Mapping and molecular characterization of five HMG1-related DNA sequences

Recently, the high mobility group (HMG) proteins have attracted a lot of interest since it was shown that some members of that group can causally be involved in tumorigenesis. One HMG protein gene member is HMG1 for which the number of related DNA sequences has been estimated to be approximately 20-30. Nevertheless, besides the gene for HMG1 only one retropseudogene has been molecularly characterized. It was the aim of this study to map and characterize further sequences related to HMG1. PCR-screening of a PAC library resulted in 25 very strongly positive clones apparently containing HMG1-like cDNA sequences. Of eight clones which were further investigated five were distinguishable from each other based on their chromosome assignment and DNA sequence. Due to their homology to the HMG1 gene the DNA sequences were designated as HMG1L1, HMG1L3, HMG1L4, HMG1L5, and HMG1L6. By FISH experiments they were assigned to 2q32, 2q35, 3p24, 15q22, and 20q13, respectively. Except for one sequence, they did not show mutations leading to a frame shift or a new termination codon. Thus, we cannot exclude that these four HMG1-related DNA sequences represent active genes or can at least be activated e.g. by chromosome rearrangements in tumor cells. So far, the existence of six genes encoding HMG proteins has been described but because of a high frequency of closely related DNA sequences in the human genome it can be assumed that some of them are either pseudogenes or very similar genes.