The human homolog of the Moloney leukemia virus integration 2 locus (MLV12) maps to band p14 of chromosome 5.

The Moloney leukemia virus integration 2 (MLV12) locus represents a common region for proviral integration and a putative oncogene involved in the induction of thymic lymphomas in rodents. The human homolog of the MLV12 locus has been cloned and studies have been initiated to determine its possible role in the induction and progression of human neoplasms. In this study we used a panel of human X rodent somatic cell hybrids and in situ hybridization to metaphase chromosomes to map MLV12 to the short arm of the human chromosome 5, band p14.

Insertion of an Alu SINE in the human homologue of the Mlvi-2 locus.

Fifty-nine human DNA samples derived from either normal tissues or hematopoietic neoplasias were examined for rearrangements in the Mlvi-2 locus, a putative oncogene. The rearranged Mlvi-2 sequences in one of them, a B cell lymphoma, were shown to result from the insertion of an approximately 300 bp DNA fragment that hybridized to a human Alu probe. DNA sequence analysis of both the rearranged and the nonrearranged allele around the site of the insertion revealed the following: a) the insert was 88.4% homologous to the consensus sequence of the Alu family of repeats and 75% homologous to the Alu related sequence in the human 7SL RNA; b) similar to other sequenced SINES, a poly(d.A) tract was present at the 3' end of this element; c) an 8 bp direct repeat was present at both ends of the inserted element; d) this repeat was present as a single copy in the unrearranged allele. We conclude from these findings that: Alu sequences can transpose and that the direct repeats flanking certain Alu SINES may be generated by the duplication of single copy cellular sequences at the site of the insertion. Furthermore the recent nature of the Alu insertion in the Mlvi-2 locus coupled to the low degree of homology of the inserted Alu to the Alu related sequence in the 7SL RNA suggest that this event did not occur via reverse transcription and reintegration of the 7SL RNA.

Insertion of long interspersed repeated elements at the Igh (immunoglobulin heavy chain) and Mlvi-2 (Moloney leukemia virus integration 2) loci of rats.

Restriction enzyme analysis of normal DNA derived from individual rats of the National Institutes of Health outbred Osborn-Mendel colony revealed that two independent single-copy loci, the Igh (immunoglobulin heavy chain) locus and the Mlvi-2 (Moloney leukemia virus integration 2) locus, a putative oncogene, are polymorphic (i.e., exhibit allelic variation). The polymorphism at both loci was due to the presence or absence of a long interspersed repeated DNA element (LINE). The LINE insertion in the Igh locus occurred in the joining (J) region, which is involved in the physiological rearrangement of this locus. The LINE insertion in the Mlvi-2 locus has occurred approximately 6 kilobases from the region of provirus integration in Moloney murine leukemia virus-induced rat thymomas. The two inserts are colinear with each other and with other randomly selected cloned copies of the rat LINE family, the general characteristics of which we also present. LINE insertion in the Mlvi-2 locus was observed in several rat strains, established from independent rat colonies, suggesting that LINE-containing Mlvi-2 alleles may be widespread in the rat population. LINE insertion in the Igh locus was observed in 1 of 27 rats. The detection of a LINE-related polymorphism at two nonselected loci indicates that LINEs are transposable. The presence or absence of these long (greater than 5 kilobases), highly transcribed elements at single-copy loci could have profound effects on gene activity. Furthermore, LINE-containing single-copy loci could be affected by homologous interaction between the resident LINE and any of the other 50,000 or so copies of these elements in the rat genome.