Cytogenetic location: 1q Genomic coordinates (GRCh38): 1:123,400,001-248,956,422
LRE1 (LE retrotransposable element 1; 151626), a gene located on chromosome 22, contains 2 open reading frames (ORFs), the first encoding a predicted 40-kD protein and the second encoding a reverse transcriptase activity. This gene was found by the Kazazian group to be the cause of hemophilia A when inserted into the factor VIII gene, as detailed in entry 306700. Insertions of the L1 sequence into the dystrophin gene (300377) resulting in Duchenne muscular dystrophy (310200) were reported by Narita et al. (1993). Holmes et al. (1994), of the Kazazian group, reported the identification of another L1 insertion into the DMD gene and identified and characterized its precursor based on the presence of a single-copy unique sequence component (USC) flanking both the insertion and the precursor. The precursor locus, LRE2, had 1 allele derived from the patient that matched the insertion sequence exactly. LRE2 has a perfect 13- to 15-bp target site duplication, 2 ORFs, and an unusual 21-bp truncation of the 5-prime end. It differed from LRE1 by approximately 0.7%. Holmes et al. (1994) mapped the LRE2 locus to chromosome 1 by analysis of genomic DNA from human/hamster somatic cell hybrids where a single band was obtained from cells containing human chromosome 1. Using human/mouse somatic cell hybrids containing portions of human chromosome 1 and PCR primers, they regionalized the gene to 1q. They demonstrated that an L1 element at the LRE2 locus is present on approximately 66% of human chromosomes and that the element is absent in chimpanzee and gorilla genomes.
Holmes, S. E., Dombroski, B. A., Krebs, C. M., Boehm, C. D., Kazazian, H. H., Jr. A new retrotransposable human L1 element from the LRE2 locus on chromosome 1q produces a chimaeric insertion. Nature Genet. 7: 143-149, 1994. [PubMed: 7920631] [Full Text: https://doi.org/10.1038/ng0694-143]
Narita, N., Nishio, H., Kitoh, Y., Ishikawa, Y., Ishikawa, Y., Minami, R., Nakamura, H., Matsuo, M. Insertion of a 5-prime truncated L1 element into the 3-prime end of exon 44 of the dystrophin gene resulted in skipping of the exon during splicing in a case of Duchenne muscular dystrophy. J. Clin. Invest. 91: 1862-1867, 1993. [PubMed: 8387534] [Full Text: https://doi.org/10.1172/JCI116402]