Gene structure and expression study of the SEDL gene for Spondyloepiphyseal Dysplasia Tarda

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dc.contributor.authorGecz, J.
dc.contributor.authorHillman, M.
dc.contributor.authorGedeon, A.
dc.contributor.authorCox, T.
dc.contributor.authorBaker, E.
dc.contributor.authorMulley, J.
dc.contributor.organisationCentre for the Molecular Genetics of Development
dc.date.issued2000
dc.description.abstractSpondyloepiphyseal dysplasia tarda (SEDL) is an X-linked recessive disorder of endochondral bone formation caused by mutations in the SEDL gene. Here we present the structural analysis and subcellular localization of human SEDL. The SEDL gene is composed of six exons and spans a genomic region of ~20 kb in Xp22. It contains four Alu sequences in its 3′ UTR and an alternatively spliced MER20 sequence in its 5′ UTR (exon 2). Complex alternative splicing was detected for exon 4. Altogether seven SEDL pseudogenes were detected in the human genome: SEDLP1, a transcribed retropseudogene (or retro-xaptonuon) on chromosome 19q13.4 with potential to encode a protein identical to that of the SEDL gene; SEDLP2, another retropseudogene (not transcribed) on chromosome 8; and five truncated pseudogenes, SEDLP3–SEDLP7, on chromosome Yq11.23. Based on the knowledge of the yeast SEDL ortholog we speculated that the SEDL protein may participate along the ER-to-Golgi transport compartments. To test this hypothesis we performed transient transfection studies with tagged recombinant mammalian SEDL proteins in Cos-7 cells. The tagged SEDL proteins localized to perinuclear structures that partly overlapped with the intermediate ER–Golgi compartment (ERGIC; or vesicular tubular complex, VTC). Two human SEDL mutations (157–158delAT and C271T(STOP)) introduced into SEDL FLAG and GFP constructs led to the misplacement of the SEDL protein primarily to the cell nucleus and partially to the cytoplasm. Based on these experiments we suggest that the COOH end of the SEDL protein might be responsible for proper targeting of SEDL along the ER–Golgi membrane compartments (including Golgi and ERGIC/VTC).
dc.description.statementofresponsibilityJozef Gécz, Marie A. Hillman, Agi K. Gedeon, Timothy C. Cox, Elizabeth Baker and John C. Mulley
dc.description.urihttp://www.sciencedirect.com/science/journal/08887543
dc.identifier.citationGenomics, 2000; 69(2):242-251
dc.identifier.doi10.1006/geno.2000.6326
dc.identifier.issn0888-7543
dc.identifier.issn1089-8646
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]
dc.identifier.orcidHillman, M. [0000-0002-5060-190X]
dc.identifier.urihttp://hdl.handle.net/2440/7277
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.source.urihttps://doi.org/10.1006/geno.2000.6326
dc.subjectSubcellular Fractions
dc.subjectHumans
dc.subjectOsteochondrodysplasias
dc.subjectCarrier Proteins
dc.subjectMembrane Transport Proteins
dc.subjectRecombinant Proteins
dc.subjectTranscription Factors
dc.subjectAlternative Splicing
dc.subjectSequence Homology, Nucleic Acid
dc.subjectFrameshift Mutation
dc.subjectPseudogenes
dc.subjectGenome, Human
dc.subjectExpressed Sequence Tags
dc.titleGene structure and expression study of the SEDL gene for Spondyloepiphyseal Dysplasia Tarda
dc.typeJournal article
pubs.publication-statusPublished

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