powerpoint presentation GENETICS PPT1.pptx

powerpoint presentation on genetics

1. INTRODUCTION Genetic diseases make-up a large proportion of the total disease burden both in pediatric and adult populations. Modern medicine is placing increasing emphasis on the importance and prevention. Because genetics provides a basis for understanding the fundamental biological make up of the organism, it naturally leads to better understanding of the disease process. In many cases knowledge can lead to the actual prevention of the disorder and will lead to more effective treatment

2. GENITIC DISORDERS A genetic disorder is a disease that is caused by a change ,or mutation, in an individual’s DNA sequence. These mutations can occur randomly due to various causes. A mutated gene is passed down through a family and each generation of children can inherit the gene that causes the disease .

3. CAUSES Mutations Aneuploidy. Deletions Duplications Inversions Translocations

4. TYPES OF GENETIC DISORDERS Autosomal dominant genetic disorders: These disorders are caused when an individual has inherited the defective gene from single parent like PCKD Autosomal recessive genetic disorders: Such disorders manifest only when an individual has got two defective alleles of the same gene, one from each parent. These genetic disorders are inherited via the autosomal recessive pattern of inheritance.

5. CONTD… Sex- linked disorders X-linked dominant: . X-linked recessive: . Multi factorial genetic disorder: Such disorders are the result of genetic as well as environmental factors

6. COMMON GENETIC DISORDERS Down syndrome( Trisomy 21): One of the most commonest genetic disorders affecting 1 in 800 live births. It is chromosomal condition related to chromosome 21.Most cases of down syndrome result from Trisomy 21 which means each cell in the body has three copies of chromosome 21 instead of 2 copies, this extra genetic material disturbs the normal course of development causes characteristics features of down syndrome.

7. CLINICAL FEATURES Hypotonic: Low IQ, developmental delay. Neurologic: Hypotonic, Premature senility, Alzhemer’s onset in 40’s Facies : Flat occiput , microcephaly , small mandible, and maxillae, up slanting palpebral fissures, epicanthal folds, brush field’s spots in iris ENT: Furrowed prominent tongue, high arched palate, ear anomalies, frequent acute otitis media CVS: 40% have congenital heart defects, particularly endocardial cushion defects

8. Contd … GI: Duodenal, anal atresia and TE fistula MSK: Lax joints including dysplastic hips, vertebral anomalies Skin: Simian ( palmar ) crease, abnormal dermatoglyphics Hematologic: Leukemias (1% lifetime risk) Endocrine: Hypothyroidism Prognosis: Shorter life expectancy

9. Turner Syndrome It is genetic disorder in girls caused by missing or defective x chromosome. It occurs in 1 of 2000-2500 live births . Not all girls but some of them will show the following sign s Short stature Hearing disorders Failure of ovaries to develop Webbed neck or short neck Frequent ear infection in childhood Shortening of bones in hands Lower jaw smaller than normal Drooping eyelids, wandering eyes

10. Sickle cell anemia Sickle cell anemia is a disease passed down through families in which red blood cells form an abnormal sickle shape

11.   Symptoms Attacks of abdominal pain Bone pain Breathlessness Delayed growth and puberty Fatigue Fever Paleness Rapid heart rate Yellowing of eye and skin

12. Hemophilia It is a hereditary genetic disorder, where there is congenital deficiency of plasma coagulation factors that impair the body’s ability to control blood clotting or coagulation. It is an inherited in x linked recessive pattern. It is quite rare only 1/10000 births.

13. Thalassemia It is an inherited autosomal recessive blood disorder. In Thalassemia, the genetic defect , which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chain that makes up haemoglobin.This can cause the formation of abnormal hemoglobin molecules, thus causing anemia

14. Therapeutic Approaches Approach is closer in meaning to “treat” Metabolic Manipulation : Physicians have developed approaches to regulate the metabolic pathways associated with a number of disorders, including phenylketonuria ( PKU), sickle cell anemia, thalassemia and many others. Often , this form of metabolic manipulation can be accomplished by modifying a patient’s diet . In other cases , metabolic manipulation involves the use of small molecules or drugs to the target activity of protein linked disease.

