Mutations or other aberrations in the expression of genomic stability genes such as those involved in DNA repair or induction of apoptosis can drive
hypermutable phenotypes in tumors.
The researchers surmised that
hypermutable genes could be relevant to disease.
(Exton, PA) has patented dominant-negative alleles of human mismatch repair genes can be used to generate
hypermutable cells and organisms.
Familial colorectal cancer in Ashkenazim due to a
hypermutable tract in APC.
Although one of the
hypermutable populations exhibited an unusually high level of variation for fitness, the other
hypermutable population did not.
Hall proposes that some cells, when stressed by starvation, enter a "
hypermutable" state in which mutations of all sorts abound; but only those cells with the specific mutation that solves the immediate problem (in this case, the inability to synthesize tryptophan) survive.
Resolution of nearly identical genotypes might also be accomplished by using additional VNTRs (8) or
hypermutable loci (9).
(Philadelphia, PA) have patented an approach used to generate
hypermutable plants through the expression of dominant negative alleles of mismatch repair genes in transgenic plants or derived cells.
When a subsequent somatic mutation inactivates the normal, wild-type allele of the same DNA mismatch repair gene, gene instability and a
hypermutable phenotype result, and the multistep process of tumorigenesis is accelerated.
The
hypermutable CG dinucleotide is frequently associated with point mutations of various genes (39).
Hypermutable sites in mitochondrial D-loop sequence data can be detected from the fact that differences between similar (and presumably closely related) sequences tend to occur at sites that are already highly polymorphic and that therefore have a history of high rates of substitution (Wills 1995).
I propose an explanation of these observations in terms of second-order selection of
hypermutable (mutator) alleles based on alterations in DNA repair genes.
