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 lethal genetic disorder in Caucasians, affecting one out of 2,500. On the bioethical front, CF was the first human genetic disease to be cloned by geneticists. The intent of this paper is to describe how the cystic fibrosis gene was identified, how the gene is defective, its physical manifestations, and to discuss possible treatments of the disease.
The classical approach to finding the gene that is responsible for causing a genetic disease is to first characterize the bio-chemical defect within the gene, then to identify the mutated protein in the gene, and finally to locate the actual gene. However, this classical approach proves to be impractical when searching for the CF gene. To find the gene responsible for CF, the principle of "reverse genetics" is applied. Scientists accomplish this by linking the disease to a specific chromosome. After this linkage, they isolate the gene of interest on the chromosome, and then test its product. Before the disease can be linked to a specific chromosome, however, a marker needs to be found that will always travel with the disease. This marker is known as a Restriction Fragment Length Polymorphism, or RFLP for short. RFLP's are varying base sequences of DNA in different individuals which are known to travel with genetic disorders. The RFLP for cystic fibrosis was first discovered through somatic cell hybridization (cell fusing) and southern blot electrophoresis (gel separation of DNA within an electric field). By using these techniques, three RFLP's were discovered for CF: Doc RI, J3.11, and Met. Utilizing hybridization (rapid heating and cooling of RNA with denatured DNA so that the RNA permanently associates with the DNA,) scientists discovered the CF gene to be located on the long arm of chromosome 7q. Soon after identifying these markers, another marker was discovered that frequented more ...
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...ides. This known as gene therapy.
A drastically different approach taken in an attempt to cure cystic fibrosis, performed as a method of preventive medicine, involves correcting the disease while the affected "person" is still an embryo. Test tube fertilization from affected parents and gene diagnosis during embryonic development can be accomplished through a biopsy of a cleavage-stage embryo and amplification of DNA from single embryonic cells. After this treatment, only unaffected embryos would be selected for implantation into the uterus. Unfortunately however, affected embryos would be discarded.
These treatments are all remarkable breakthroughs in medical science and provide geneticists with a highly positive outlook, but they are nowhere near the miracles yet to come with more research. Since cystic fibrosis is the most common lethal genetic disorder among Caucasians, intense research efforts towards better treatments and its cure are invaluable. The discoveries made from researching this disease may very well help the treatment or cure of other, unrelated diseases.
Modern molecular genetics has given hopes and heartaches to thousands of people around the world. These people are looking towards gene therapy for an answer to their questions. To some people such as NIH director Harold Varmus the answer is a better understanding of basic genetic research and to others the answer is a cure, a hope, that their lethal disease will someday be cured. This essay touches on the background of gene therapy for Cystic Fibrosis (CF), current social and ethical issues facing gene therapy for CF, and some thoughts on the importance of this controversial subject.
Francis S. Collins is a renowned geneticist who originally became Ph.D in Physical Chemistry at Yale University and later on, a Medical Doctor at University of North Carolina. As soon as he graduated he was offered a fellowship in Human Genetics at Yale University under the guidance of Sherman Weissman, currently Sterling Professor of Genetics. In the late 1980’s Collins became known in the field of Medical Genetics for his development of positional cloning, a technique that allows to locate a hereditary disease-causing gene by studying the inheritance pattern within a family. Working with his method researchers found the genes responsible for diseases like Cystic fibrosis, Huntington’s disease, Neurofibromatosis, Multiple Endocrine Neoplasia type one, and Hutchinson-Gilford Progeria Syndrome. In 1993 Dr. Collins succeeded Dr. James D. Watson as the director of the National Human Genome Research Institute (NHGRI), overseeing the role of the United States in the mapping of the human genome. In 2009 President Obama personally recommended Collins to lead the National Institute of Health (NIH) where he works until present day. Francis S. Collins is by no means a bragging individual, bits and pieces of his accomplishments are scattered throughout the book and he makes no big deal about it; instead he j...
