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Ch. 13 Notes: Mutations and Regulation of Gene Expression Gene Mutations Mutation = permanent change in the sequence or number of nucleotides in DNA o if in gametes, passes on from generation to generation o if in somatic cells, passes on from cell to daughter cells Mutagenesis = creation of mutations o May be spontaneous = cellular accidents Ex. Transposons = pieces of DNA that “jump” from one location to another, disrupting gene expression o Replication errors happen but are rare (1 in 1 billion base pairs) May be induced = triggered by environmental effects Mutagens = physical or chemical agents that interact with genetic material to cause mutations o Ex. Radiation (like X-rays) and chemicals (like radon) Point Mutations = mutations that involves a single nucleotide Substitution = changing one nucleotide with a different one o May be: Silent mutation = has no effect on the amino acid sequence codes for same amino acid Missense mutation = codes for and inserts a different amino acid May affect protein structure and function o Ex. Hemoglobin one nucleotide difference between normal and sickle cell hemoglobins (T changed to A Glu changed to Valine) conservative = doesn’t make difference in protein’s tertiary structure nonsense mutation = changes a sense codon to a STOP codon Frameshift Mutations = a deletion or addition of nucleotides may cause a shift in the reading frame of mRNA 1) Deletion = one or more nucleotides are omitted from the sequence 2) Insertion = one or more extra nucleotides are added to the sequence o changes the codon triplets read from that point on Ex. THE RED CAT ATE THE FAT RAT almost always bad All mutations have the potential to have huge impacts on the phenotype, especially if they create nonfunctional proteins Most critical if they are part of a metabolic pathway o Ex. PKU, albinism, and androgen insensitivity CANCER Occurs when a cell escapes from the normal controls on growth and division (the cell cycle) Caused by accumulations of mutations that alter normal gene expression in somatic cells that are random and spontaneous o This is why cancer becomes more common with aging Carcinogens = physical agents such as X-rays and chemical agents that cause cancer by mutating DNA o May activate oncogenes = cancer-causing genes Proto-oncogenes = gene that normally codes for regulatory proteins controlling cell growth, division and adhesion, and that can be transformed by mutation into an oncogene Three types of mutations can convert proto-oncogenes to oncogenes: o Movement of DNA within the genome Often have broken and rejoined pieces of DNA o Gene amplification o Point mutations Changes in tumor-suppressor genes that normally inhibit growth can also promote cancer. Oncogene proteins and faulty tumor-suppressor proteins interfere with normal signaling pathways “Guardian Angel” proteins exist that prevent a cell from passing on mutations due to DNA damage o Ex. suicide genes make products that cause cell death (apoptosis) Multiple mutations underlie the development of cancer Viruses play a role in about 15% of human cancer cases worldwide Genetics also plays a role in many cancers