What is DNA Diagnostic Tests?
In the past 10 years considerable progress has been made in the diagnosis of hereditary disorders at the DNA level. Many monogenic disorders can now be examined at the gene level; such examination has led to a better understanding of the molecular basis of these disorders and made carrier detection and prenatal diagnosis possible. Each year, more and more monogenic disorders can be added to the list of diseases that can be diagnosed by DNA analysis. Future research will be devoted to the identification of genes responsible for other known monogenic hereditary disorders, the elucidation of the molecular lesion associated with chromosomal abnormalities, and the characterization of the genes and gene defects involved in the common multifactorial diseases. The goal of diagnosis is the identification of the genetic defect in affected patients, persons destined to be affected, and carriers.

The gene based diagnosis measures various DNA markers which are widely replicated genetic risk factors for common diseases like Diabetes, cancer, heart diease etc. It identifies genetic risk for the diease, dependent/ independent of family history.

By knowing and understanding genetic risk, it may be possible to take actions that reduce or minimize the likelihood of an individual developing the disease condition.

What is the basic principle of the test?
Detection of SNPs (single nucleotide polymorphism) – single letter variations in the sequence of the genome on particular chromosomes which have been linked to increased risk of various diseases. This provide an important new means of identifying those who are at elevated inherited risk of developing such conditions independent of other risk factors. These risk variants are the first widely-replicated, common genetic variants ever found to associate with substantially increased risk of public health problems.

How the SNPs are related to diseases?
Each person's genetic material contains a unique SNP pattern that is made up of many different genetic variations. Researchers have found that most SNPs are not responsible for a disease state. Instead, they serve as biological markers for pinpointing a disease on the human genome map, because they are usually located near a gene found to be associated with a certain disease. Occasionally, a SNP may actually cause a disease and, therefore, can be used to search for and isolate the disease-causing gene.

To create a genetic test that will screen for a disease in which the disease-causing gene has already been identified, scientists collect blood samples from a group of individuals affected by the disease and analyze their DNA for SNP patterns. Next, researchers compare these patterns to patterns obtained by analyzing the DNA from a group of individuals unaffected by the disease. This type of comparison, called an "association study", can detect differences between the SNP patterns of the two groups, thereby indicating which pattern is most likely associated with the disease-causing gene. Eventually, SNP profiles that are characteristic of a variety of diseases will be established. Then, it will only be a matter of time before physicians can screen individuals for susceptibility to a disease just by analyzing their DNA samples for specific SNP patterns.

SNPs related tests are available for various diseases like:

1. Type 2 diabetes

Type 2 diabetes is a chronic (lifelong) disease marked by high levels of sugar in the blood. It begins when the body does not respond correctly to insulin, a hormone released by the pancreas. Type 2 diabetes is the most common form of diabetes.

Cause:

• Diabetes is caused by a problem in the way your body makes or uses insulin. Insulin is needed to move glucose (blood sugar) into cells, where it is used for energy.
• If glucose does not get into the cells, the body cannot use it for energy. Too much glucose will stay in the blood, causing the symptoms of diabetes.
• There are several types of diabetes. This article focuses on type 2, which usually occurs with obesity and insulin resistance.
• Insulin resistance means that fat, liver and muscle cells do not respond normally to insulin. As a result they do not store sugar for energy. Since the tissues do not respond well to insulin, the pancreas produces more and more insulin.
• Because sugar is not getting into the tissues, abnormally high levels of sugar build up in the blood. This is called hyperglycemia. Many people with insulin resistance have hyperglycemia and high blood insulin levels at the same time. People who are overweight have a higher risk of insulin resistance, because fat interferes with the body's ability to use insulin.
• Type 2 diabetes usually occurs gradually. Most people with the disease are overweight at the time of diagnosis. However, type 2 diabetes can also develop in those who are thin, especially the elderly.
• Family history and genetics play a large role in type 2 diabetes. Low activity level, poor diet, and excess body weight (especially around the waist) significantly increase your risk for type 2 diabetes.

