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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Identification and characterization of human DFNA5L, mouse Dfna5l, and rat Dfna5l genes in silico.

An evolutionary recombination hotspot around the GSDML-GSDM locus at human chromosome 17q21 is closely linked to an oncogenomic recombination hotspot around the PPP1R1B-STARD3-TCAP-PNMT-PERLD1 (MGC9753)-ERBB2-C17orf37 (MGC14832)-GRB7 locus at human chromosome 17q12. Here, we identified DFNA5L (GSDMDC1) gene related to GSDM and GSDML genes by using bioinformatics. Human DFNA5L gene at chromosome 8q24.3 was linked to ZC3HDC3, PP3856, EEF1D, and TIGD5 genes. NM_024736.4 (AK127941.1), AK022212.1, BC008904.2, and BC069000.1 cDNAs were derived from human DFNA5L gene. BC008904.2 was the representative human DFNA5L cDNA, while NM_024736.4 was an aberrant human DFNA5L cDNA with frame shifts due to the retention of introns 1, 3, 4, 5 and 8. Human DFNA5L mRNA was expressed in placenta, pancreatic cancer, prostate cancer, melanoma, salivary gland tumor, Jarkat T cells, and Ramos B cells. Complete coding sequence of rat Dfna5l cDNA was determined by assembling 11 exons of rat Dfna5l gene within AC120830.4 genome sequence, and that of mouse Dfna5l cDNA was derived from 1810036L03 (NM_026960.1). Exon-intron boundaries were conserved among human DFNA5L and rodent Dfna5l genes. Human DFNA5L (484 aa) showed 59.5% total-amino-acid identity with rat Dfna5l (488 aa), and 58.7% total-amino-acid identity with mouse Dfna5l (487 aa). DFNA5L orthologs were DNFA5 (GSDM) domain containing DFNA5 DC or GSDMDC proteins with Coiled-coil and Leucine zipper domains. Human DFNA5L, GSDM, GSDML, MLZE, DFNA5 and their mammalian orthologs were found to constitute the DFNA5 DC ( GSDMDC) family. Because DFNA5 and MLZE are cancer-associated genes, DFNA5L, GSDM, and GSDML are predicted cancer associated genes.[1]

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