MINIMUM SAMPLE SIZES FOR IDENTIFYING CHROMOSOMAL FRAGILE SITES FROM INDIVIDUALS - MONTE-CARLO ESTIMATION

A Monte Carlo simulation procedure was used to estimate the exact leve l of the standardized X-2 test statistic (X-s(2)) for randomness in th e FSM methodology for the identification of fragile sites from chromos omal breakage data for single individuals. A random-number generator w as used to simulate 10000 chromosomal breakage data sets, each corresp onding to the null hypothesis of no fragile sites for numbers of chrom osomal breaks (n) from 1 to 2000 and at three levels of chromosomal ba nd resolution (k). The reliability of the test was assessed by compari sons of the empirical and nominal alpha levels for each of the corresp onding values of n and k. These analyses indicate that the sparse and discrete nature of chromosomal breakage data results in large and unpr edictable discrepancies between the empirical and nominal alpha levels when fragile site identifications are based on small numbers of break s (n < 0.5 k). With n greater than or equal to 0.5 k, the distribution of X-s(2) appears to be stable and non-significant differences in the empirical and nominal a levels are generally obtained. These results are inherent to the nature of the data and are, therefore, relevant to any statistical model for the identification of fragile sites from ch romosomal breakage data. For FSM identification of fragile sites at al pha = 0.05, we suggest that n greater than or equal to 0.5 k is the mi nimum reliable number of mapped chromosomal breaks per individual.