Genetic Disorders

1. Genetic Disorders Chapter 11 Contd.AS SUPPLIMENT

2. Common diseases of Genetic order • Gaucher Disease • Huntington’s Disease • Hemophilia • Parkinson’s Disease • Phenylketonuria • Sickle Cell Anemia • Cystic Fibrosis • Down Syndrome • Alzheimer’s Disease • SCID: Severe Combine Immunodeficiency • Type I Diabetes • Achondroplasa • Autism • Others

3. There are four types of Genetic Diseases • 1. Single Gene: • Disorders caused by abnormality or mutation in the sequence of one gene • 2. Multifactorial: • caused by a combination of environmental as well as mutations in multiple genes • 3. Chromosomal: • Abnormalities in chromosome structure such as missing or extra copies • 4. Mitochondrial: • caused by a mutation in the non chromosomal DNA of the mitochondria.

4. GaucherDisease • Gaucher disease is a genetic disorder handed down from generation to generation. It is the most common of the lipid storage diseases. It is caused by deficiency of the enzyme, β-glucocerebrosidase. • When there is not enough of the enzyme, the fat can not be broken down and is stored primarily in the liver and spleen • Other body tissues, bones and organs may also be affected. In rare cases, it may also accumulate in the brain.

5. …General Signs and Symptoms • bone pain and fractures • easy bruising • fatigue • seizures • Liver and spleen enlargement

6. …GaucherDisease Treatment • In the past the only potential treatment was removal of the spleen (splenectomy). • This has given way to injections of a replacement synthetic enzyme (Cerezyme/Ceredase). • Gene therapy is an experimental approach. • A novel oral treatment has recently been evaluated. This drug is known as N-butyldeoxynojirimycin (OGT 918). • The mechanism of action is by inhibiting the formation of glucocerebroside.

7. Huntington’s Disease • Huntington’s Disease results from genetically programmed degeneration of nerve cells in certain areas of the brain. • This degeneration causes uncontrolled movements, loss of intellectual faculties, and emotional disturbance.

8. …Major Effects • Early signs of Huntington’s disease include mood swings and irritability, depression, loss of memory, and uncontrolled movements. • As the disease progresses, walking and speech become more difficult, and memory and intellectual functions continue to decline.

9. Hemophilia • Hemophilia is the oldest known bleeding disorder. • It is a sex-linked disorder, which is why it appears mostly in males. • Hemophilia is like any other sex-linked disorder, because the “hemophilia” gene is on the X chromosome. • 2 types of Hemophilia: • Hemophilia A: Lack the blood clotting protein factor VIII • Hemophilia B: Lack the blood clotting protein factor IX.

11. ..Hemophilia Treatment • Clotting factors: Given in differing doses according to the weight of the individual and the severity of the bleeding. • Recombinant DNA Techniques: Clotting factor genes are grown synthetically. • Clotting factor products from human blood plasma are not used due to chances of being contaminated with viruses such as HIV or Hepatitis.

12. ..Hemophilia Research Gene Therapy • A major focus of research in hemophilia centers. • Because only one defective gene is involved, replacing that gene effectively may cure hemophilia. • Although gene therapy may eventually replace treatment for individuals with hemophilia, it will not eliminate defective genes in carriers, who could still pass hemophilia to their children. • Currently studies are being conducted for type B hemophilia to determine the safety of the gene transfers.

13. Parkinson’s Disease • Parkinson’ s disease is a neurological condition that has a genetic component next to Alzheimer’s. • The chance of getting or developing Parkinson’s gets higher as age increases.

14. …Causes of Parkinson • DOPAMINE Chemical produced in the middle part of the brain that is responsible for organizing coordinated movements and to send this signal to the control centers of the brain. • In Parkinson’s disease, this chemical is not produced enough and functioning starts to shut down slowly & patient begins to lose control over many vital voluntary movements from swallowing to walking. • SYMPTOMS Some symptoms include hand tremor, muscle spasms, rigidity, lack of postural stability, memory loss, blurriness, drooling, and difficulty in voluntary movements.

