Transcript Genomics and Me: Living with a Cystic Fibrosis Family S. Carlson

Genomics and Me:
Living with a Cystic Fibrosis
Family
S. Carlson
BL 3300
06 December 2002
What is Cystic Fibrosis?
Also called CF
 Autosomal recessive inherited disorder
 Affects respiratory, digestive, and
reproductive systems
 1 in ~2000 births
 Most common lethal genetic disease in
Caucasions
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– 1 in ~200 births
Graphic Source: Welsh, Michael J.,
and Smith, Alan E. Scientific
American, December 1995
http://www.people.virginia.edu/~rj
h9u/cfsciam.htmc
Gene discovered in
1989
 Dr. Lap-Chee Tsui
 Dr. Jack Riordan
 Chromosome 7
 Cystic Fibrosis
Transmembrane
Conductance
Regulator (CFTR)
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Graphic Source: NCBI The Human Gene Map
http://www.ncbi.nlm.nih.gov/cgi-bin/SCIENCE96/gene?CFTR
CFTR Gene
Long arm of
chrom 7
 Over 6000
nucleotides
 Spread over
27 exons
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Graphic Source: “CF Pictures”
http://personal.nbnet.nb.ca/normap/cfpictures.htm
One Amino Acid
Since discovery of CFTR in 1989, over
900 mutations associated with CF
 Most common: deletion of one
phenylalanine residue at position 508
(F508)
 Accounts for 70% of all CF alleles
worldwide

Phenylalanine (f, Phe)
Graphic Source: www.chemfinder.com
What does CFTR do?

Regulates cAMP pumps
– Cl- channels
– Na+ / Cl- equilibrium
– Water balances concentration of Na+ and
Cl- across cell
– Fluid secretion
Mutated CFTR
In CF patients, Cl- channel regulated by
CFTR is closed
 Decrease of Cl- secretion
 Increase in Na+ transport in volumeabsorbing epithelia due to increase in Na+
channel activity
 Results
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– Thick sticky mucous in lungs
• Environment for bacteria to grow
– CFTR pumps in liver and pancreas also affected
My Family Tree
Graphic Source: “Facts About Cystic Fibrosis”
http://www.nhlbi.nih.gov/health/public/lung/other/cf.htm#what
CF in My Family
August 18, 1985 – Lyn Carlson born
 Colicky baby?
 Crying, no weight gain due to lack of
nutrition from food
 Diagnosed with cystic fibrosis

– 65 Roses?
Enzyme supplements
 Respiratory Therapy

Treatment

Preventative
– Postural drainage
– Positive expiratory pressure (PEP) mask
– Flutter valve
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Lung infection
– Vaccines
– Antibiotics
Enzyme Regulation
 Diet Regulation

Complication: CFRD
Cystic Fibrosis Related Diabetes
(CFRD)
 Depressed pancreatic insulin production

– Insulin injections
– Additional diet regulation
Complication: Depression
Adolescents deal with tough issues
 Lyn
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– Anorexia
– Bulemia
– Depression
– Feeling out of control of life

Symptoms aren’t published
Am I a Carrier?

Genetic counseling
 The “odds”
 Insurance discrimination
– Widespread confusion over difference between
being a carrier of a genetic disease and actually
having disease
– Few legal safeguards to protect genetic “carriers”
– Since then, legislation passed in some states
– Husband to be tested
Hope for a Cure

Gene therapy
– Introduce healthy CFTR gene into CF cells
– Virus (vector) introduces gene

Research has established that:
– Gene transfer is possible
– Expression of transferred gene is possible
in humans
– Expression sufficient to compensate for
CFTR deficiency
– Ebola, influenza may be promising leads

Some unanswered questions
Genomics and Me
Behavior as a child
 Choice of Michigan Tech
 Decision to have children
 Decision to become a doctor

Lyn Carlson – Age 17 and Doing Well!
Questions?
References
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NCBI The Human Gene Map http://www.ncbi.nlm.nih.gov/cgibin/SCIENCE96/gene?CFTR
Welsh, Michael J., and Smith, Alan E. Scientific American, December 1995
http://www.people.virginia.edu/~rjh9u/cfsciam.htmc
Bland, Amy, Gibson, Kevin, and Mayorga, Angela. Cystic Fibrosis.
http://medicine.creighton.edu/forpatients/CF/cf.html
CF Currents: At Home Edition. Winter 1994, Vol. 2, No. 1. McNeil
Pharmaceutical Co., Raritan, NJ.
CF Currents: At Home Edition. Fall 1997, Vol. 5, No. 3. McNeil
PharmaceuticalCo., Raritan, NJ.
“CF Pictures” http://personal.nbnet.nb.ca/normap/cfpictures.htm
Cystic Fibrosis Central Florida Support Group. CF Informer. Nov-Dec. 2000,
Vol. XIV, Orlando, FL.
Cystic Fibrosis Central Florida Support Group. CF Informer. Jan-Feb 1999, Vol.
X, Orlando, FL.
“Facts About Cystic Fibrosis”
http://www.nhlbi.nih.gov/health/public/lung/other/cf.htm#what
Orenstein, David M. Cystic Fibrosis: A Guide for Patient and Family.
1997.Lippincott-Raven Publishers, Philadelphia PA.
http://www.cysticfibrosis.com/
http://www.hum-molgen.de/bb/Forum7/HTML/000268.html
http://www.chemfinder.com