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Genetic Disorders Chapter 11 Contd. AS SUPPLIMENT
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
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.
Gaucher Disease 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, βglucocerebrosidase. 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.
…General Signs and Symptoms bone pain and fractures easy bruising fatigue seizures Liver and spleen enlargement
…Gaucher Disease 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.
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.
…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.
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.
. . 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.
. . 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.
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.
…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.
…. ONGOING RESEARCH Parkinson • Nearly $70 million in research programs funded • Michael J. Fox Foundation. • National Parkinson Foundation.
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 phenylpyruvic acid enters cerebrospinal fluid and then the brain causing severe mental retardation.
. . Phenylketonuria (Pku)
…. Phenylketonuria(PKU) Phenylketonuria - Genetics Home Reference Unable to metabolize phenylalanine
…. Symptoms and Effects of PKU 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
. . 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.
Sickle Cell Anemia
…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
…Current Research and Treatments of Sickle Cell Anemia Treatments › Antibiotics › Pain-relieving Medications › Supplemental Oxygen › Blood Transfusions › Health maintenance starts with early diagnosis
Cystic Fibrosis http: //www. cff. org/home An inherited disease that affects sodium channels in the body and causes respiratory and digestive problems.
…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.
…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.
…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.
…Genetic Information Cystic Fibrosis 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.
…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.
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
…Individuals with Down Syndrome
Alzheimers Alzheimer'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.
Severe Combine Immunodeficiency (SCID, XSCID) http: //www. bt. cdc/gov/training/smallpoxvaccine/reactions/prog_vac_viewall. html
Type I Diabetes http: //www. diabetes. org/home. jsp Diseased Pancreatic Tissue
ACHONDROPLASIA Defined as a bone growth disorder characterized by abnormal body proportions
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.
…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.
…Causes of Autism Complex, polygenic and multifactoral › Highly heritable › Gene-environment interaction Vaccines.
Rapidly Changing world Changes in longevity Changes in availability of resources
. . Rapidly Changing world Changes in transits n. Changes in climate
Future Treatments Stem Cells Gene Therapies Advanced IVF Techniques Therapeutic Cloning
. . 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
. . 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 1000 s of diseases many genetic disorders.
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.
. . 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
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.
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…………. References 1. 2. 3. 4. 5. 1. Mitochondrial : //images. google. com/imgres? imgurl =http: //www. mda. org/publications/images/q 64 bigmito. jpg&imgrefurl=http: //ww w. mda. org/publications/Quest/q 64 mito. html&h=383&w=343&sz=37&hl=en&st art=15&sig 2=FONq 0 Ahe_p. Pkb. EBSCj. N 3 Ow&usg=__UMgn 6 S 8 sr. DJHj. G 4 YM 2 m. H 8 K_mpkk=&tbnid=z_YJ 9 MPEb 9 Rr. EM: &tbnh=123&tbnw=110&ei=rl 4 LSa 2 PCZTys. AOI 2 Pi. YDw&prev=/images%3 Fq%3 DMitochondrial%2 Bmyopathies %26 gbv%3 D 2%26 hl%3 Den%26 sa%3 DG http: //images. google. com/imgres? imgurl=http: //www. specialchild. com/archives/ poster-child 077. jpg&imgrefurl=http: //ww w. specialchild. com/archives/dz 039. html&h=224&w=168&sz=18&hl=en&start=9&sig 2=a. ZSiy 2 o. R 8 j 0 op. J 9 Abpm 1 A&usg=__V 5 or. NGqzt. PGVNP 1 ut. IQS 1 Y 5 U 7 I=&tbnid=z 7 zly. KSl_QTEM: &tbnh=108&tbnw=81&ei=rl 4 LSa 2 PCZTys. AOI 2 Pi. YDw&prev=/ima ges%3 Fq%3 DMitochondrial%2 Bmyopathies%26 gbv%3 D 2%26 hl%3 Den%26 sa %3 DG http: //images. google. com/imgres? imgurl=http: //www. ntfactor. com/Images/mito man. gif&imgrefurl=http: //www. ntfactor. com/mitoman. html&h=393&w=432&sz =32&hl=en&start=14&sig 2=H 6_OXmyk. PGH 532_uvur. Djg&usg=__EFr. AA 9 bjf KHe. Hey. LZfh 6 Lvt 5 nco=&tbnid=6 Whq. Pm. ESi. YFqx. M: &tbnh=115&tbnw=126& ei=l. NAMSfr. ZFZWUs. AO 2 r 2 TDw&prev=/images%3 Fq%3 DMitochondrial%2 Bmyopathies%26 gbv%3 D 2% 26 hl%3 Den%26 sa%3 D Evolutionary Advantage http: //www. answersingenesis. org/tj/v 17/i 1/DNA. asp