The Cystic Fibrosis Gene
Cystic fibrosis is an inherited autosomal recessive disease that exerts its main effects on the digestive system and the lungs. This disease is the most common genetic disorder amongst Caucasians. Cystic fibrosis affects about one in 2,500 people, with one in twenty five being a heterozygote. With the use of antibiotics, the life span of a person afflicted with CF can be extended up to thirty years however, most die before the age of thirteen.1 Since so many people are affected by this disease, it's no wonder that CF was the first human genetic disease to be cloned by geneticists. In this paper, I will be focusing on how the cystic fibrosis gene was discovered while at the same time, discussing the protein defect in the CF gene, the bio-chemical defect associated with CF, and possible treatments of the disease. Finding the Cystic Fibrosis Gene The classical genetic approach to finding the gene that is responsible for causing a genetic disease has been to first characterize the bio-chemical defect within the gene, then to identify the mutated protein in the gene of interest, and finally to locate the actual gene. However, this classical approach proved to be impractical when sea
One suggested treatment for CF has been to provide the missing chemicals to the epithelial cells. This can be accomplished by the addition of adenosine 3',5'-monophosphate (cAMP) or the addition of the nucleotide triphosphates ATP or UTP to cultures of nasal and tracheal epithelia. This has been proven to alter the rate of Cl- secretion by removing the 5-mmeter sol layer of fluid in the respiratory tract.9 Moreover, luminal application of the compound amiloride, which inhibits active Na+ absorption by blocking Na+ conductance in the apical membrane, reduced cell secretion and absorption to a steady state value.Another treatment that has been suggested is to squirt solutions of genetically engineered cold viruses in an aerosol form into the nasal passages and into the lungs of people infected with CF. This is done in hopes that the virus will transport corrected copies of the mutated gene into the affected person's airways so it can replace the mutated nucleotides.10 This form of treatment is known as gene therapy. A different approach taken in an attempt to cure cystic fibrosis involves correcting the disease while the affected "person" is still an embryo. Test tube fertilization (in vitro fertilization) and diagnosis of F508 during embryonic development can be accomplished through a biopsy of a cleavage-stage embryo, and amplification of DNA from single embryonic cells. 5 After this treatment, only unaffected embryos would be selected for implantation into the uterus. Affected embryo's would be discarded. Chloride conductance channels have dramatic potentials. One channel can conduct from 1x106 to 1x108 ions per second.8 This is particularly impressive when you consider the fact that there are not any channels present on cells to perform the required tasks. As a result of this, a mutation of one channel or even a partial mutation of a channel, that causes a decrease in the percentage of channel openings, can exert a major effect. Even the mildest of cures altering the Cystic Fibrosis Conductance Regulator in CF afflicted people would lead to significant improvements in that individuals health. Since cystic fibrosis is the most common genetic disorder, particularly amongst Caucasians, in today's society, intense research efforts towards its cure would be invaluable. When will cystic fibrosis be completely cured? No one can say for sure but, strong steps have already been taken towards reaching this goal. The isolated gene was proven to be responsible for causing CF by comparing its base pair sequence to the base pair sequence of the same sequence in a non-affected cell. The entire CF cDNA sequence is approximately 6,000 nucleotides long. In those 6,000 n.t.'s, three base pairs were found to be missing in affected cells, all three were in exon #10. This deletion results in the loss of a phenylalanine residue and it accounts for seventy percent of the CF mutations. In addition to this three base pair deletion pattern, up to 200 different mutations have been discovered in the gene accounting for CF, all to varying degrees. An inward, electrochemical Na+ gradient is generated by the Na+, K+-ATPase pump located in the basolateral membrane (the cell side facing the organ it is lining
Some common words found in the essay are:
CF RNA, ATP UTP, Defect Studies, Na+ H+-ATPase, Mutations NBF, Fibrosis Gene, Caucasians Cystic, Cystic Fibrosis, Francis Collins, Conclusion Chloride, cystic fibrosis, cf gene, base pairs, cell types, membrane spanning domain, blot electrophoresis, membrane spanning, spanning domain, fibrosis gene, cystic fibrosis gene, sweat glands, conductance regulator, fibrosis transmembrane conductance, common genetic disorder, southern blot electrophoresis,
Approximate Word count = 2162
Approximate Pages = 9 (250 words per page double spaced)
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