15. ….ONGOING RESEARCH Parkinson • Nearly $70 million in research programs funded • Michael J. Fox Foundation. • National Parkinson Foundation.

16. Phenylketonuria (Pku) • Rare metabolic autosomal recessive disorder • Affects protein breakdown in the liver resulting in mental retardation & genetic Mutation occurs on Chromosome 12 • The mutated gene is supposed to code for a protein which produces phenylalanine hydroxylase • Without phenylalanine hydroxylase, phenylalanine (found in protein rich foods) cannot be converted to tyrosine • Excess phenylalanine in the body will result in mass production of phenylpyruvic acid • Phenylpyruvic acid cannot be absorbed by the kidney and thus excess phenylalanine and phenylpyruvicacid enters cerebrospinal fluid and then the brain causing severe mental retardation.

17. .. Phenylketonuria (Pku)

18. ….Phenylketonuria(PKU)Phenylketonuria - Genetics Home Reference Unable to metabolize phenylalanine

19. If Untreated in Infants: • Severe brain damage • Epilepsy • Behavioral Problems • Stunted growth • Symptoms Throughout Life if Treatment is not Followed Closely: • Musty body odor • Increased muscle tone • Fair skin and eyes • Vomiting & Active muscle tendon reflexes ….Symptoms and Effects of PKU

20. ..The Future of PKU • Due to the large amount of research done in Phenylketonuria patients can live a normal life while adhering to a strict protein-free diet • Research is still being done to determine if there is a better biochemical model for the effects of PKU on the body • If more detailed biochemical pathways of the effects of PKU can be determined there may be a method of introducing necessary chemical properties into the body, preventing some of the long term effects of PKU.

21. Sickle Cell Anemia

22. …Symptoms of Sickle Cell Anemia & Complications • Fatigue • Pain Crisis • Dactylitis and Arthritis • Bacterial Infections • Splenic Sequestration • Lung and Heart Damage • Leg Ulcers • Aseptic Necrosis and Bone Infarcts • Eye Damage • Jaundice • Acute Chest Syndrome

23. …Current Research and Treatments of Sickle Cell Anemia Treatments • Antibiotics • Pain-relieving Medications • Supplemental Oxygen • Blood Transfusions • Health maintenance starts with early diagnosis

24. Cystic Fibrosishttp://www.cff.org/home • An inherited disease that affects sodium channels in the body and causes respiratory and digestive problems.

25. …Cystic Fibrosis • There is no cure for Cystic Fibrosis and treatment can slow progression of the disease • One in 25 people carry the gene but will have no symptoms • CF is usually diagnosed at birth • CF is not contagious • CF occurs in males and females.

26. …Effects of Cystic Fibrosis • Excessive production of thick, sticky mucus in the airways • Affects tissues in the airway, gastrointestinal tract, ducts of the pancreas, the bile ducts of the liver, and the male urogenital tract • Causes difficultly clearing infections and can result in lung damage over a period of time.

27. …Symptoms of Cystic Fibrosis • Persistent cough, with great physical effort • Some difficulty breathing • Tiredness, lethargy or an impaired exercise ability • Frequent visits to the toilet • Salt loss in hot weather which may produce muscle cramps or weakness • Poor appetite.

28. Caused by genetic mutation in a single gene on chromosome 7 Gene contains building info for CFTR Mutation causes a CFTR that won’t open. …Genetic Information Cystic Fibrosis

29. …Treatments of Cystic Fibrosis • Chest physiotherapy • Antibiotics • Inhalations via a compressed air pump and nebuliser • Enzyme replacement capsules with meals and snacks • A well balanced diet high in protein, fat and kilojoules • Supplementary vitamins • Salt supplements • Regular exercise.

30. Down Syndrome • Down syndrome is caused by an extra chromosome present on chromosome 21 • Down syndrome is caused by mutations • Forms of Down syndrome • Klinefelter’s disease • Turner’s syndrome • Philadelphia chromosome • A genetic form of Down syndrome: • Mosaicism

31. …Individuals with Down Syndrome

32. AlzheimersAlzheimer's Association | Home • Alzheimers is a form of dementia that causes changes in the brain, and affects a person’s memory, mood, and behavior. • Disease mostly affects people over 65. • Diagnosis: • There is no specific test for Alzheimer’s disease, however, physician are able to look at a person’s medical history, do a complete physical or give a memory and/or psycological test to see how well the brain works. • Brain scan.

