Identifying chromosomal fragile sites from individuals: a multinomial statistical model.
The inability to identify fragile sites from data for single individuals remains the major obstacle to determining whether these chromosomal loci are predisposed to cancer-causing and evolutionary rearrangements. We describe a novel statistical model that is amenable to data from single individuals and that establishes site-specific chromosomal breakage as nonrandom with respect to the distribution of total breakage. Our method tests incrementally smaller subsets of the data for homogeneity under a multinomial model that assigns equal probabilities to a maximal set of nonfragile sites and unrestricted probabilities to the remaining fragile sites with significantly higher numbers of breaks. We show how standardized Pearson's chi-square (X2) and likelihood-ratio (G2) statistics can be appropriately used to measure goodness-of-fit for sparse contingency (individual-based) data in this model. A sample application of this approach indicates extensive variation in fragile sites among individuals and marked differences in fragile-site inferences from pooled as opposed to per-individual data.
Böhm
U
U
Department of Statistics, Texas A & M University, College Station 77843.
Dahm
P F
PF
McAllister
B F
BF
Greenbaum
I F
IF
D000818:Animals; D016009:Chi-Square Distribution; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D015233:Models, Statistical; D010542:Peromyscus