Transcript Genetic Disorders - Faculty Web Pages

Chapter 11 Contd.AS
SUPPLIMENT














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
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 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.






bone pain and
fractures
easy bruising
fatigue
seizures
Liver and spleen
enlargement
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.

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.



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.
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 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.

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.
•Nearly $70 million in research programs funded
•Michael J. Fox Foundation.
•National Parkinson Foundation.
•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.
Downloaded from: StudentConsult (on 10 February 2006 10:40
PM)
Unable to metabolize phenylalanine
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
•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.











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
Treatments
› Antibiotics
› Pain-relieving Medications
› Supplemental Oxygen
› Blood Transfusions
› Health maintenance starts with early
diagnosis

An inherited disease
that affects sodium
channels in the body
and causes respiratory
and digestive problems.





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.
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.







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.
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.









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 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
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.


 Diseased Pancreatic
Tissue
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.

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.


Complex,polygenic
and multifactoral
› Highly heritable
› Gene-environment
interaction

Vaccines.
Changes in longevity
Changes in availability of
resources

Changes in transits
Changes
in climate

Stem Cells

Gene Therapies

Advanced IVF Techniques

Therapeutic Cloning
•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
•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.
•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.
•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
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.













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.
…………………………….



















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/geneticdisorders-encyclopedia/sicklecell-disease>
Multifactorial
http://images.google.com/imgres?imgurl=http://www.holimedex.com/Breast%2520Cancer%2520
Cell.jpg&imgrefurl=http://wfth.wordpress.com/2007/11/28/cancer-update-from-johnhopkins/&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
2.
http://images.google.com/imgres?imgurl=http://www.endotext.org/obesity/obesity8/figures8/figur
e1.jpg&imgrefurl=http://www.endotext.org/obesity/obesity8/obesity8.htm&h=493&w=400&sz=1
7&hl=en&start=13&sig2=LYktcgPFslasHTNZhXNdQ&usg=__6LjOH4GwAhM83DtYQrtwszjbky4=&tbnid=BmyJBVFLCN
zX_M:&tbnh=130&tbnw=105&ei=X74MSYnUAouasAPD_qSODw&prev=/images%3Fq%3DPi
ma%2BIndians%2Bobesity%26gbv%3D2%26hl%3Den
3.
http://images.google.com/imgres?imgurl=http://www.endotext.org/obesity/obesity8/figures8/figur
e1.jpg&imgrefurl=http://www.endotext.org/obesity/obesity8/obesity8.htm&h=493&w=400&sz=1
7&hl=en&start=13&sig2=EXyWShDi9ncJAn4SYGUTcg&usg=__gtasynSzLE_6TokrNkLzLkzsq0=&tbnid=BmyJBVFLCNzX_M:&tbnh=130&tbnw=105&ei=IMc
MSZyEOouasAOy_qSODw&prev=/images%3Fq%3DPima%2BIndians%2Bobesity%26gbv%3D
2%26hl%3Den
 Chromosomal
http://images.google.com/imgres?imgurl=http://www.downssupport.org.uk/images/down%27schild2.jp
g&imgrefurl=http://www.downssupport.org.uk/aboutdowns.html&h=300&w=300&sz=62&hl=en
&start=9&sig2=KTzWqNjFLt6HNlNiS2unQ&usg=__96KU4srG3W7jAlRuk50mtj53stE=&tbnid=UvrsIOO7dGQoBM:&tb
nh=116&tbnw=116&ei=JsgMSfe3I5WUsAPBr2TDw&prev=/images%3Fq%3Ddown%2Bsyndrome%26gbv%3D2%26hl%3Den%26sa%3DX

1.

1.
2.
3.
4.
5.

1.
Mitochondrial
://images.google.com/imgres?imgurl
=http://www.mda.org/publications/images/q64bigmito.jpg&imgrefurl=http://ww
w.mda.org/publications/Quest/q64mito.html&h=383&w=343&sz=37&hl=en&st
art=15&sig2=FONq0Ahe_pPkbEBSCjN3Ow&usg=__UMgn6S8srDJHjG4YM2
mH8K_mpkk=&tbnid=z_YJ9MPEb9RrEM:&tbnh=123&tbnw=110&ei=rl4LSa
2PCZTysAOI2PiYDw&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/dz039.html&h=224&w=168&sz=18&hl=en&start=9&sig2=aZSiy2oR8j0opJ9Abpm1A&usg=__V5orNGqztPGVNP1utIQS1Y5U7I=&tbnid=z7zlyKSl_QTEM:&tbnh=108&tbnw=81&ei=rl4LSa2PCZTysAOI2PiYDw&prev=/ima
ges%3Fq%3DMitochondrial%2Bmyopathies%26gbv%3D2%26hl%3Den%26sa
%3DG
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&sig2=H6_OXmykPGH532_uvurDjg&usg=__EFrAA9bjf
KHeHeyLZfh6Lvt5nco=&tbnid=6WhqPmESiYFqxM:&tbnh=115&tbnw=126&
ei=lNAMSfrZFZWUsAO2r2TDw&prev=/images%3Fq%3DMitochondrial%2Bmyopathies%26gbv%3D2%
26hl%3Den%26sa%3D
Evolutionary Advantage
http://www.answersingenesis.org/tj/v17/i1/DNA.asp