Characterisation and expression analysis of the WDR9 gene, located in the Down critical region-2 of the human chromosome 21 Veronica C. Ramos a , Jose Manuel Vidal-Taboada a , Salvador Bergon ˜on a , Aliana Egeo b , Elizabeth M.C. Fisher c , Paolo Scartezzini b , Rafael Oliva a,d, * a Human Genetics Research Group, IDIBAPS, Faculty of Medicine, University of Barcelona, Casanova 143, 08023 Barcelona, Spain b Division of Pediatrics Hospital Galliera, Pediatric Service, Mura delle Capuccini Genoa 14, 4-16128, Italy c Neurogenetics Department, Imperial College, Norfolk Place, London, UK d Genetics Service, IDIBAPS, Hospital Clinic i Provincial, Villarroel 170, 08023, Barcelona, Spain Received 12 February 2002; received in revised form 29 May 2002; accepted 4 June 2002 Abstract We report the isolation and characterisation of the gene WDR9 (WD Repeat 9), located in the Down Syndrome critical region-2 (DCR-2) from the human chromosome 21. This gene spans 125 kb of genomic sequence and is organised in 41 exons and 40 introns. The WDR9 cDNA has a size of 13 kb and encodes for a putative protein of 2269 amino acids with a potential location in the nucleus. Expression analysis in different human adult tissues and in cultured cell lines indicates that the gene has several tissue-specific transcripts. The more significant protein signatures in the WDR9 protein sequence are for WD repeats, bromodomain, beta-ketoacyl synthases, and ribonucleoprotein (RNP). The WDR9 protein has a high similarity with the Mus musculus neuronal differentiation protein (NDRP) and a region of similarity with the region of the Yotiao protein that has been proposed to bind the NR1 subunit of the NMDA receptor. The presence of protein–protein interaction domains as such the WD repeats, and the similarity of the WDR9 protein to regulatory proteins suggest a potential involvement in some of the clinical features associated to the DCR-2. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Down Syndrome; WD repeats; Expression analysis; 21q22; Down critical region; WDR9 Down Syndrome (DS) is usually caused by a full trisomy of chromosome 21, although a subset of the patients that carry only a partial trisomy of chromosome 21 also exhibit some of its features [1]. The partial trisomy of the region that includes D21S55 and MX1 markers on sub-bands 21q22.2 and 21q22.3 has been associated with different features of DS [2]. This chromosomal region has been postulated as the minimal region for six facial and dermato- glyphic features and, in some patients, the region is appa- rently determinant of the pathogenesis of mental retardation, congenital heart disease, and duodenal stenosis [3,4]. This region is known as the Down syndrome critical region-2 (DCR-2) [2]. As part of an effort to isolate, characterise and map the genes potentially responsible for some of the DS features, we have constructed high-resolution physical maps [5] and transcriptional maps [6] in the DCR-2 region. This approach has allowed us to locate and characterise several genes such as the SH3BGR gene [7] and the DSCR2 gene [8]. In addition, we had also isolated and located several additional transcription units in this region from human chromosome 21 [6]. Three previously mapped cDNAs, 903H1 (AJ222636), N143 (AJ002572), and N144 (AJ002574) [5,6], located in the A1047 cosmid clone and in the PAC clone 31K18 (Fig. 1), were used as the starting material in the present work. To determine whether these cDNAs were part of the same gene, the draft genomic sequence AF129408 was used to BLAST for new EST sequences, which were purchased and sequenced to completion. The sequences obtained were then assembled into three large sequences contigs and deposited to GenBank: 903H1, HGG-3 (AJ238554) and HGG-4 (AJ238555). Concomitant to the development of the present work, the PAC clone 31K18, which we had also previously mapped to the DCR2 region [5], entered in the genome sequencing project by the German Human Genome Project 0167-4781/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII:S0167-4781(02)00421-9 * Corresponding author. Human Genetics Research Group, Faculty of Medicine, University of Barcelona, Casanova 143, 08036 Barcelona, Spain. Tel.: +34-93-4021877; fax: +34-93-4035260. E-mail address: oliva@medicina.ub.es (R. Oliva). www.bba-direct.com Biochimica et Biophysica Acta 1577 (2002) 377 – 383