Isochores merit the prefix 'iso'

The isochore concept in the human genome sequence was challenged in an analysis by the International Human Genome Sequencing Consortium (IHGSC). We argue here that a statement in the IHGSC's analysis concerning the existence of isochores is misleading, because the homogeneity was not examined at a large enough length scale and consequently an inappropriate statistical test was applied. A test of the existence of isochores should be equivalent to a test of homogeneity or equality of windowed GC%. The statistical test applied in the IHGSC's analysis, the binomial test, is a test of whether individual bases are independent and identically-distributed (iid). For testing the existence of isochores, or homogeneity in windowed GC%, we propose to use another statistical test: the analysis of variance (ANOVA). It can be shown that DNA sequences that are rejected by the binomial test may not be rejected by the ANOVA test. (C) 2002 Elsevier Science Ltd. All rights reserved.