Genomics and Me:Living with a Cystic Fibrosis

Family

S. CarlsonBL 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– 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

Lyn Carlson – Age 17 and Doing Well!

Questions?

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