The patient with bilateral retinoblastoma is missing

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fragment. The patient with bilateral retinoblastoma is missing three fragments entirely and the remaining fragment is present at only half the normal inten- sity. This pattern indicates that the one good Rb gene has been entirely deleted, leaving only the 6.2-kb fragment from the original inherited deletion. C. These results are exactly what is expected from the hypothesis that retinoblastoma is due to the loss of both copies of the Rb gene. Many cases of retinoblastoma have now been examined, and they all show loss or alter- ation of the Rb gene. Thus, retinoblastoma develops in the absence of func- tional Rb.
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References: Fung Y-KT, Murphree AL, T’Ang A, Qian J, Hinrichs SH & Bene- dict WF (1987) Structural evidence for the authenticity of the human retinoblastoma gene. Science 236, 1657–1661. Knudson AG (1971) Mutation and cancer: statistical study of retinoblas- toma. Proc. Natl Acad. Sci. U.S.A. 68, 820–823. 20–44 A. Most of the 463,248 sequence changes that remained after the reading errors were removed have nothing to do with cancer. The authors of this study applied six additional filters to eliminate sequence changes that are unlikely to contribute to the functional differences between the normal cells and the tumor cells. See if your suggestions are included in this list. 1. Filter out changes that do not alter the encoded amino acid sequence; for example, mutations to synonymous codons. (259,957 changes were eliminated by this criterion.) 2. Filter out changes that are also present in the DNA from the two normal individuals that were included in the analysis. (163,006 changes were eliminated by this criterion.) 3. Filter out changes that correspond to known sequence polymorphisms in the human population. (11,004 changes were eliminated by this crite- rion.) 4. Filter out changes that cannot be confirmed upon reamplifying and rese- quencing the sample. (Of the 29,281 sequence differences that remained after applying the above filters, 9295 were not confirmed and therefore eliminated.) 5. Filter out changes that are also present in normal tissue from the same individual that had the tumor. (18,414 of the 19,986 sequence differences that remained after applying filter 4 were eliminated were eliminated by this criterion.) 6. Filter out changes in sequences that have closely related sequences else- where in the genome. There can be problems deciding which genomic location is the true source of the sequence read. (265 of the remaining 1572 sequence differences were eliminated by this criterion, leaving 1307 potential cancer-relevant mutations.) B. Deciding which of these 1307 mutations are likely to contribute to the can- cers is not an easy task. One approach is to look for mutant genes that are found in multiple breast tumors or in multiple colorectal tumors. The underlying assumption is that similar cancers should have similar sets of causative mutations. The authors used this sort of analysis to identify roughly 12 cancer-related mutations in breast tumors, and about 9 in col- orectal tumors. (The rest of the mutations are likely to be passenger muta- tions.) Because only about half the genes in the genome were analyzed
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