15. Reducing the accumulation of toxins The intake of substances , which can not be metabolized by the body, should be reduced, especially if there is accumulation is potentially toxic, e.g. in galactosemia, galactose can not be metabolized adequately. As lactose in the milk is hydrolyzed in the body to glucose and galactose , milk in the diet of affected infant is substituted by nonlactose containing dietary formula to obviate damage due to excess of galactose in tissue.

16. Contd … The phenylketonuric infant is placed on a low protein diet to prevent irreversible neurological damage. Certain drugs like allopurinol inhibits xanthine oxidase and thus reduces the synthesis of uric acid and hence is useful in case of gout .

17. Promoting excretion of toxin The excretion of certain toxic metabolites can be promoted by chelating agents. For example , pencillamine promotes excretion of copper patients with Wilson disease which is a genetic disorder that prevents the body from getting rid of extra copper. In wilson disease, copper builds up in the liver , brain, eyes and other organs. Overtime , high copper levels can cause life threatening damage.

18. Induction or stabilization of enzymes Certain enzyme systems, which may be immature or reduced at certain phase of life may be induced or stabilized by the use of chemical agents. For example phenobarbitone is used for inducing the hepatic microsomal enzyme glucuronyl transferase in cases of neonatal hyperbillirubinemia which is yellow coloration of the skin and sclera in newborn with jaundice is the result of unconjugated billirubin.

19. Avoiding Drugs Certain drugs which precipitate adverse symptoms in metabolic disorders such as barbiturates in porphyria hepatica and oxidative agents in glucose -6 phophate dehydrogenase deficiency, should never be administered in these patients

20. Environmental protection Patient with hemophilia and osteogenesis imperfect should be protected from trauma and other environmental hazards to prevent excessive blessing and fractures. Replacement Therapy The deficiency of the metabolic end products may be made up by the replacement or administration of the product. Thus Thyroxine restores the thyroid function in familial goitergenous cretinism, adminstration of factor

21. Protein Augmentation In this approach physician treat patient by providing them with a purified form of missing or depleted protein. This protein add back approach has been used successfully to treat the patient suffering from a wide range of diseases including various membrane transport disorders like cystic fibrosis. In this approach protein be added to the out side of cells. This approach work best for replacing proteins that are normally present in the extracellular space.

22. Surgical Approaches Although more invasive, organ transplantation is also used to treat certain genetic disorder that affect particular organs. In some cases surgery can be used to repair an organ or tissue that has been targated by disease. For example Cleft lip

23. Therapeutic Applications of recombinant DNA Technology Biosynthesis of gene products Insulin used in the treatment of diabetes mellitus was previously obtained from pig pancreas. This has to be purified has to be used very carefully and even then it sometimes produced sensitivity reactions in patients. However with recombinant DNA technology microorganism can be used to synthesize insulin from human insulin gene.

24. Contd … This is inserted along with appropriate sequences to ensure efficient transcription and translation in to recombinant DNA vector such as plasmid and cloned in a microorganism such as E. coli. In this way large quantity of insulin can be produced. Recombinant DNA technology is being employed in the production of number of other biosynthetic products.

25. Contd … Protein Disease Insulin Diabetes mellitus Factor IX Hemophellia B Erythropoietin Anemia

26. Gene Therapy The deliberate introduction of genetic material into human somatic cells for therapeutic,prophylactic or diagnostic purposes. It includes techniques for delivering synthetic or recombinant nucleic acids,genetic vaccines ,DNA or RNA technologies such as RNA interference xenotransplantation of animal cells

27. Regulatory Requirements There has been publicity about the potential uses and abuses of genr therapy. Regulatory bodies have been established in several countries to oversee the therapeutic, technical and safety aspect of the gene could be distributed to both somatic and germ cells and thereby be transmitted to future generations,is morally and ethically unacceptable. Therefore all programs are focusing only on somatic cell gene therapy, in which the alternation in the genetic information is targated to specific cells tissues or organs in which the disorder is manifested.

28. Technical aspects 1. Gene Characterization: One of the basic prerequisites of gene therapy is that gene involved should have been cloned. This should include not only the structured gene but also the DNA sequences involved in the control and regulation of expression of that gene.