Cystic Fibrosis is a lifelong disease that has a harsh negative affect on many vital organs, some of which include the lungs, pancreas, and intestines. This disease causes the mucus, tears, and sweat of the patient to be considerably thick. However, the thickness of such mucus is determined by the severity of the patient’s Cystic Fibrosis. This mucus affects the breathing of those diagnosed with cystic fibrosis, and many have reported an additional trouble with digesting food. One is most likely to have Cystic Fibrosis if their families have a history of such a disease. Therefore, Cystic Fibrosis is a genetic disease that is recessively passed down to proceeding generations. Additionally, this disease most commonly affects those who are Caucasian or of European descent.
Chronic illness can be very difficult to manage. Cystic fibrosis is the most common life-limiting autosomal (not sex-linked) recessive disease among Caucasian heritage. Although technically a rare disease, it is ranked as one of the most wide spread life-shortening genetic diseases. It is most common among nations in the Western world minus the exception of Finland but it is equally diagnosed between male and female.
Cystic Fibrosis is an autosomal recessive disease created by mutations in both copies of the cystic fibrosis transmembrane conductance regulator gene or the CFTR gene. This means a person must inherit the recessive gene from both parents to have cystic fibrosis. The CFTR gene codes for an ion channel protein that conducts chloride ions across the epithelial cell membranes of the passageways of the respiratory, digestive, and reproductive systems. Mutations of the transmembrane conductance regulator gene causes malfunctions of these chloride ion channels resulting in a decrease in fluid transport of affected organs leading to cystic fibrosis. These CFTR gene malfunctions are due to a lack of production, failure to reach its site of action due
While cystic fibrosis (CF) is not a new disease, there is still a lot to learn about it. In 1938 a pathologist, Dr Dorothy Andersen, provided the first clear description of cystic fibrosis. Before this time there had been reports of people that had the symptoms of someone with CF. During the seventeenth century children with the symptoms of CF were thought to be bewitched and their life expectancy was very short. Dr Dorothy Andersen gave this disease its name because cystic fibrosis refers to the scarring that is found on the pancreas. People with CF also have associated diseases like salt-loss syndrome, obstructive azoospermia, and gastrointestinal abnormalities. CF is inherited from one’s parents, making it a genetic disease. CF is caused by mutations in a certain gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This gene was first discovered in 1989 on chromosome pair 7. Cystic fibrosis is a recessive disease meaning both parents have to be a carrier. Whenever two CF carriers have a child together, there’s a 1 in 4 chance that their child will inherit the CF mutation. Although CF produces coughing it cannot be transmitted any other way than hereditary.
Cystic Fibrosis is an autosomal recessive genetic disease affecting the exocrine glands and progressively gets worse over time. The production of unusually thick mucus is formed causing blockages of the pancreatic ducts, intestines, and bronchi. Though it majorly affects the respiratory and digestive systems, sweat glands and the reproductive system are affected too. “The result is malnutrition, poor growth, numerous respiratory infections and breathing difficulties” (Interactive Health Tutorials: Medline Plus). Cystic Fibrosis affects almost 30,000 Americans: it affects males and females equally. There are another 12,000 people who carry the Cystic Fibrosis gene, and can pass it to offspring if they reproduce with someone with a like gene. Usually, a person is diagnosed with the disease as an infant. The life expectancy for a person with Cystic Fibrosis is, on average, thirty years. There is no cure for Cystic Fibrosis, but with treatments and supplements, people with the disease can live a normal life.
Cystic Fibrosis is caused by the mutation found on chromosome 7 on the CTFR protein. CTFR proteins function as a transportation of chloride ions in cells. When this mutation occurs, the lung airway lacks ions which prevents enough water coming through making thick mucus in the lungs which can create symptoms of lung infections and cough. Challenges include continuous efforts to be sanitary due to a weak immune system. People with cystic fibrosis must maintain a nutrient dense diet because there absorption of nutrients is so poor. Everyday they must go through several medical treatments such as inhalers and medications to keep their airways open. Matt, a Philadelphia native was first diagnosed with cystic fibrosis at the age of three. Six times
This disorder is less popular because it is an autosomal recessive disease. This basically means that a person needs two recessive traits in order to obtain the disease. Both genes from each of the parents have to be recessive in order for one to get CF. Both males and females can acquire the disease or inherit it. The mutation of the disease lies on the 7th chromosome and there have been over 1000 different mutations that have been scientifically discovered. Triangle-F508 is the most common mutation of the disorder. Over 2/3’s of the worldwide population that have Cystic Fibrosis is from this mutation. That is an incredibly large amount of people who suffer through this disease. Fortunately this disease is not contagious (hereditary) and there have not been any major outbreaks of this disease. However, the largest population of people with CF is in Europe.
