Using graph theory to describe and model chromosome aberrations.
A comprehensive description of chromosome aberrations is introduced that is suitable for all cytogenetic protocols (e.g. solid staining, banding, FISH, mFISH, SKY, bar coding) and for mathematical analyses. "Aberration multigraphs" systematically characterize and interrelate three basic aberration elements: (1) the initial configuration of chromosome breaks; (2) the exchange process, whose cycle structure helps to describe aberration complexity; and (3) the final configuration of rearranged chromosomes, which determines the observed pattern but may contain cryptic misrejoinings in addition. New aberration classification methods and a far-reaching generalization of mPAINT descriptors, applicable to any protocol, emerge. The difficult problem of trying to infer actual exchange processes from cytogenetically observed final patterns is analyzed using computer algorithms, adaptations of known theorems on cubic graphs, and some new graph-theoretical constructs. Results include the following: (1) For a painting protocol, unambiguously inferring the occurrence of a high-order cycle requires a corresponding number of different colors; (2) cycle structure can be computed by a simple trick directly from mPAINT descriptors if the initial configuration has no more than one break per homologue pair; and (3) higher-order cycles are more frequent than the obligate cycle structure specifies. Aberration multigraphs are a powerful new way to describe, classify and quantitatively analyze radiation-induced chromosome aberrations. They pinpoint (but do not eliminate) the problem that, with present cytogenetic techniques, one observed pattern corresponds to many possible initial configurations and exchange processes.
Sachs
Rainer K
RK
Department of Mathematics, University of California, Berkeley, California 94720, USA. sachs@math.berkeley.edu
Arsuaga
Javier
J
Vázquez
Mariel
M
Hlatky
Lynn
L
Hahnfeldt
Philip
P
D000465:Algorithms; D002869:Chromosome Aberrations / Q000145:classification* / Q000528:radiation effects; D019457:Chromosome Breakage; D003116:Color; D004249:DNA Damage / Q000528:radiation effects; D017404:In Situ Hybridization, Fluorescence; D008433:Mathematics; D008962:Models, Theoretical; D011336:Probability; D016615:Telomere; D009626:Terminology as Topic