Other risk factors include:

• Age greater than 45 years
• HDL cholesterol of less than 35 mg/dL or triglyceride level of greater than 250 mg/dL
• High blood pressure
• History of gestational diabetes
• Previously identified impaired glucose tolerance by your doctor
• Race/ethnicity (African Americans, Hispanic Americans, and Native Americans all have high rates of diabetes)
  

Symptoms:

Often, people with type 2 diabetes have no symptoms at all. If you do have symptoms, they may include:

• Blurred vision
• Erectile dysfunction
• Fatigue
• Frequent or slow-healing infections
• Increased appetite
• Increased thirst
• Increased urination
  

Treatmet:

The immediate goal of treatment is to lower high blood glucose levels. The primary treatment for type 2 diabetes is exercise and diet.

Medication:

When diet and exercise do not help maintain normal or near-normal blood glucose levels, your doctor may prescribe medication. Most people with type 2 diabetes will eventually need more than one medication to maintain good blood sugar control. Different groups of medications may be combined or used with insulin.

Some of the most common types of medication are listed below. They are taken by mouth or injection.

• Alpha-glucosidase inhibitors (such as acarbose) decrease the absorption of carbohydrates from the digestive tract to lower after-meal glucose levels.
• Biguanides (Metformin) tell the liver to decrease its production of glucose. This decreases glucose levels in the bloodstream.
• Injectible medications (including exenatide and pramlintide) can lower blood sugar.
• Meglitinides (including repaglinide and nateglinide) trigger the pancreas to make more insulin in response to the level of glucose in the blood.
• Oral sulfonylureas (like glimepiride, glyburide, and tolazamide) trigger the pancreas to make more insulin.
• Thiazolidinediones (such as rosiglitazone) help insulin work better at the cell site. They increase the cell's sensitivity (responsiveness) to insulin. Rosiglitazone may increase the risk of heart problems. Talk to your doctor.

If you continue to have poor blood glucose control despite lifestyle changes and taking medicines by mouth, your doctor will prescribe insulin. Insulin may also be prescribed if you have had a bad reaction to other medicines. Insulin must be injected under the skin using a syringe. It cannot be taken by mouth.

Diagnostic test:

Regular self-testing of your blood sugar tells you how well your combination of diet, exercise, and medication are working. Tests are usually done before meals and at bedtime. More frequent testing may be needed when you are sick or under stress.

The risk assessment of type 2 diabetes can be done iwth deCODET2tm analysis.

2. Atrial Fibrillation

Atrial fibrillation/flutter is a heart rhythm disorder (arrhythmia). It usually involves a rapid heart rate, in which the upper heart chambers (atria) are stimulated to contract in a very disorganized and abnormal manner.

Cause:

Causes of atrial fibrillation include

• Alcohol use (especially binge drinking)
• Congestive heart failure
• Coronary artery disease (especially after a heart attack or coronary artery bypass surgery)
• Heart surgery
• High blood pressure (hypertension)
• Hypertrophic cardiomyopathy
• Medications
• Overactive thyroid gland (hyperthyroidism)
• Pericarditis
• Valvular heart disease (especially mitral stenosis and mitral regurgitation)
  

Symptoms:

You may not be aware that your heart is not beating in a normal pattern, especially if it has been occurring for some time.

Symptoms may include:

• Pulse that feels rapid, racing, pounding, fluttering, or too slow
• Pulse that feels regular or irregular
• Sensation of feeling the heart beat (palpitations)
• Shortness of breath while lying down
• Confusion
• Dizziness, light-headedness
• Fainting
• Fatigue
• Note: Symptoms may begin or stop suddenly.

Treatment:

In certain cases, atrial fibrillation may need emergency treatment to to get the heart back into normal rhythm. This treatment may involve electrical cardioversion or intravenous (IV) drugs such as dofetilide, amiodarone, or ibutilide. Drugs are typically needed to keep the pulse from being too fast.

Long-term treatment varies depending on the cause of the atrial fibrillation or flutter. Medications to slow the heartbeat may include:

• Beta-blockers
• Calcium channel blockers
• Digitalis

Anti-arrhythmic medications may be used to get the heart back into a normal rhythm. These medications may work well in many people, but they can have serious side effects. Many patients may go back to atrial fibrillation even while taking these medications.

