(A) Restriction map of p16. Open boxes denote the three coding exons, shaded box stands for the 3′ untranslated region (UTR) of p16. Exon 1 resides in a 4.3-kb EcoRI restriction fragment. Methylation-sensitive, rare base-cutting resriction enzymes include 3 Sma I (Sm), 2 SacII (Sa), and 2 Eag I (E) sites. The location of PCR-generated probe used for Southern analysis is shown at the top. Below are the expected fragment sizes recognized by this probe when digested with the restriction enzymes shown in the normally unmethylated status. (Adapted and reprinted with permission.25 ) (B) Restriction map of p15. The probe used for Southern analysis is shown at the top. Exons 1 and 2 are depicted, with noncoding regions shaded. Methylation-sensitive restriction enzyme sites and HindIII sites are shown in the region including exon 1. The predicted sizes of restriction fragments used to analyze the methylation status of p15 are shown at the bottom. (Adapted and reprinted with permission.17 )