Genetic Disorders

1
Genetic Disorders

Chapter 11 Contd.AS SUPPLIMENT
2
Common diseases of Genetic order

• Gaucher Disease
• Huntingtons Disease
• Hemophilia
• Parkinsons Disease
• Phenylketonuria
• Sickle Cell Anemia
• Cystic Fibrosis
• Down Syndrome
• Alzheimers 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
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,
  ß-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
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.

7
Huntingtons Disease

• Huntingtons 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 Huntingtons 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.

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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
Parkinsons Disease

• Parkinson s disease is a neurological condition
  that has a genetic component next to Alzheimers.
  
• The chance of getting or developing Parkinsons
  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 Parkinsons 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
  phenylpyruvic acid enters cerebrospinal fluid and
  then the brain causing severe mental retardation.

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.. Phenylketonuria (Pku)
18
.Phenylketonuria(PKU)Phenylketonuria - Genetics
Home Reference
Unable to metabolize phenylalanine
19
.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

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.

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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.

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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.

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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 wont open.

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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.

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Down Syndrome

• Down syndrome is caused by an extra chromosome
  present on chromosome 21
• Down syndrome is caused by mutations
• Forms of Down syndrome
• Klinefelters disease
• Turners syndrome
• Philadelphia chromosome
• A genetic form of Down syndrome
• Mosaicism

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Individuals with Down Syndrome

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AlzheimersAlzheimer's Association
Home

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

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Severe Combine Immunodeficiency (SCID,
X-SCID)http//www.bt.cdc/gov/training/smallpoxvac
cine/reactions/prog_vac_viewall.html
34
Type I Diabeteshttp//www.diabetes.org/
home.jsp

• ? Diseased Pancreatic Tissue

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 transits

• Changes in climate

41
Future Treatments

• Stem Cells
• Gene Therapies
• Advanced IVF Techniques
• Therapeutic Cloning

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..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.h
  tm. 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/blo
  od/hemophilia.html. Accessed April 4, 2006.
• Peter Turnpenny, Sian Ellard. Emerys 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.uta
  h.edu/units/disorders/whataregd/pku/index.cfm
• The Genetic Disease Phenylketonuria. Melissa G.
  Price, Department of Biology, Missouri State
  Western University 2006. http//clearinghouse.miss
  ouriwestern.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/pku20screening20history.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?c9dJFJLPwBb108269c
  t89702 .
• Parkinson Primer. National Parkinson
  Foundation. April 1, 2006.
• http//www.parkinson.org/site/pp.asp?c9dJFJLPwBb
  71354.
• Parkinson Overview. Health A to Z. April 1,
  2006.
• http//www.healthatoz.com/healthatoz/Atoz/dc/caz/n
  eur/park/parkwhat.jsp.
• Specific Genetic Disorders. National Human
  Genome Research Institute. March 28,
• 2006. http//www.genome.gov/10001204.
• Two types of Parkinsons. BBC News. March 28,
  2006.
• http//news.bbc.co.uk/1/hi/health/263798.stm.
• Types of Parkinsons Diseases. Mayo Clinic.
  April 1, 2006.
• http//www.mayoclinic.org/parkinsons-disease/types
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• What are Genetic Disorders?. Genetic Science
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• http//gslc.genetics.utah.edu/units/disorders/what
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• Brooker, Robert. Genetics Analysis and
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• Campbell, Neil A. Biology Sixth Edition Pearson
  Education Inc. San Francisco, CA, 2002.

49
.References

• Multifactorial
• http//images.google.com/imgres?imgurlhttp//www.
  holimedex.com/Breast2520Cancer2520Cell.jpgimgre
  furlhttp//wfth.wordpress.com/2007/11/28/cancer-u
  pdate-from-john-hopkins/h400w500sz15hlens
  tart16sig2R5GG7L9CwzWK966x1pHBiQusg__d5cRFZh5
  ob8JLWunfnt3xexyOmstbnidX70B7VRyDI4HrMtbnh10
  4tbnw130eiVrIMScbbFo70sAPPytmKDwprev/images
  3Fq3Dcancer2Bcells26gbv3D226ndsp3D2026hl3D
  en26sa3DX
• http//images.google.com/imgres?imgurlhttp//www.
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  imgrefurlhttp//www.endotext.org/obesity/obesity
  8/obesity8.htmh493w400sz17hlenstart13si
  g2L-YktcgPFslasHTNZhXNdQusg__6LjOH4GwAhM83DtYQr
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  2BIndians2Bobesity26gbv3D226hl3Den
• http//images.google.com/imgres?imgurlhttp//www.
  endotext.org/obesity/obesity8/figures8/figure1.jpg
  imgrefurlhttp//www.endotext.org/obesity/obesity
  8/obesity8.htmh493w400sz17hlenstart13si
  g2EXyWShDi9ncJAn4SYGUTcgusg__-gtasynSzLE_6TokrN
  kLzLkzsq0tbnidBmyJBVFLCNzX_Mtbnh130tbnw105
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• Chromosomal
• http//images.google.com/imgres?imgurlhttp//www.
  downssupport.org.uk/images/down27schild2.jpgimgr
  efurlhttp//www.downssupport.org.uk/aboutdowns.ht
  mlh300w300sz62hlenstart9sig2KTzWqN-jFL
  t6HNlNiS2unQusg__96KU4srG3W7jAlRuk50mtj53stEtb
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  5WUsAPBr-2TDwprev/images3Fq3Ddown2Bsyndrome2
  6gbv3D226hl3Den26sa3DX

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.References

• Mitochondrial
• //images.google.com/imgres?imgurl
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  .jpgimgrefurlhttp//www.mda.org/publications/Que
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  ig2FONq0Ahe_pPkbEBSCjN3Owusg__UMgn6S8srDJHjG4YM
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  0eirl4LSa2PCZTysAOI2PiYDwprev/images3Fq3DMit
  ochondrial2Bmyopathies26gbv3D226hl3Den26sa3
  DG
• http//images.google.com/imgres?imgurlhttp//www.
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  efurlhttp//ww
• w.specialchild.com/archives/dz-039.htmlh224w16
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• http//images.google.com/imgres?imgurlhttp//www.
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  l3Den26sa3D
• Evolutionary Advantage
•  http//www.answersingenesis.org/tj/v17/i1/DNA.asp