Short Communication

Journal of Human Genetics (1999) 44, 330–336; doi:10.1007/s100380050171

Complete cDNA sequence and genomic organization of a human pancreas-specific gene homologous to Caenorhabditis elegans sel-1

Yosuke Harada1, Kouichi Ozaki1, Mikio Suzuki1, Tsutomu Fujiwara1, Ei-ichi Takahashi1, Yusuke Nakamura2 and Akira Tanigami1

  1. 1Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
  2. 2Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Correspondence: Akira Tanigami, Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan. Fax: +81-88-637-1035. E-mail: atanigam@otsuka.gr.jp

Received 29 March 1999; Accepted 11 May 1999.

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Abstract

We have isolated the complete cDNA of a human SEL-1L gene, termed TSA305, that is abundantly expressed only in the pancreas. The cDNA contained an open reading frame of 2382 nucleotides, encoding a deduced protein of 794 amino acids whose predicted sequence showed 46% identity and 64% similarity with SEL-1 of Caenorhabditis elegans. SEL-1 is thought to be a negative regulator of the NOTCH, LIN-12, and GLP-1 receptors, which are required for differentiation and maturation of cells as well as cell-cell interactions during development in C. elegans. The degree of homology among these proteins suggests that the TSA305 gene product may be a member of the SEL-1 family and therefore involved in downregulation of mammalian Notch signaling. Direct sequencing revealed at least 20 coding exons in TSA305. We localized the gene to chromosome bands 14q24.3–q31 by radiation hybrid (RH) mapping and fluorescence in situ hybridization (FISH). The IDDM11 locus has been mapped in this region, and TSA305 may represent a candidate gene for predisposition in some families whose insulin-dependent diabetes is not linked to the HLA locus.

Keywords:

Pancreas-specific gene, SEL-1, SEL-1L, Notch signaling, IDDM11, 14q24.3-q31