Friday, October 24, 2014
Let's Look at CF and make more connections to membranes & transport.
This week, lets find out more about how defective chloride channels lead to a condition known as cystic fibrosis. Please post what you can find out. Please post at least one fact/puzzle piece each day (Monday, Tuesday & Wednesday) this week so that by Thursday, a complete picture will be formed. Provide links to your sources if they are online, otherwise tell us where you found the information. Thank you.
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Cystic Fibrosis is caused by a mutation of the cystic fibrosis transmembrane conductance regulator gene on chromosome 7 that effects the protein that helps salts(NaCl) move in and out of the cell.
ReplyDeleteSource:http://learn.genetics.utah.edu/content/disorders/singlegene/cf/
An individual must inherit two defective cystic fibrosis genes (one from each parent) to get the disease. Each time the two parents who are carriers of the disease conceive, there is a 25% chance they will pass the disease onto their children, a 50% chance the child will be the carrier of the mutated gene, and 25% chance the child will not carry the gene.
ReplyDeletehttp://www.who.int/genomics/public/geneticdiseases/en/index2.html#CF
Cystic fibrosis is characterized by damage to body organs and body systems due to the build up of thick mucus. CF in many cases will cause the most extensive damage to the respiratory and digestive systems. People with CF produce mucus that is more thick and sticky than the mucus of a person without CF. The thick sticky mucus can cause airways in the lungs to clog causing breathing restrictions and also bacterial infections in the lungs. Symptoms of CF include chronic coughing, wheezing, and inflammation of the respiratory system. In the most severe cases buildup of mucus in the respiratory system can cause permanent lung damage usually due to the formation of scar tissue.
ReplyDeleteThis a REALLY good source if anyone wants to use it for their post!
http://ghr.nlm.nih.gov/condition/cystic-fibrosis
Approximately 30,000 people in the United States, and 70,000 worldwide, have Cystic Fibrosis. About 1,000 new cases are diagnosed each year and 75% of people with CF are diagnosed before the age of 2.
ReplyDeleteSource: http://www.cff.org/AboutCF/
There is no cure for Cystic fibrosis currently however there are multiple treatment options. Patients with CF can go to physical therapy for their lungs to loosen mucus and make it easier to cough up. Patients can also receive antibiotics to prevent lung infections and can take mucus thinners to improve lung function.
ReplyDeleteSource: http://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/basics/treatment/con-20013731
The CTFR protein is used as a channel for the movement of chloride ions in and out of the cells. A mutation in this gene causes changes in the amino acid sequence in the primary structure of the CTFR protein. This then leads to changes in the secondary, and tertiary structures. The incorrect folding of this protein causes it to not function correctly. The protein can be mutated to be unfit to sit in the membrane of the cell or it can also not be able to open and close the channel properly. This makes the cell unable to properly transport chloride ions. This is primarily in the epithelial cells. This unbalanced chloride ion content makes the mucous produced by the cells very sticky.
ReplyDeleteGreat source (below) and thank you for describing the channel protein in more detail. Hopefully your peers can add more specific examples to the excellent framework you have provided.
Deleteoops i forgot my source
ReplyDeletehttp://www.nchpeg.org/nutrition/index.php?option=com_content&view=article&id=462&Itemid=564&limitstart=4
The liver, biliary tract and the pancreas are also affected by cystic fibrosis. Blockage of the pancreatic ducts can reduce the secretion of digestive enzymes which results in a disruption of the breakdown and absorption of food in the intestine.
ReplyDeleteSource: http://www.news-medical.net/health/Cystic-Fibrosis-Facts.aspx
The gene mutations for Cystic Fibrosis are found on chromosome 7. There are multiple mutations that can cause cystic fibrosis and one is the F508del mutation. this mutation is one of many that cause, as Ryan said, pancreatic insufficiency when paired with another CF causing mutation. It is the most common CF causing mutation but is one of hundreds.
ReplyDeleteSource: http://www.cftr2.org/mutation.php?view=general&mutation_id=1
CF is caused by mutations found in the CFTR genes. The CFTR gene generates the genetic coding instructions for transport protein channels that allow negatively charged ions to flow in and out of the cell. Since chloride is a component of sodium chloride, a common salt found in sweat, it has important functions in cells. For example, the transport of chloride ions helps control the movement of water in the tissues of the, which is necessary for the production of "thin, freely flowing mucus.” The mutation in the gene prohibits the transport of chloride into and out of the cells in the body, causing mucus to become think and sticky. This is the most common characteristic of the CF disease.
