Regular articleCharacterization of the OFD1/Ofd1 genes on the human and mouse sex chromosomes and exclusion of Ofd1 for the Xpl mouse mutant☆☆
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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2022, European Journal of Medical GeneticsCitation Excerpt :The main transcript (OFD1a) encodes a 1011 amino acid, centriole and centriolar satellite protein that is ubiquitously expressed during human organogenesis (Romio, 2003) as well as in adult organs (de Conciliis et al.,). The protein product is predicted to have an N-terminal LisH domain and 5 coiled-coil domains, and it localizes to the basal body at the centrosome of primary cilia (Romio, 2003; Ferrante et al., 2003) where it is involved in the formation of primary cilia (ciliogenesis) and in left-to-right specification. Additionally, the OFD1 protein also has several intrinsically disordered regions (IDRs) which may serve to enhance protein-protein interactions (Babu, 2016).
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2015, Current Topics in Developmental BiologyOfd1 is required in limb bud patterning and endochondral bone development
2011, Developmental BiologyCitation Excerpt :These clinical features overlap with those reported in other forms of OFDS (Gurrieri et al., 2007), although the X-linked dominant inheritance pattern and the presence of cystic kidneys are distinctive features specific to OFD type I. Limb abnormalities have been described in over 90% of patients bearing mutations in the OFD1 transcripts and include syndactyly, brachydactyly, clynodactyly, unilateral duplication of the hallux, and, more rarely, pre- or postaxial polydactyly (Prattichizzo et al., 2008; Thauvin-Robinet et al., 2006). The gene responsible for this genetic disorder, named OFD1, is expressed during embryonic development and in postnatal tissues of all affected structures, in both human and mouse (de Conciliis et al., 1998; Ferrante et al., 2003; Ferrante et al., 2001). OFD1 encodes for a 1011-amino-acid protein characterized by the presence of five predicted CC domains that occupy almost the entire length of the molecule and a Lis1 homology motif (LisH), shared with over 100 eukaryotic intracellular proteins, at the N-terminal region (Emes and Ponting, 2001; Gerlitz et al., 2005).
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Sequence data from this article have been deposited with the EMBL Data Library under Accession Nos. AJ438159, AJ534306, and AJ512827.