always able to promote S phase, and the arrest of normal cells in late G1 does not occur in retinoblastoma cells. As already noted, the germ-line rb mutation is only one event leading to the loss-of-function rb phenotype. The other allele has to be knocked out as well, which can occur through mutation or through deletion of the other allele or through a mitotic abnormality (mitotic crossing-over or mitotic nondisjunction). Of these, deletion and mitotic crossing-over or nondisjunction would lead to the loss of one of the two alleles of the gene, a condition called loss-of-heterozygosity, or LOH for short. There are now many ways to identify loss-of-heterozygosity in tumor cells by comparing their DNA content with their wild-type neighbors, by using molecular polymorphisms such as SNPs, SSLPs, or RFLPs (see Chapter 12). To think about this from the opposite direction, if we were to identify a region of the genome that consistently exhibited LOH in a particular type of tumor, we would be highly suspi-
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This note was uploaded on 01/10/2011 for the course BIOL BIOL taught by Professor Johnson during the Spring '08 term at Aberystwyth University.