33. Severe Combine Immunodeficiency (SCID, X-SCID)http://www.bt.cdc/gov/training/smallpoxvaccine/reactions/prog_vac_viewall.html

34.  Diseased Pancreatic Tissue Type I Diabeteshttp://www.diabetes.org/home.jsp

35. ACHONDROPLASIADefined as a bone growth disorder characterized by abnormal body proportions

36. Autism • Severe disorder from an array of the Autism Spectrum Disorders (ASD) • Another common form of ASD is Asperger Syndrome • Developmental disorder affects parts of brain, notably the amagdala, hippocampus, and cerebellum • immune system, and gastrointestinal tract • 1 out of 150 people are affected • More prevalent in males than in females.

37. …Characteristics of Autism • difficulties with social interaction • problems with verbal and nonverbal communication • repetitive behaviors or narrow, obsessive interests • behaviors can range in impact from mild to disabling.

38. …Causes of Autism • Complex,polygenic and multifactoral • Highly heritable • Gene-environment interaction • Vaccines.

39. Rapidly Changing world Changes in availability of resources Changes in longevity

40. ..Rapidly Changing world • Changes in climate • Changes in transits

41. Future Treatments • Stem Cells • Gene Therapies • Advanced IVF Techniques • Therapeutic Cloning

42. ..Adult Stem Cells • Stem cell collected from adult can be harvested from many area including the bone marrow. • Alternative to Embryonic Stem cells • Potential to reverse and cure Diabetes

43. ..Embryonic Stem Cells • Use undifferentiated cell from embryos and cultures them to grow into need cells • Many ethical and social concerns surrounding this research • Neurons Grown from Embryonic Stem Cells Restore Function in Paralyzed Rats • Hold potential cures for 1000s of diseases many genetic disorders.

44. Advanced IVF Techniques • This treatment is aimed at women who would pass on a genetic defect to the child. • Also helps women who suffer with mitochondria disease. • Faulty genes are removed from the embryo , and replaced by healthy genes from the additional woman.

45. ..Therapeutic Cloning • Using stem cells to replace or create tissues and organs • Currently heart tissues and full bladders are being grow in lab • Fig. Stem cell treatments and tissues recreated in the heart of a child

46. Summary There are four types of Genetic Disorders: Single gene, Multifactorial, Chromosomal, Mitochondria • Heredity plays a big role in GD • Phenotype is genes being express as characteristic • Genotype is all the gene present in the genome • Evolution needs mutations to adapt organism which is essential for survival • GD are mutations that had some kind “fitness” for the organism and get promoted to the next generation. • GD are apart of our adaptations to environments, but as the world changes rapidly GD become added problems in a complex world. • Scientists are working on treatment that can cure, reverse, prevent and remove GD from individual. • GD will always be apart of our species but the future hold promising way to suppress the damaging effects of GD.

