1. Genetic Epidemiology Lecture 13 PS Timiras

3. A Few Definitions GENOME: THE COMPLETE SET OF GENES OF AN ORGANISM GENOTYPE: THE GENETIC CONSTITUTION OF A CELL OR AN ORGANISM PHENOTYPE: THE OBSERVABLE PROPERTIES OF AN ORGANISM THAT HAVE DEVELOPED UNDER THE COMBINED INFLUENCES OF  ｷ The genetic constitution of the organism, and  ｷ The effects of environment6al factors PHENOME: GENOME + ENVIRONMENT THE CONSTITUTION OF AN ORGANSIM COMBINING GENETIC AND ENVIRONMENTAL FACTORS

4. Many of the changes in normal function and common diseases are known to have a genetic component Several thousands (7,000?) rare diseases are inherited in a Mandelian fashion one gene  one disease Many genes for the phenotype have been mapped  better understanding of these changes Correlation between Aging and Genetic Epidemiology

5. Genetic variation interacts with the environment to modify the risk of disease e.g. cancer coronary heart disease neurologic, psychiatric diseases, etc. Monogentic (one gene only) or multigenetic (several genes) may  or  the risk of developing a certain trait

6. Genetic Factors in Alzheimer’s Disease Risk of late onset AD ­ or ¯depending on mutation type The risk is ­ (12 times) in the presence of AP0E4 (16 % of the general population carry this mutation) The risk is ¯ halved in the presence of APO E2 ( 7% of the general population carry this mutation) As in other complex genetic traits there is an “incomplete correlation” between the APOE4 genotype and the APOE4 phenotype APOE4 may contribute to AD risk, but may not, by its presence alone, cause the disease

7. In examining the role of genes in the etiology of complex disease we must distinguish: 1. causal genes: single gene mutation leads to disease e.g.Huntington disease 2.susceptibility genes: associated with the disease but themselves not sufficient to cause the disease

8. 1.Determination of familial aggregation 2.Determination of evidence of familial aggregation discrimination between environmental/cultural and genetic factors that may contribute to the mutation clustering 3.Determination of genetic factors and their identification Determination of genetic participation to disease

9. Complex disease genes express traits: (a) that show no clear Mendelian inheritance (one gene/ one phenotype); (b) but have moderate to high evidence of genetic inheritance; (c) exhibit familial aggregation cases (d) are either polygenic, that is, involve multiple genes or (e) are multifactorial, that is, involve multiple genes interacting with the environment.

10. Ways in which genetic susceptibility may influence a disease: (a)by itself, (b)by making the carrier more susceptible to the disease, or (c)by exacerbating the expression of a risk factor or the risk factor may exacerbate the genetic effects

11. Social /economic /ethical considerations “pro” For the elderly: “medical assistance denied or rationed“ arguments “pro”  cost of medical care  cost of Medicare programs not all elderly are poor and those who are not want to profit from Federal programs

12. Social /economic /ethical considerations “Contra” 1.heterogeneity of elderly population 2.denying access to high technology care 1.to the elderly will not substantially decrease overall health costs because most expenses are incurred in young ages 3.difficulty in managing ethical choices and legal consequences

13. Cataract: example of complex genetic/environmental disease Cause: hardening yellowing of the crystalline lens of the eye necessary for accommodation Genetic factors: more frequent in females than males progresses with advancing age is found in twins more frequent in light colored eyes Environmental factors: diabetes exposure to ultraviolet light exposure to pollutants (e.g. tabacco smoke)

14. At Death Bed Heroic Measures Humanistic Medical Care

15. Pharmacogenetics or Pharmacogenomics Individualization of drug treatment according to each patient’s genetic constitution (i.e.based on an understanding of the genetic basis in patient responses to drugs)

16. A New Image of Aging Focuses not only on treating diseases but also on preventing them by: –improving physiologic competence –better and continuing life-long education –adopting healthier /hygienic lifestyles –promoting the discovery of new medical technologies