alexa Duplication of a genomic region containing the Cdc2L1-2 and MMP21-22 genes on human chromosome 1p36.3 and their linkage to D1Z2.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Gururajan R, Lahti JM, Grenet J, Easton J, Gruber I,

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Abstract Cdc2L1 and Cdc2L2 span approximately 140 kb on human chromosome 1p36.3. The products of the Cdc2L genes encode almost identical protein kinases, the PITSLRE kinases, which have functions that may be relevant to the regulation of transcription/splicing and apoptotic signaling. These genes are deleted/translocated in neuroblastomas with MYCN gene amplification, a subset of malignant melanomas, and in a newly delineated deletion syndrome. Here we report that the p36.3 region of human chromosome 1 consists of two identical genomic regions, each of which contain a Cdc2L gene linked to a metalloprotease (MMP) gene in a tail-to-tail configuration. This duplicated genomic region is also linked tightly to D1Z2, a genetic marker containing a highly polymorphic VNTR (variable number tandem repeat) consisting of an unusual 40-bp reiterated sequence. Thus, these genes and the polymorphic marker D1Z2 are organized as follows: telomere-D1Z2-5'-MMP22-3'-3'-Cdc2L2-5'-5'-Cdc2L1 -3'- 3'-MMP21-5'-centromere. Remarkably, the introns and exons of Cdc2L1 and Cdc2L2, as well as their flanking regions, are essentially identical. A total of 15 amino acid differences, 12 nonconservative and 3 conservative, can be found in the 773-786 amino acids specified by the various products of the Cdc2L genes. Two separate promoter/5' untranslated (UT) regions, CpG1 and CpG2, are identical to a reported previously methylated genomic CpG sequence and are used to express >20 different Cdc2L transcripts from the two genes. The expression of CpG2 transcripts from Cdc2L1 and Cdc2L2 is tissue/cell-line specific. CpG1 transcripts are expressed ubiquitously from both genes, with perhaps some bias towards the expression of CpG1 Cdc2L1 mRNAs in certain hematopoietic cells.
This article was published in Genome Res and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

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