ReplyDeletehttp://ghr.nlm.nih.gov/condition/cystic-fibrosis
During adolescence, people who are insulin deficient can develop a form of diabetes known as cystic fibrosis-related diabetes mellitus or (CFRDM).
ReplyDeletehttp://ghr.nlm.nih.gov/condition/cystic-fibrosis
People with cystic fibrosis have more than 1,000 mutations in the CFTR. These mutations change single protein building blocks (amino acids) in the CFTR protein or delete a small amount of DNA from the CTFR gene. The most common mutation is called delta F508 and is a deletion of one amino acid. An abnormal channel results from this and breaks down shortly after it is made, so it never reaches the cell membrane to transport chloride ions. Mutations in the CFTR gene also alter the production, structure, or stability of the chloride channel.
ReplyDeletehttp://ghr.nlm.nih.gov/gene/CFTR
The symptoms of cystic fibrosis can vary, and include: frequent lung infections, shortness of breath, very salty skin, and poor growth/slow weight gain. The respiratory related symptoms are a result of the clogging of the lungs and the slow growth is a result of the inability of the body to break down food and absorb important nutrients.
ReplyDeletesource: http://www.cff.org/AboutCF/
If the CFTR gene is mutated it can alter the protein structure and function. Some changes that can occur are a shortened protein,the protein never reaches the cell membrane, the protein channel can not be regulated properly, and the function of the protein can be reduced due to incorrect splicing of the gene.
ReplyDeleteSource:http://www.nchpeg.org/nutrition/index.php?option=com_content&view=article&id=462&Itemid=564&limitstart=4
The CFTR gene contains 27 exon segments. Each segment is spliced together to form a complete mRNA message. The message is then translated into a chain of amino acids that forms the protein responsible for the CFTR gene.If the protein folds up into the correct 3 dimensional shape then it will be able to position itself correctly in the cell membrane and function as an ion channel. If it is not the proper shape then the ion channel will not function to allow chloride ions in and out of the cell. This causes CF and the build of thick sticky mucus. Again water follows the chloride ions, so without them water is not able to become part of the mucus when it is produced.
ReplyDeletehttp://www.nchpeg.org/nutrition/index.php?option=com_content&view=article&id=462&Itemid=564&limitstart=4
The CTFR acts as a protein channel that transports chloride ions. This is transport involves the input of ATP, so it is considered active transport. This protein also acts as a regulator for other protein channels. Some of the mutations have been found to affect the the way ATP binds to the protein, so it cannot function to transport chloride ions.
ReplyDeletehttp://atlasgeneticsoncology.org/Educ/CistFibID30032ES.html http://users.ox.ac.uk/~genemed/cysticfibrosis/function.html
The CTFR’s protein’s role allows chloride ions to exit the mucus producing cells. When the chloride ions leave these cells, water flows and this thins the mucus. The CTFR protein helps keep the mucus from becoming thick and slow. It allows the mucus to be moved steadily along passageways, and aids in cleansing. However, in cystic fibrosis, the protein doesn’t allow chloride ions out of the mucus-producing cells. This makes less chloride and water leave the cells, and mucus becomes thick and sticky.
ReplyDeletehttp://medical-dictionary.thefreedictionary.com/Cystic+Fibrosis
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ReplyDeleteScientists have discovered and described over one thousand mutations that affect the CFTR gene. Each mutation effects the gene in a different way. The most common CFTR mutation consists of a deletion of three DNA nucleotides. The deletion causes a single phenylalanine amino acid to be removed from the CFTR gene. The deletion of an the amino acid phenylalanine occurs at position 508 of the protein sequence of the CFTR gene. This particular mutation is denoted as "ΔF508, and can be found in almost 90% of patients with CF.
ReplyDeleteOther described mutations DIRECTLY from website (not my work)
I Shortened protein W1282X Instead of inserting the amino acid tryptophan (W), the protein sequence is prematurely stopped (indicated by an X). 7
II Protein fails to reach cell membrane ΔF508 A phenylalanine amino acid (F) is deleted 85
III Channel cannot be regulated properly G551D A “missense” mutation: instead of a glycine amino acid (G), aspartate (D) is added
IV Reduced chloride conductance R117H Missense
V Reduced due to incorrect splicing of gene 3120+1G>A Splice-site mutation in gene intron 16
http://www.nchpeg.org/nutrition/index.php?option=com_content&view=article&id=462&Itemid=564&limitstart=4
ReplyDelete