From Genes to Genetic Diseases DNA Research Paper Ashtyn Brewster (AB10724) Determining How a Disease Gene Is Mutated 2. 2a. Cystic fibrosis is an inherited disease that causes a mucus buildup in the respiratory and digestive systems. The mutated gene that causes cystic fibrosis is called CFTR. CFTR gene’s job is to provide the cell with instructions for making and providing a channel that transports chloride ions in and out of the cell. With the mutation the CFTR gene is unable pass the chloride ions and water through the membrane which causes a build-up of sticky mucus blocking airways. This causes the body to have trouble breathing and may cause a bacterial infection in the lungs. 2b. i. The symptoms and problems of cystic fibrosis include chronic digestive system problems and damage to the respiratory system. ii. The mutated gene that causes cystic fibrosis is the CFTR gene. 3. 4. 4a. The CFTR gene belongs to the family of ABC (ATP-binding cassette transporters) genes. 4b. The CFTR gene is located on chromosome 7q31.2. 4c. The amino acid most commonly mutated to cause cystic fibrosis is F508. 5. 5a. Genes of the ABC family provide instructions for making proteins that transport and carry molecules such as fats, sugars, amino acids and drugs across the cell membrane. 5b. All of the genes in this family are grouped together because they have common structures that bind to ATP. From Genes to Genetic Diseases DNA Research Paper Ashtyn Brewster (AB10724) From DNA to Amino Acids 1. Transcript Mutation 1408G>A 1516A>G 4002A>G 2694T>G 4521G>A rsID rs213950 rs1800091 N/A N/A N/A Codon Sequence Change (DNA) GTG → ATG ATC → GTC CCA → CCG ACT → ACG CAG → CAA Codon Sequence Change (mRNA) GUG → AUG AUC -> GUC CCA -> CCG ACU -> ACG CAG -> CAA Amino Acid Sequence Change Effect Pathogenic or NonPathogenic V [Val] → M [Met] Changes from a neutral, nonpolar amino acid to another neutral, nonpolar amino acid. NonPathogenic L [Lle] -> V [Val] Changes from a neutral nonpolar amino acid to another neutral, nonpolar amino acid. NonPathogenic P [Pro] -> A [ Ala] Changes from a polar, uncharged amino acid to a nonpolar amino acid. NonPathogenic T [Thr] -> T [Thr] Changes from a polar, uncharged amino acid to another uncharged amino acid. NonPathogenic G [Gln] -> G [Gln] Changes from a polar, uncharged amino acid to another NonPathogenic From Genes to Genetic Diseases DNA Research Paper Ashtyn Brewster (AB10724) uncharged amino acid. 1477C>T 1013C>T 1040G>T 1645A>C 1727G>C Rs7710217 Rs77409459 Rs77932196 Rs121908757 Rs1800098 CAG -> TAG ACC -> ATC CGG -> CAC AGT -> CGT GGA -> GCA CAG -> UAG ACC -> AUC CGG -> CAC AGU -> CGU GGA -> GCA G [Gln] -> Stop Ends from a polar, uncharged amino acid. Pathogenic T [Thr] -> L [Lle] Changes from a polar, uncharged Amino Acid to a nonpolar amino acid. Pathogenic A [Arg] -> H [His] Changes from a positively charged Amino acid to another positively charged amino acid. Pathogenic S [Ser] -> A [Arg] Changes from a Polar, uncharged Amino Acid to a positively charged amino acid. Pathogenic G [Gly] -> A [Ala] Changes from a nonpolar amino acid to another nonpolar amino acid. Pathogenic Pathogenic Pathogenic 2780T>C Rs397508435 CTT -> CCT CUU -> CCU L [Leu] -> P [Pro] Changes from a nonpolar amino acid to a polar, uncharged Amino Acid. 3611G>C Rs121908764 TGG -> UGG -> T [Trp] -> Ends from an From Genes to Genetic Diseases DNA Research Paper Ashtyn Brewster (AB10724) 2128A>T 1651G>A 3212A>C Rs75115087 Rs121909013 Rs121909037 TAG UAG Stop AAA -> TAA AAA -> UAA L [Lys] -> Stop Ends from a positively charged amino acid. Pathogenic G [Gly] -> S [Ser] Changes from a nonpolar amino acid to a polar, uncharged amino acid. Pathogenic G [Gln] -> P [Pro] Changes from a polar, uncharged amino acid to another polar, uncharged amino acid. Pathogenic GGT -> AGT CAG -> CCG GGU -> AGU CAG -> CCG aromatic amino acid. b. Point mutations would have a lesser effect on the change of the amino acid sequence. i. All of the non-pathogenic alleles have a point mutation. c. i. *found fasta sequence* ii. The nucleotide would have a frame shift mutation or would stay the same. Testing How the Mutation Matters 3b. I think some of the differences change the number of amino acids brought to the cell, creates codons without complementary anti-codons, and changes the number of mRNA bases that make up the codons. 3c. Non-pathogenic alleles do not disrupt the protein’s function because only one allele is changed. From Genes to Genetic Diseases DNA Research Paper Ashtyn Brewster (AB10724) Vocabulary: Genes - the basic physical unit of heredity DNA - an extremely long macromolecule that is the main component of chromosomes and is the material that transfers genetic characteristics in all life forms, constructed of two nucleotide strands coiled around each other in a ladder-like arrangement with the sidepieces composed of alternating phosphate and deoxyribose units and the rungs composed of the purine and pyrimidine bases adenine, guanine, cytosine, and thymine Mutation - a sudden departure from the parent type in one or more heritable characteristics, caused by a change in a gene or a chromosome. Genetic disease - A disease caused by the absence of a gene or by products of a defective gene. Nucleotides - any of a group of molecules that, when linked together, form the building blocks of DNA or RNA. RNA - ribonucleic acid: any of a class of single-stranded molecules transcribed from DNA in the cell nucleus or in the mitochondrion or chloroplast, containing along the strand a linear sequence of nucleotide bases that is complementary to the DNA strand from which it is transcribed - to make an exact copy of (a document, text, etc.). Transcription – the act of making an exact copy of (a document, text, etc.). Translation - the genetic code carried by mRNA is decoded to produce the specific sequence of amino acids in a polypeptide chain Amino acids - the building blocks from which proteins are constructed. From Genes to Genetic Diseases DNA Research Paper Ashtyn Brewster (AB10724) Codon - a triplet of adjacent nucleotides in the messenger RNA chain that codes for a specific amino acid in the synthesis of a protein molecule. Hydrophilic - having a strong affinity for water. Hydrophobic - having little or no affinity for water. Allele - any of several forms of a gene, usually arising through mutation, that are responsible for hereditary variation. Extra Questions: How does a gene become a protein? DNA creates mRNA to send to the ribosomes that read it, and converts it to three bases that turn into an amino acid. A more complex packaging and Tertiary process occur in the Golgi Apparatus. The enzyme is now ready for use. In a given gene, what kind of DNA mutation would not change the protein that is made? A silent mutation would not change the protein that is made. What makes some amino acids hydrophobic and others hydrophilic? When an amino acid is hydrophobic, the amino acids tend to go to the inside of a protein. When an amino acid is hydrophilic, the amino acids tend to go to the outside of a protein. How common are mutations in the human genome? The mutation frequency is very low considering the human DNA can most likely correct itself. Is it very likely or very unlikely that your DNA carries any mutations? It is very unlikely that your body will carry any mutations. From Genes to Genetic Diseases DNA Research Paper Ashtyn Brewster (AB10724)