Elsevier

Genomics

Volume 43, Issue 2, 15 July 1997, Pages 115-122
Genomics

Regular Article
The Human Homogentisate 1,2-Dioxygenase (HGO) Gene,☆☆

https://doi.org/10.1006/geno.1997.4805Get rights and content

Abstract

Alkaptonuria (AKU; McKusick No. 203500), a rare hereditary disorder of the phenylalanine catabolism, was the first disease to be interpreted as an inborn error of metabolism (A. E. Garrod, 1902,Lancet2: 1616–1620). AKU patients are deficient for homogentisate 1,2-dioxygenase (HGO; EC 1.13.11.5). This enzymatic deficiency causes homogentisic aciduria, ochronosis, and arthritis. Recently we cloned the humanHGOgene and showed that AKU patients carry two copies of a loss-of-functionHGOallele. Here we describe the complete nucleotide sequence of the humanHGOgene and the identification of its promoter region. The humanHGOgene spans 54,363 bp and codes for a 1715-nt-long transcript that is split into 14 exons ranging from 35 to 360 bp. TheHGOintrons, 605 to 17,687 bp in length, contain representatives of the major classes of repetitive elements, including several simple sequence repeats (SSR). Two of these SSRs, a (CT)nrepeat in intron 4 and a (CA)nrepeat in intron 13, were found to be polymorphic in a Spanish population sample. TheHGOtranscription start site was determined by primer extension. We report that sequences from −1074 to +89 bp (relative to theHGOtranscription start site) are sufficient to promote transcription of a CAT reporter gene in human liver cells and that this fragment contains putative binding sites for liver-enriched transcription factors that might be involved in the regulation ofHGOexpression in liver.

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    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. AF000573.

    ☆☆

    D. M. Glover, Ed.

    1

    B.G., D.B.-V. de B., and J.M.F-C. contributed equally to this work.

    2

    To whom correspondence should be addressed at the Departamento de Inmunologı́a, Centro de Investigaciones Biológicas Consejo Superior de Investigaciones Cientı́ficas, Velázquez 144, 28006 Madrid, Spain. Fax: (341)-5627518. E-mail: SRdeC@pinar1. csic.es.

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