Genomics and Me: Living with a Cystic Fibrosis Family S. Carlson BL 3300 06 December 2002
Dec 19, 2015
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– 1 in ~200 births
Graphic Source: Welsh, Michael J., and Smith, Alan E. Scientific American, December 1995 http://www.people.virginia.edu/~rjh9u/cfsciam.htmc
Gene discovered in 1989
Dr. Lap-Chee Tsui Dr. Jack Riordan Chromosome 7 Cystic Fibrosis
Transmembrane Conductance Regulator (CFTR)
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
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 volume-absorbing
epithelia due to increase in Na+ channel activity
Results– 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
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
– 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
References NCBI The Human Gene Map http://www.ncbi.nlm.nih.gov/cgi-bin/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