The gene is found on the seventh chromosome in humans and contains 27 DNA sequences encoding 1,480 amino acids (Genetics). They found that the genetic change of this gene occurs through various mutations in the Cystic Fibrosis transmembrance conductance regulator or CTFR gene. Today 1,200 mutations are so far known. However, 70% of cystic fibrosis cases are caused by a single mutation, this mutation causes a deletion an amino acid at position 508 in the CTFR gene (Genetics). Once deleted the CTFR protein folds improperly and breaks down shortly after being made. Ultimately, every mutation affects the genes normal function as a channel protein. The CTFR gene crosses the membrane of many cell types, which is why the disease is referred to as a multisystem condition (Cystic). These cells are in charge of producing sweat, saliva, and tears. Its target is chloride ions whose movement in and out of the cell regulates the concentration of water in the tissue (Cystic). The movement of water is so crucial because it is responsible for keeping the mucus in our bodies thin and freely moving. So when mutations occur to this channel protein the flow of chloride ions is disrupted ultimately leading to the build up of thick damaging mucus associated with the disease
The CFTR gene is a transporter gene that contains codes that tells cells how to behave. It is also located in the seventh chromosome, in which it’s responsible for regulating salt and water movement between cells. When the CFTR gene contains a mutation, which is being prevented from doing its job, cystic fibrosis occurs. There are about 1500 CFTR mutations in six different categories, which are known to have a cause to cystic fibrosis, although each category of mutations affects the CTFR gene in a different way. The mutation causes a change in the code, so sodium and chloride doesn’t flow properly across the cell membrane. This results in the mucus becoming thick and sticky, which causes problems to people with cystic fibrosis (Alma).
A person is either a carrier of the defective CF gene, not a carrier of the CF gene, or will have cystic fibrosis. If a person has cystic fibrosis that means that the defective CF gene was received from each parent. If a person does not have two defective CF genes but does have one defective CF gene then he/she is a carrier of cystic fibrosis. There are more than seventy thousand people leaving with this disease worldwide, and most are diagnosed by the age of just two (“About Cystic Fibrosis,” n.d.). That is a very large population so as a nurse it is beneficial to know what this disease is and how and why it
Cystic Fibrosis (CF) is the most common fatal genetic disease in the United States today. CF is an autosomal recessive disease that occurs approximately one out of 3,300 live births (Cystic Fibrosis Foundation, 1998). Autosomal means that the gene for CF is not carried on the sex chromosomes and males and females are both afflicted by this disease. Recessive inheritance is when both parents "carry" the abnormal gene in their DNA but they themselves do not show evidence of the disease. The mother and father have one normal gene and one abnormal gene and don't show signs of disease because the normal gene dominates the abnormal gene. To have CF, a child must inherit two abnormal genes, one from each parent. Remember that chromosomes are made up of DNA or deoxyribonucleic acid. DNA is made up of genes, and genes are made up of building blocks called base pairs. The specific gene responsible for CF was identified in 1989 on human chromosome 7 (Pseudomonas Genome Project, 1998). A mutation, or change in the genetic material, resulting in a substitution or loss of one of the base pairs causes the CF gene to be abnormal (Cystic Fibrosis Foundation, 1995).
Cystic fibrosis (CF) is a disease that is caused by a defective gene that is inherited from both parents. The defective gene causes a person’s body to release thick sticky mucus which subsequently causes the patient’s airways to be blocked. Cystic fibrosis is a chronic respiratory disease with typical symptoms being digestion, wheezing, lung infection, stuffy nose, and a persistent cough.
1. One couple in the UK who had a child that died from cystic fibrosis was able to screen their new fetus' genes so that their child would be born healthy (Begley).