47. Refereces: • National Institute of Diabetes, Digestive, and Kidney Diseases, NIH Publication No. 97-4200, July 1997, e-text posted: 12 Feb 1998. • Baz R, Mekhail T. Clotting Factor Deficiencies. The Cleveland Clinic. Reviewed July 15, 2004. Available at: https://www.clevelandclinicmeded.com/diseasemanagement/hematology/ clotting/clotting.htm. Accessed April 1, 2006. • Bicker B, Kwiatkowski JL. Coagulation disorders. In: Dipiro JT, Talbert RL, Yee GC, et al. (eds.). Pharmacotherapy: a Pathophysiologic Approach. 5th ed. New York: McGraw Hill; 2002. • Griffin M.D., Gregory C. Hemophilia. Teens Health, Nemours Foundation. Available at: http://kidshealth.org/teen/diseases_conditions/blood/hemophilia.html. Accessed April 4, 2006. • Peter Turnpenny, Sian Ellard. Emery’s Elements of Medical Genetics, textbook 12th Edition, Chapter 11 • Dr. Estella Chen. Lecture notes from Medical Genetics. Located on WebCT based on Metabolic Disorders • “Living with PKU”, Published by Inherited Metabolic Disease Clinic, University of Colorado. http://www.medhelp.org/lib/pku.htm • Phenylketonuria. Genetic Science Learning Center, University of Utah, 2006. http://gslc.genetics.utah.edu/units/disorders/whataregd/pku/index.cfm • The Genetic Disease Phenylketonuria. Melissa G. Price, Department of Biology, Missouri State Western University 2006. http://clearinghouse.missouriwestern.edu/manuscripts/159.asp • The History of Newborn Phenylketonuria Screening in the U.S.. Diane B. Paul, University of Massachusetts. The Medical and Public Health Law Site. file:///E:/pku%20screening%20history.htm • Bowman-Kruhm, Mary. Everything You Need to Know About Down Syndrome. New York: Rosen Publishing Group, 2000. • Edelson, Edward. Genetics and Heredity. New York: Chelsea House Publishers, 1990. • Tocci, Salvatore. Down Syndrome. Danbury: Grolier Publishing, 2000.

48. References ……………………………. • Lieberman, Abraham. “ The New Genetics of Parkinson Disease: Is Parkinson • Disease Inherited?” National Parkinson Foundation. April 08, 2006. http://www.parkinson.org/site/apps/s/content.asp?c=9dJFJLPwB&b=108269&ct=89702 . • “Parkinson Primer”. National Parkinson Foundation. April 1, 2006. • http://www.parkinson.org/site/pp.asp?c=9dJFJLPwB&b=71354. • “Parkinson Overview.” Health A to Z. April 1, 2006. • http://www.healthatoz.com/healthatoz/Atoz/dc/caz/neur/park/parkwhat.jsp. • “Specific Genetic Disorders.” National Human Genome Research Institute. March 28, • 2006. http://www.genome.gov/10001204. • “Two types of Parkinson’s”. BBC News. March 28, 2006. • http://news.bbc.co.uk/1/hi/health/263798.stm. • “Types of Parkinson’s Diseases”. Mayo Clinic. April 1, 2006. • http://www.mayoclinic.org/parkinsons-disease/types.html. • “What are Genetic Disorders?”. Genetic Science Learning Center. April 1, 2006. • http://gslc.genetics.utah.edu/units/disorders/whataregd/ • Brooker, Robert. Genetics: Analysis and Princeples; McGraw-Hill Higher Education: Columbus, OH, 2005. • Campbell, Neil A. Biology: Sixth Edition; Pearson Education Inc.: San Francisco, CA, 2002. • Charache, S. et al. “Effects of Hydroxyurea on the Frequency of Painful Crisis in Sickle Cell Anemia.” New England Journal of Medicine. 332 (1995):1317-22. • Freeman, Scott, and Jon C. Herron. Evolutionary Analysis: Third Edition; Pearson Education, Inc.: Upper Saddle River, NJ, 2004; pp. 112-13. • “Sickle Cell Disease.” Encyclopedia of Genetic Disorders. Ed. Stacey L. Blackford. Thomson Gale, 2002. eNotes.com. 2006. 10 April 2006<http://health.enotes.com/genetic-disorders-encyclopedia/sickle- cell-disease>

