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Identification of fragile sites is a way to investigate the genetic abnormalities that are the hallmark of cancer and play an important role in carcinogenesis. Manifestation of nonrandom breakage at a chromosome band is an essential criterion for determination of the fragility of the band. In this article, a new detection procedure is proposed. This new procedure takes the relationship of one site with the others into consideration and can be applied to tests of the randomness of breakpoints under either the proportional probability model (PPM) or the equiprobability model (EPM). The procedure can form a grouping structure that classifies all sites into several clusters. It is applied to identification of fragile sites for a real data set for Chinese patients with colorectal carcinoma for illustration of the proposed method.

Schizophrenia is a common complex mental disorder. The lifetime prevalence of this disease is about 1% across different populations. The etiology is still unknown despite decades of intensive study. This report is aimed at studying the relationship between chromosomal fragile sites and the etiology of schizophrenia. Lymphocytes of 72 schizophrenic patients and 66 healthy controls were cultured in M medium, which is deficient in folic acid, and in medium RPMI 1640 with distamycin A. G-banding was carried out on 100 metaphases of each individual. Fragile sites were characterized as specific chromosomal bands that exhibit nonrandom gaps or breaks. Culture in M medium resulted in significant differences in the total number of chromosomal lesions and the total number of cells with chromosomal lesions between patients and controls (P<0.001), while no difference was noted after exposure to distamycin A. In the case of M medium, 17 bands in both patients and controls were recognized as expressing fragile sites nonrandomly using a statistical method based on the relationship of the binomial and F distributions. Further analysis using Fisher's exact test revealed a significant excess of expression of a rare fragile site at 2q11.2 among patients compared with controls (P<0.05). In the case of distamycin A induction, 13 bands were identified as having nonrandom expression of fragile sites using the same statistical method. A significant excess expression of a fragile site at 9q12 was identified among patients compared with controls by applying Fisher's exact test (P<0.001). Thus, our data suggest that chromosomal bands 2q11.2 and 9q12 are interesting regions that may harbor important genes associated with schizophrenia.

Fragile sites are chromosome bands that do not manifest a presumed breakage pattern. Identification of fragile sites is a way to investigate the mechanism of carcinogenesis because the fragility at a specific chromosome position may be the causation of an associated cancer. A problem in the identification of fragile sites is the high false positive rate arising from simultaneously carrying out a large number of significance tests. To control it, we propose to find a reference study to confirm the identification result of an objective study. We utilize the Bayesian concept for linking two studies. Basically, our method demonstrates a conservative way to take account of the prior information of a binomial parameter. The derived estimate of breakage probability can be interpreted as a resampling weighted sample-pooling method. It is applied to confirm the identification of fragile sites for a data set of neuroblastoma patients.

Testing the nonrandomness of breakage at a chromosome band is an essential step fo identifying a fragile site. In this paper, we propose a method derived by using the relationship between the binomial and F distributions for testing nonrandomness. The method is simple in calculation. It was applied to the detection of fragile sites for Chinese patients with colorectal carcinoma.