Bibliographic and web study

Main themes : means ethical considerations

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• Behavioral genetics

  • (Alon 2002)
    Multi-factorial inheritance combines genetic and environmental effects. Each factor contributes a relatively small part to the overall phenotype.
    Multi-factorial multi-genetic illnesses are usually divided into two categories:

    1. Continuous variation of the normal distribution--phenotypes that can be measured within the normal scale (i.e. blood pressure). A normal distribution is obtained and the mean is in the middle.

    2. Multi-factorial threshold trait--a threshold separates between the existence or absence of the phenotype.

    The curve of distribution obtained only predicts sensitivity for the illness rather than it's existence, since the illness appears only beyond a specific threshold, which represents a specific combination of defected genes. Mental illnesses (psychoses, affective disorders and neuroses) are multi-factorial illnesses, affected at a level of approximately 50% by inheritance. These diseases are not inherited in a simple Mendelian way, and, most probably, many genes are involved. Today, there is still no biochemical or molecular marker for any of the mental illnesses, and diagnosis of patients is obtained according to behavioral accepted scales. The aim of behavioral genetics is to understand the interaction between genes and behavioral variability among individuals
    

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  • (McGuffin P, 1999)
    Here, we outline some of the basic concepts and lines of evidence from quantitative genetics indicating that genes do have important influences in determining human behaviour but that this nearly always involves an interplay with the environment..[]..In our view, this means that DNA based population screening for complex psychiatric disorders (including Alzheimer's disease of late onset) will never become a reality but that screening for high risk relatives probably will.
  
  

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• General practice and genetics

  (Kumar S, 1999)
  General practitioners emphasised the need to build on current practice, whereas policy makers focused on transforming practice to include the new specialised roles and skills. New technologies such as genetics that require implementation in general practice should be integrated within existing generalist frameworks

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• Genetic diseases

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  • alpha 1 antitrypsin deficiency

    (Wilcke JT, 1998)
    Information about the risks of 1 antitrypsin deficiency may be of limited use, except to reassure him that he has little to fear since those who have never smoked rarely develop severe disease. Nevertheless, the consequences of an active approach and information policy for someone in the position of Nina's brother are preferable to the consequences of remaining in ignorance.
    

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  • Breast Cancer

    • Breast cancer family history

      (Lucassen 2001) The studies which have been published provide evidence that the detection rate of cancer in women under 50 with a family history of breast cancer is equivalent to that in women over 50 in the general population who are screened.

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    • Breast cancer counselling

      Meiser B, Halliday JL.2002
      Meta-analytic methods. A total of 12 studies, most of which measured several outcomes, met at least one of the inclusion criteria. A sufficiently large number of studies were available to assess the magnitude of effects on three outcomes: generalized psychological distress, generalized anxiety and accuracy of perceived risk of developing breast cancer. The quantitative synthesis showed that genetic counselling leads to statistically significant decreases in generalized anxiety, with an average weighted effect sizes of r = - 0.17 (p<0.01). In contrast, the reduction in psychological distress exhibited a trend towards statistical significance only, with r = -0.074 (p = 0.052). The impact of genetic counselling on the accuracy of perceived risk was associated with an effect size of r = 0.56 (p<0.01). Thus in this meta-analysis, we demonstrated the efficacy of genetic counselling in meeting two of its objectives: reducing women's anxiety levels and improving the accuracy of their perceived risk.
      

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  • Polycystic kidney disease (PKD)

    (Grantham JJ.2002)
    and we quickly learned that uncommon genetic disorders could lead to the discovery of novel molecules in metabolic and structural pathways. And that is just what happened in the PKD field. The autosomal dominant form of PKD led to the discovery of a unique family of highly complex proteins long before they would have been selected from a gene or proteomic micro-array by some desperate graduate student or fellow. The chromosomal location of the major ADPKD genotype, PKD1, was defined in 1985 (3), a date that marks the beginning of a remarkable period of discovery.
    

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  • Thalassemia

    • (Dickerhoff R et all,1993)to identify carriers through haemoglobin electrophoresis screening, inform the carrier about the meaning of being a carrier, screen the woman's partner, refer for genetic counselling and suggest and explain prenatal diagnosis in case the partner is also a carrier. There is as yet no cure for thalassaemia and sickle cell disease, except for bone marrow transplantation in a few selected cases. Therefore, prenatal diagnosis presents a valuable method of preventing severe chronic diseases

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    • (Giordano PC et all., 2000) Without preventive measures a cumulative number of 1,000 severely affected patients can be expected in the Netherlands if information and carrier diagnostics are not efficiently offered at the GP level.

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    • GeneReview ; Each pregnancy of a couple in which both partners are heterozygous for a disease-causing HBB mutation has a 25% chance of producing an affected child, a 50% chance of producing an unaffected child who is a carrier, and a 25% chance of producing an unaffected child who is not a carrier.

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    • www.thalassaemia.org.cy
      • What is Thalassemia, chap. 1, see fig 5 to 7 by Dr. RINO VULLO et all.

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    • www.thalassemia.org

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  • Wilson's disease

    (Leung 2000)
    When a patient is found to have an inherited disease it has implications for the whole family. If screening is available the test is usually offered to all relatives who could be affected, but what if the patient does not want to tell his family about his diagnosis?

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  • Mental health diseases

    • manic-depressive disorders

      (Bertelsen A, 1977)
      This finding is in accordance with previous twin studies of manic-depressive disorders and confirms the evidence of a strong genetic factor