29. Contd … 2. Target cells, tissue and organ The specific cells, tissue or organ affected by the disease process must be identified and accessible before treatment options can be considered. Some of early attempts as treating the inherited disorder of hemoglobin, such as beta thalassemia, involved removing bone marrow from affected individuals, traiting it in vitro and then returning it to patient by transfusion

30. Contd … 3.Vector system This means by which a foreign gene is introduced need to be both safe and efficient.Vector is a DNA molecule used as a vechile to artificially carry the foreign genetic material into another cell. 4.Target organ: In many instances , gene therapy will need to be and should be directed and limited to a particular organ, tissue or body system

31. contd Gene transfer It can be carried out by either by ex vivo by treatment of cells or tissue from an affected individual in culture, with reintroduction into the affected individual or in vivo if cells can not be cultured or replaced in an affected individual. RNA modification It targets mRNA , either by suppressing mRNA levels or by correcting adding function to the mRNA.

32. Contd … Targated gene correction   A promosing approach is to repair genes in situ through cellular DNA machinery.   Somatic cell therapy Somatic cells can differentiate into cell types found in the tissue from which they are derive ed. They are usually described by reference to the organ of origin. For example BMT.

33. Research input Abstract  Recombinant activated factor VII ( rFVIIa , NovoSeven ® ) represents an effective treatment for hemophilia patients with inhibitors, but no consensus as to the best dosing regimen exists. We assessed the efficacy and safety of a rFVIIa ‘ megadose ’ (300 µg kg −1  bolus) as treatment for bleeds in three young inhibitor patients. Of 114 bleeds, 95 responded to a single dose. Pain relief was faster and therapy duration significantly shorter than with continuous infusion (CI) regimens or standard boluses (90 µg kg −1  every 3 h). Rebleeding occurred in 9.6% of cases and 19/114 episodes required a second bolus injection. Although rFVIIa consumption per bleed (median: 300 µg kg −1 ) was higher than with standard boluses (180–270 µg kg −1 ), patients found single bolus administration more convenient than recurrent injections or CI. With two exceptions, no complications occurred within 3 h of treatment, despite high FVII:C levels (median: 27.4 U mL −1 ; range: 19.8–54 U mL −1 ). Treatment of bleeds with a rFVIIa megadose in young inhibitor patients is effective and well tolerated

34.   Materials and methods This was an open-label, single center (National Israeli Hemophilia Center) study carried out between October 1999 and November 2001.Eligible patients were recruited by the National Hemophilia Center. Patients with hemophilia A or B, an inhibitor titer greater than 5 BU, and who presented with an acute hemarthroses , intramuscular or soft tissue bleeding episode were enrolled in the study. Exclusion criteria were: age above 40 years, presence of other hemostatic disease, personal or family history of thrombosis or thrombophilia , clinically significant abnormal blood biochemistry, previous treatment with rFVIIa or any other hemostatic agent during the 24 h prior to the first study dose, and previous evidence for hypersensitivity to rFVIIa . All patients (or their guardians) gave informed consent before entering the study. The concomitant use of hemostatic or antifibrinolytic agents other than rFVIIa was not permitted in patients treated with the megadose protocol.

35. RESULTS Three patients treated at the National Israeli Hemophilia Center received treatment under three treatment regimens ( CIa , CIb , and megadose ). Patients were HIV negative and aged 19, 16 and 22 years with inhibitor levels of 6 BU, 120 BU and 8 BU, respectively Bleeding episodes A total of 244 bleeding episodes in these three patients were treated with rFVIIa . Of these, 58, 72 and 114 episodes were treated using the CIa , CIb , and megadose protocols, respectively. Of the bleeds treated with the megadose protocol, 82/114 occurred in target joints. In all cases, hemostasis was achieved following rFVIIa administration.

36. CONCLUSION As we know that Genetic diseases make-up a large proportion of the total disease burden both in pediatric and adult populations. Modern medicine is placing increasing emphasis on the importance and prevention by implementing the different approaches by proper knowledge we can treat some of gnetic disorders which will be great achievement in reducing the large proportation of disease burden on population .