49. ………….References • Multifactorial • http://images.google.com/imgres?imgurl=http://www.holimedex.com/Breast%2520Cancer%2520Cell.jpg&imgrefurl=http://wfth.wordpress.com/2007/11/28/cancer-update-from-john-hopkins/&h=400&w=500&sz=15&hl=en&start=16&sig2=R5GG7L9CwzWK966x1pHBiQ&usg=__d5cRFZh5ob8JLWunfnt3xexyOms=&tbnid=X70B7VRyDI4HrM:&tbnh=104&tbnw=130&ei=VrIMScbbFo70sAPPytmKDw&prev=/images%3Fq%3Dcancer%2Bcells%26gbv%3D2%26ndsp%3D20%26hl%3Den%26sa%3DX • http://images.google.com/imgres?imgurl=http://www.endotext.org/obesity/obesity8/figures8/figure1.jpg&imgrefurl=http://www.endotext.org/obesity/obesity8/obesity8.htm&h=493&w=400&sz=17&hl=en&start=13&sig2=L-YktcgPFslasHTNZhXNdQ&usg=__6LjOH4GwAhM83DtYQrtwszjbky4=&tbnid=BmyJBVFLCNzX_M:&tbnh=130&tbnw=105&ei=X74MSYnUAouasAPD_qSODw&prev=/images%3Fq%3DPima%2BIndians%2Bobesity%26gbv%3D2%26hl%3Den • http://images.google.com/imgres?imgurl=http://www.endotext.org/obesity/obesity8/figures8/figure1.jpg&imgrefurl=http://www.endotext.org/obesity/obesity8/obesity8.htm&h=493&w=400&sz=17&hl=en&start=13&sig2=EXyWShDi9ncJAn4SYGUTcg&usg=__-gtasynSzLE_6TokrNkLzLkzsq0=&tbnid=BmyJBVFLCNzX_M:&tbnh=130&tbnw=105&ei=IMcMSZyEOouasAOy_qSODw&prev=/images%3Fq%3DPima%2BIndians%2Bobesity%26gbv%3D2%26hl%3Den • Chromosomal http://images.google.com/imgres?imgurl=http://www.downssupport.org.uk/images/down%27schild2.jpg&imgrefurl=http://www.downssupport.org.uk/aboutdowns.html&h=300&w=300&sz=62&hl=en&start=9&sig2=KTzWqN-jFLt6HNlNiS2unQ&usg=__96KU4srG3W7jAlRuk50mtj53stE=&tbnid=UvrsIOO7dGQoBM:&tbnh=116&tbnw=116&ei=JsgMSfe3I5WUsAPBr-2TDw&prev=/images%3Fq%3Ddown%2Bsyndrome%26gbv%3D2%26hl%3Den%26sa%3DX

50. ………….References • Mitochondrial • ://images.google.com/imgres?imgurl • =http://www.mda.org/publications/images/q64bigmito.jpg&imgrefurl=http://www.mda.org/publications/Quest/q64mito.html&h=383&w=343&sz=37&hl=en&start=15&sig2=FONq0Ahe_pPkbEBSCjN3Ow&usg=__UMgn6S8srDJHjG4YM2mH8K_mpkk=&tbnid=z_YJ9MPEb9RrEM:&tbnh=123&tbnw=110&ei=rl4LSa2PCZTysAOI2PiYDw&prev=/images%3Fq%3DMitochondrial%2Bmyopathies%26gbv%3D2%26hl%3Den%26sa%3DG • http://images.google.com/imgres?imgurl=http://www.specialchild.com/archives/poster-child077.jpg&imgrefurl=http://ww • w.specialchild.com/archives/dz-039.html&h=224&w=168&sz=18&hl=en&start=9&sig2=-aZSiy2oR8j0opJ9Abpm1A&usg=__V5orNGqztPGVNP1utIQ-S1Y5U7I=&tbnid=z7zlyK-Sl_QTEM:&tbnh=108&tbnw=81&ei=rl4LSa2PCZTysAOI2PiYDw&prev=/images%3Fq%3DMitochondrial%2Bmyopathies%26gbv%3D2%26hl%3Den%26sa%3DG • http://images.google.com/imgres?imgurl=http://www.ntfactor.com/Images/mitoman.gif&imgrefurl=http://www.ntfactor.com/mitoman.html&h=393&w=432&sz=32&hl=en&start=14&sig2=H6_OXmykPGH532_uvurDjg&usg=__EFrAA9bjfKHeHeyLZfh6Lvt5nco=&tbnid=6WhqPmESiYFqxM:&tbnh=115&tbnw=126&ei=lNAMSfrZFZWUsAO2r-2TDw&prev=/images%3Fq%3DMitochondrial%2Bmyopathies%26gbv%3D2%26hl%3Den%26sa%3D • Evolutionary Advantage • http://www.answersingenesis.org/tj/v17/i1/DNA.asp