Genetic Basis of Common Diseases PDF

Ass prof Nikolina Elez-Burnjaković Genetic basis of common diseases  Medical genetics usually focuses on the study of rare and monogenic disorders Conditions that have the largest share in general morbidity and mortality: COMMON DISEASES??? Diabetes...

Ass prof Nikolina Elez-Burnjaković Genetic basis of common diseases  Medical genetics usually focuses on the study of rare and monogenic disorders Conditions that have the largest share in general morbidity and mortality: COMMON DISEASES??? Diabetes, malignancies, hypertension, cardiovascular disease, autism, schizophrenia, Crohn's disease, autism, Alzheimer's disease, atopic disease, venous thrombosis, senile macular degeneration…………… They do not have a simple inheritance mechanism…. They have considerable impact on public health.  Hemophilia Osteogenesis imperfecta Duchenne muscular Congenital hip dislocation Tuberculosis dystrophy GENOTYPE ENVIRONMENT Phenylketonuria Diabetes Scurvy Galactosemia Rare Common Genetically simple Genetically complex (monofactorial) (multifactorial) Common diseases occur as a result of the complex interaction of a number of genes (known as polygenic inheritance) with the influence of the environment, which is called multifactorial inheritance.  In a very small number of common diseases, genetic causes are found in a small number of genes In most cases, the genetic basis is a hereditary / genetic predisposition or susceptibility genetic susceptibility Increased likelihood or chance of developing a particular disease due to the presence of one or more gene mutations and/or a family history that indicates an increased risk of the disease. Also called genetic predisposition.  If in the basis of disorder is a genetic marker, then tests can identify people who are genetically susceptible to a particular disorder. The benefits of these tests depend on the procedure that follows. …………  Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. Huge numbers of direct-to-consumer genetic tests. Direct-to-consumer genetic testing provides people access to their genetic information without necessarily involving a healthcare provider or health insurance company in the process. Companies that build, market, sell, and ship their products themselves, without middlemen.  SOME ADVANTAGES OF GENETIC TESTING INCLUDE: A sense of relief from uncertainty Reduce the risk of cancer by making certain lifestyle changes if you have a positive result In-depth knowledge about your cancer risk Information to help make informed medical and lifestyle decisions Opportunity to help educate other family members about potential risk Earlier detection, which increases the chance of a successful outcome You can discover what traits your parents passed down to you You may discover living relatives You can find out cool facts about your body  SOME DISADVANTAGES, OR RISKS, THAT COME FROM GENETIC TESTING CAN INCLUDE: Testing may increase anxiety and stress for some individuals. There are psychological implications Testing does not eliminate a person's risk for cancer. Results in some cases may return inconclusive or uncertain. There isn’t much counseling for dealing with results DNA tests are not 100 percent reliable Positive results could be taken too far They can be expensive You cannot use results for medical purposes The results may be difficult to interpret yourself  Forms and mechanisms of genetic predisposition Inheritance of a mutated gene whose altered product participates in a particular metabolic pathway Mutation of the FH gene causes Changing environmental factors, familial hypercholesterolemia reducing dietary cholesterol, avoiding leading to coronary heart disease risk factors: obesity, smoking, physical (CHD) inactivity Inheritance of an allelic variant (polymorphism) that leads to an increase in sensitivity to as yet undefined responses from the external environment De novo mutation during life and exposure to mutagens…. exposure to specific environmental factors Mutation of the SERPINA1 gene causes α1 antitrypsin deficiency, which causes pulmonary emphysema, but only in the case of exposure to industrial dust  Ways of proving genetic susceptibility to common diseases If the incidence of the disease in the 1. Population-migration research immigration group is kept low, then 2. Family research the genetic factor 3. Exploring the twins is more important 4. Adoption research If the incidence of 5. Investigation of the association of polymorphisms the disease in the immigration group 6. Biochemical research grows to the level 7. Animal models of the new population, then Analysis of metabolite, enzyme the environmental or hormone levels factor is more Some disorders do not benefit important from this approach - schizophrenia  Early familial form Genes: APP, PSEN1, PSEN2, MPO Late familial form Genes : APOE e4, ACE, PICALM  Genes: AAAS, CSF1R, DCTN1, DNMT1, GRN, LOC105375056, MAPT, NOTCH3, POLG, PRNP, SNCA, SNCA-AS1, SNCB, TREM2, TREML1, TYROBP  Genes: ATP13A2, AUP1, BAIAP2L2, CSF1R, DCTN1, EIF4G1, FBXO7, GBA, GBF1, GCH1, HTRA2, LOC105377329, LOXL3, LRRK2, NOTCH3 , PACRG, PARK7, PINK1, PINK1-AS, PLA2G6, POLG, PRKN, PRKRA, SLC6A3, SNCA, SNCA-AS1, SNCB, TAF1, TH, UCHL1, VPS35  AUTISM It begins in the first three years of life More common in boys Impaired development of socialization, poor verbal and nonverbal communication The cause is not clear….  DIABETES MELLITUS Monogenic forms of diabetes cused by one mutation 1. MODY (Maturity Onset Diabetes of the Young) 2. Neonatal diabetes - can be permanent or transient Diabetes mellitus type 1 – about 20 loci Diabetes mellitus type 2 – variants of many genes https://www.youtube.com/watch?v=46WG012RkHY https://www.youtube.com/watch?v=rvk5GR_jQSw  ak ! Bre