The table in this problem summarizes some of the data that have been collected on mutations in the BRCA1 tumor-suppressor gene in families with a high incidence of both early-onset breast cancer and ovarian cancer.
Predisposing Mutations in BRCA1
Kindred Codon Nucleotide Coding Effect Frequency in
Change Control
Chromosomes
1901 24 -11 bp Frameshift 0/180
or splice
2082 1313 C→T Gln→Stop 0/170
1910 1756 Extra C Frameshift 0/162
2099 1775 T→G Met→Arg 0/120
2035 NA* ? Loss of NA*
transcript _
Source: (1994). Science 266:66–71. © AAAS.
Note the coding effect of the mutation found in kindred group 2082. This results from a single base-pair substitution. Draw the normal double-stranded DNA sequence for this codon (with the 5' and 3' ends labeled), and show the sequence of events that generated this mutation, assuming that it resulted from an uncorrected mismatch event during DNA replication.
19. Cancer Genetics
Cancer Mutations