (gefinitib) genome based drug that blocks EGF receptor kinase. NEJM 2004 350 2129-39 Some patients had dramatic response.  Restricted ito individuals who have mutastions in kinase domain of EGF receptor. 
Kinase inhibitor sensistve.

NEJM 2005 352, 441 -9 I131 Tositumomab Therapy sustained remission.
PCR analysis of BCL2 gene follicular lymphoma predicts clinical response genome based drug. EnteroLab Celiac Disease Testing.

Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314

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