I am playing here a counsellor, for a 1 year old, who has CFTR, F508, N1303K, I have to advise the family, give them introduction of the disease and does it have a treatment.

1. A brief introduction to the disease including the molecular basis of the disease (the membrane protein damage that causes the disease), the size of the gene and the protein, the number of mutations that exist, what class mutation is the one that you are researching and what does it mean?

2. The basic genetics of the disease (including the genetics describing how each parent must carry one CFTR allele in order for a child to have the disease. How many people get the disease? How is it transmitted?

3. A review of the allele combinations that the child might have; you will be assigned a main allele to research in an online database, and will research in the database the three possible combinations of that allele. You will include an explanation of the potential health impact of that allele you have been assigned on the child’s health (for example, impact on the lungs, pancreas, and potential for Pseudomonas infections.

4. The last section should be about possible treatments. Are there new drugs (modulators) that can potentially help to deal with the particular version of CF that the child has? Or are only traditional treatment methods possible? What would those methods be? The database search will give you some information about whether The best place to find information about the drugs is on the Vertex website (link is on the database search page directions).

5. The entire paper should be no longer than 4 double-spaced pages with standard 1-inch margins and a standard font no smaller than 11 points.

Cystic FibrosisProject(100 points)This project is going to be a reportwhere you will beacting as a genetic counselor to the parents of a one-year-old child who has been diagnosed with Cystic Fibrosis. You will be presenting information about a particular variant (mutation) or pair of variants that cause Cystic Fibrosis. You will investigatea variant that you will be assigned, both on its own with an unknown variant on the other chromosome, or with a known common CF variant. There are a variety of web sites that have specific information about cystic fibrosis as a disease and descriptions of the etiology of the disease. The most common websites with reliable information include the following:www.vrtx.comwww.vertextreatments.comhttps://hopkinscf.org/www.cfsource.comhttps://investors.vrtx.com/news-releases/news-release-details/fda-approves-symdekor-tezacaftorivacaftor-and-ivacaftor-treatYou should read through each of these web sites and become familiar with the information contained in each one. Information in them willhelpform the basis of some of the background information for your report. You already know most of the basic information so these sites should help review what you know or add additional information to what you already know.We have reviewedin this coursehow there aresixclasses of variants to which the most common CF variants can be assigned, classes I through VI (Note: there are a few websites that will show 5 different CF mutation classes; these have older information and are missing the 6thvariant description). Information on the manner in which variants in each of these classes causes damage to the CFTR protein can be found at the following websites:https://hopkinscf.org/knowledge/cftr/#section5https://www.cff.org/What-is-CF/Genetics/Types-of-CFTR-Mutations/This website shows only 5 classes of mutations, but the graphic presented is very helpful for understanding the mutation types. The first 5 classes of mutations are the same in each case; the 6thclass is a newer variant that is not described everywhere. Investigating your VariantNow that you have investigatedsome basic information about Cystic Fibrosis, the remainder of the project will present information that is specific to the variant that youareinvestigating. What variant class does your specific variant belong to?Use the previous information you have researched to determine which class your variant belongs to. You should describe the specificmolecular problem with your variant in yourreport.

2Now, go to the website at https://cftr2.org/The entry page to this website will require you to read through and answer some questions in order to get to theactualdatabase site where you can investigate your mutation. Once you get to the main page, there are threeshort videosyou can watch in order to understand the websiteand how it works. Once you have done that, you can enter data in the entry points at the top left of the page (https://cftr2.org/welcome); there are two entry points; the first says Enter first variantand the second says Second variant (optional).The goal is to research three possible combinations:1.Your assigned variant alone; since a person must have two of the genes for cystic fibrosis in order to have the disease, this search will give you information about a situation where a person has cystic fibrosis, but only one of the variants has been identified and the second is unknown. 2.Your assigned variant in both positions (this means thatthe same varianthas been determined to bepresenton both chromosomes)3.Yourassignedvariant in combination with variant F508delin the second position. Each of thesecombinationswill need to be run separately in the database and different information may be examined for each combination. You should report on each of these situations in your report. Each time you run a combination, you will be given results that you should include in your report including 1)Summary Information2)Lung Function3)% with Pancreatic Insufficiency4)Pseudomonas Infection rateCF Variant Information: As you write your report, you should includethe following:1)general background about your specific CF mutationand the class it falls into2)the information you have researched about your specific variant and the implications of the different allele combinations that you researched. 3)What class does your variant fall into? What is the problem that puts this variant into this class? What are the most common clinical manifestations for this variant?4)What percentage of the population with CF carry this variant?5)Is it possible to screen people for the presence of this variant? 6)What treatments may be available for treatment of this patient? Include traditional types of treatments and any newer CFTR modulator treatments and how they work with this variant. The following web sites contain information about testing that can be done to identify the CFTR variants in humans.

3https://www.acog.org/Patients/FAQs/Cystic-Fibrosis-Prenatal-Screening-and-Diagnosis#amhttps://ltd.aruplab.com/Tests/Pdf/182https://www.labcorp.com/test-menu/23686/cystic-fibrosis-cf-profile-32-mutations-fetal-analysisPossible TreatmentsThere are many old style standard therapies to treat CF, and there are the newer CFTR Modulator treatments. Which of these treatments might be useful for patients with your gene variant?As you do your database search, there will usually be some information thatcomes up about whether any of the newer modulator treatments is possible. There are other web sites where you can find specific information if you google the specific name of one of the new modulator treatments. Otherwise you should look into some of the older, standard treatmentsfor the disease. https://www.vertextreatments.com/https://www.cff.org/Life-With-CF/Treatments-and-Therapies/Medications/CFTR-Modulator-Therapies/https://investors.vrtx.com/news-releases/news-release-details/fda-approves-symdekor-tezacaftorivacaftor-and-ivacaftor-treatCystic Fibrosis Genetic Variants1.G542X2.W1282X3.R553X4.N1303K5.I507del6.G551D7.S549N8.R117H9.R347P10.D1152H11.A455E12.2789 + 5G -A

Save the paper as a Word or PDF file to submit.

There are two documents that are included in this project module.

1. The first document has information that will lead you to high quality web sites that will tell you more about cystic fibrosis and help you answer the questions that need to be covered in your paper. It will also walk you through the steps to get to the database that has the information about the mutation that you will be assigned. Look at all of the directions in that document along with the information found here in order to have a complete picture of the project.

2. The second document has a table that will show you which mutation you have been assigned. The list of mutations is in the far left column; you will find your name in one of the rows to the right of one of the mutations. You may NOT switch you assignment with other students in the class. The specific mutation you are researching should be included in the title of your project.

The completed project is worth up to 100 points and a grading rubric will be posted in the next couple of days. The completed project is due no later than July 30th at 11:59 PM.