Blood thinners, such as heparin and warfarin (Coumadin) reduce the risk of a blood clot traveling in the body (such as a stroke). Because these drugs increase the chance of bleeding, not everyone will use them. Antiplatelet drugs such as aspirin or clopidogrel may also be prescribed. Your doctor will consider your age and other medical problems to decide which drug is best.

Some patients with atrial fibrillation, rapid heart rates, and intolerance to medication may need a catheter procedure on the atria called radiofrequency ablation.

For some patients with atrial flutter, radiofrequency ablation can cure the arrhythmia and is the treatment of choice. Some patients with atrial fibrillation and a rapid heart rate may need the radiofrequency ablation done directly on the AV junction (the area that normally filters the impulses coming from the atria before they move on to the ventricles).

Ablation of the AV junction leads to complete heart block. This condition needs to be treated with a permanent pacemaker.

Diagnostic Test:

The health care provider may hear a fast heartbeat while listening to the heart with a stethoscope. The pulse may feel rapid, irregular, or both. The normal heart rate is 60 - 100, but in atrial fibrillation/flutter the heart rate may be 100 - 175. Blood pressure may be normal or low.

An ECG shows atrial fibrillation or atrial flutter. Continuous ambulatory cardiac monitoring -- Holter monitor (24 hour test) -- may be necessary because the condition often occurs at some times but not others (sporadic).

Tests to find underlying heart diseases may include:

• Coronary angiography
• Echocardiogram
• Electrophysiologic study (EPS)
• Exercise treadmill ECG
• Nuclear imaging tests
  

Risk assessment of AF can be done with deCODEAFtm analysis.

3. Glucoma

Glaucoma is a disease of the major nerve of vision, called the optic nerve. Glaucoma is characterized by a particular pattern of progressive damage to the optic nerve that generally begins with a subtle loss of side vision (peripheral vision).

Causes:

Elevated pressure in the eye is the main factor leading to glaucomatous damage to the eye (optic) nerve. The increased pressure destroys the nerve cells in the eye, which leads to vision loss. At first, you may have blind spots only in your peripheral, or side, vision. If your glaucoma isn't treated, your central vision will also be affected. Vision loss caused by glaucoma is permanent.

Symptoms:

Most people who have glaucoma don't have any symptoms. You might not realize that you're losing vision until it's too late. Half of all people with loss of vision caused by glaucoma are not aware they have the disease. By the time they notice loss of vision, the eye damage is severe.

Rarely, an individual will have an acute (sudden or short-term) attack of glaucoma. In these cases, the eye becomes red and extremely painful. Nausea, vomiting and blurred vision may also occur.

Treatment:

Glaucoma can be treated with eyedrops, pills, laser surgery, eye surgery or a combination of methods. The purpose of treatment is to lower the pressure in the eye so that further nerve damage and vision loss are prevented.

Diagnostic Tests:

You won't know you have glaucoma until you notice vision loss. Since glaucoma causes no symptoms other than vision loss, it is important that you have a complete eye exam by an ophthalmologist regularly. An ophthalmologist is a doctor who is trained to provide care for the eyes, including the diagnosis and treatment of glaucoma. Your ophthalmologist can measure your eye pressure, examine your optic nerve and evaluate your central and peripheral vision. Early diagnosis and treatment of glaucoma can prevent damage to the eye's nerve cells and prevent vision loss.

Risk factors for glaucoma include older age, black race, family history of glaucoma, high pressure in the eyes, diabetes, hypertension and near-sightedness. Risk assessment of glucoma is done through GlucomaTM analysis.

4. Prostate Cancer

Link t Prostate cancer resource page

5. Breast Cancer

LInk to Breast cancer resource page

Courtesy:Diagnosis of genetic disorders at the DNA level., Erratum in:
N Engl J Med 1989 Jul 6;321(1):56.

http://www.ncbi.nlm.nih.gov/About/primer/snps.html

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