Interesting facts

The medical application of gene analysis

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The future of medicine, in which every human being is to sequence his entire genome in order to follow better, person-specific, preventive measures, is eagerly awaited by many medical professionals.

The fact that the approximately 30,000 human genes play a role for our health is indisputable. Currently, the largest German providers (www.novogenia.com) are already offering 800 different medical genetic testings. There are even more than 2,000 [1] worldwide. Among them there are many diagnostic tests for monogenic, some very rare diseases, as well as the genetic component of common endemic diseases which is becoming increasingly clear.

Genetic tests may have different applications in practice. On the one hand they serve to confirm a suspected diagnosis (such as in the case of cystic fibrosis - CFTR gene [6]) or for risk assessment of first-degree relatives (breast cancer - BRCA1 & BRCA2 gene [7]).

While some genetic findings represent an absolute fate for the patient's health, the other only show the increase risk of developing a disease. Since the development of many diseases depends on the interplay between genes and the environment/lifestyle, new prevention possibilities arise. „If we know our genetic predispositions even before the first symptoms manifest themselves, we can adjust our environment, so our lifestyles, so that we avoid certain risk factors and as such we may be able to prevent the development of disease,"

"** NEED TRANSLATION **" meint Dr. Daniel Wallerstorfer, wissenschaftlicher Leiter vom DNA Plus Zentrum für Humangenetik in Bayern.

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** NEED TRANSLATION **"** NEED TRANSLATION **.", so Dr. Wallerstorfer. "** NEED TRANSLATION **."

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Although a history in genetic disorders with high penetrance and dominant inheritance can achieve similar results as a genetic analysis, it has serious limitations.

For example, in the case of Chorea Huntington, the dominant gene defect that causes that each individual suffers from the disease (the so-called complete penetrance) is easy to track through a medical family history [15]. If a carrier of this defect has a child, chances are 50 % that the child will also be a carrier. A medical history can only speculate and estimate the probability of disease to 50 %. Only a genetic analysis may determine whether the genetic defect was inherited, and whether the child will suffer from the disease.

In diseases with incomplete penetrance (not all carriers of the mutation develop the disease), as the familial thrombophilia, it is even more difficult to draw relevant conclusions based on the medical history. These genetic defects are relatively frequent, in about 20-40 % of thrombosis cases. Approximately one in twenty Europeans is genetically predisposed to thrombophilia and subjected to an 8-fold risk of thrombosis [16-18]. If untreated, 10 % of the people having this predisposition develop a potentially fatal thrombosis [19]. Since these gene defects do not always lead to disease, and there are 50% chances that they are passed to the next generation, tracking them through the family history is a very difficult, if even possible, task.

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Practical examples

The predictive value of genetic testing often varies from disease to disease, from gene to gene and even from mutation to mutation. Moreover, such genetic analyzes provide different information and opportunities for prevention, depending on the patient. Here are some examples of well-studied genetic predisposition and prevention options.

Lactose Intolerance

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Familial Thrombophilia

By a single gene defect (Factor-V), the risk of thrombosis increased 8 times, and 10 % of the patients will suffer from thrombosis at some point in their life. If the patient has two genetic defects, the risk increases about 80 times and, if left untreated, it will lead to the development of the disease in most of the cases. According to studies, genetic defects are involved in approximately 40 % of thrombosis cases [6-19]. Lifestyle changes and drug therapies (particularly in high-risk situations, such as long flights or after surgery) may normalize these genetic predispositions.

These genetic predispositions are particularly dangerous for women. The use of contraceptives or hormone preparations doubles the individual risk of thrombosis, even without a genetic defect. When there is also a predisposition to thrombophilia, the risk of disease increases exponentially, up to 18 times [23, 24]. Therefore, it is recommended that women with a genetic disposition to thrombophilia switch to alternative non-hormonal contraceptives. The only problem is, there is hardly any woman concerned about this risk. The risk increases even more during pregnancy. The already 4-fold increased risk of thrombosis, increases now 60 times, due to the genetic predisposition; the condition should be strictly treated with low molecular weight heparin [25, 26].

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Familial Hypercholesterolemia

A genetic defect in the APOB gene increases the likelihood of hypercholesterolemia to 78-fold, while some defects in the LDLR gene even up to 1233 times [27-29]. These forms of hypercholesterolemia are often indistinguishable from acquired cholesterolemia, but may require a different treatment.

Osteoporosis

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The consequential health risks, such as lactose intolerance, cancer including a twofold to fourfold increased risk of non-Hodgkin’s lymphoma, a more than 30-fold increased risk of small intestinal adenocarcinoma, and a 1.4-fold increased risk of death, can be normalized by adequate treatment and a gluten-free diet.

Macular Degeneration

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Nutritional Genomics

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For example, dairy products are a recommended source of calcium. A diet rich in calcium plays an essential role for individuals who are genetically predisposed to bone loss (Osteoporosis). As such, dairy products are highly recommended, unless that person is among the 20 % of the population who are lactose intolerant, due to an inherited genetic defect [21]. In this case, the patient should completely switch from dairy products to other sources of calcium, such as broccoli or dietary supplements. Genetic predisposition to elevated cholesterol or triglycerides (Atherosclerosis), diabetes mellitus type 2 (Diabetes), the gluten / grain intolerance (Celiac Disease), the iron storage disease (Hemochromatosis) or Macular Degeneration, all require specific dietary changes, in order to optimally prevent these diseases. Through genetic analysis, we can find out which food categories are particularly important for an individual, and which should be avoided, based on the genetic predisposition.

Citations

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