Elsevier

Genomics

Volume 81, Issue 6, June 2003, Pages 560-569
Genomics

Regular article
Characterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant☆

https://doi.org/10.1016/S0888-7543(03)00091-0Get rights and content

Abstract

Oral–facial–digital type 1 (OFD1) syndrome is an X-linked dominant condition characterized by malformations of the face, oral cavity, and digits. The responsible gene, OFD1, maps to human Xp22 and has an unknown function. We isolated and characterized the mouse Ofd1 gene and showed that it is subject to X-inactivation, in contrast to the human gene. Furthermore, we excluded a role for Ofd1 in the pathogenesis of the spontaneous mouse mutant Xpl, which had been proposed as a mouse model for this condition. Comparative sequence analysis demonstrated that OFD1 is conserved among vertebrates and absent in invertebrates. This analysis allowed the identification of evolutionarily conserved domains in the protein. Finally, we report the identification of 18 apparently nonfunctional OFD1 copies, organized in repeat units on the human Y chromosome. These degenerate OFD1-Y genes probably derived from the ancestral Y homologue of the X-linked gene. The high level of sequence identity among the different units suggests that duplication events have recently occurred during evolution.

Section snippets

Identification of the mouse Ofd1 gene

To identify the mouse homologue of the OFD1 gene, the human cDNA sequence was used as a query in a BLAST search against the mouse EST database. Four EST clones (Accession Nos. AI839356, AI508554, AI549645, and AA240611) were found to share significant sequence similarity with the OFD1 cDNA. Sequence analysis of these clones revealed that they likely contained partial sequences corresponding to the 5′ and 3′ ends of the mouse Ofd1 transcript. IMAGE Clone 822465 (Accession No. AI549645) was then

Discussion

We have previously shown that oral–facial–digital type 1 syndrome is caused by mutations in the OFD1 gene [13]. However, little is known of the gene function. To gain insight into OFD1 function, we have cloned and characterized the mouse homologue of OFD1 and found that it shares 71% identity with the human gene. The mouse and human Ofd1/OFD1 genes have similar genomic structures that span a larger genomic region (50 kb) in mouse, compared to human (35 kb). In addition, the genes are expressed

cDNA identification and genomic structure

We identified the mouse homologue of the OFD1 gene by assembling the sequence data obtained from: (i) sequencing of four EST clones homologous to the human cDNA, (ii) characterization of clones isolated from the screening of a mouse retina cDNA library, and (iii) sequencing of a RT-PCR fragment amplified on mouse lung RNA. The mouse retina cDNA library (Lambda ZAP) was screened with one of the ESTs as a probe. Plating, hybridization, and washing conditions were as previously described [31].

Acknowledgements

This work was supported by the Italian Telethon Foundation (B.F.), by the EC under Grant QLRT-1999-00791 (B.F.), and by a grant from the National Institutes of Health, GM 46883 (C.D.). We thank the TIGEM sequencing core facility for technical support.

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    Sequence data from this article have been deposited with the EMBL Data Library under Accession Nos. AJ438159, AJ534306, and AJ512827.

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