Biochemical and Biophysical Research Communications
A novel giant gene CSMD3 encoding a protein with CUB and sushi multiple domains: a candidate gene for benign adult familial myoclonic epilepsy on human chromosome 8q23.3–q24.1
Section snippets
Materials and methods
BAFME1/FAME patients. The DNA samples were obtained from healthy individuals and patients with BAFME1/FAME after receiving informed consent for this study [2], [3].
Construction of BAC contigs and sequencing. BAC contig of 30 Mb covering 8q22.1–q24.1 was constructed by digital hybridization method using Keio BAC library [7], [8]. These BAC clones were sequenced by shotgun sequencing method. We generated contiguous genomic sequence by combining our data with those generated by other sequencing
Identification of CSMD3 gene
We have sequenced and analyzed a BAC contig of 30 Mb corresponding to the 8q22–q24.1, within which the genetic locus of an epilepsy BAFME1/FAME has been mapped (Figs. 1A and B). Extensive computer-aided analysis with exon prediction programs revealed many potential exons, some of which encoded CUB and/or sushi domains (Fig. 1B). We integrated these predicted exons and formulated initially eight putative genes (CUB1–CUB8, data not shown). CUB1 showed significant homology to a cDNA clone KIAA1894,
Discussion
We identified a novel giant gene encoding a transmembrane protein with CUB and sushi multiple domains on the human chromosome 8q23.3–q24.1 in which benign adult familial myoclonic epilepsy type 1 (BAFME1/FAME, OMIM:601068) has been mapped. This giant gene consists of 73 exons and spans over 1.2 Mb on the genomic DNA region. Deduced amino acid sequence of the protein showed high homology to two other CSMD genes (CSMD1 on 8p23 and CSMD2 on 1p34) and hence this new gene was named as CSMD3. The
Acknowledgements
We thank T. Asakawa for her excellent technical assistance. This work was supported by the Fund for “Research for the Future” Program from the Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); and a Grant-in-Aid for Scientific Research from JSPS.
References (17)
- et al.
Localization of a gene for benign adult familial myoclonic epilepsy to chromosome 8q23.3–q24.1
Am. J. Hum. Genet.
(1999) - et al.
Linkage analysis between childhood absence epilepsy and genes encoding GABAA and GABAB receptors, voltage-dependent calcium channels, and the ECA1 region on chromosome 8q
Epilepsy Res.
(2002) - et al.
Human BAC library: construction and rapid screening
Gene
(1997) - et al.
High-fidelity digital hybridization screening
Genomics
(1998) - et al.
Transcript map of the 8p23 putative tumor suppressor region
Genomics
(2001) - et al.
The CUB domain. A widespread module in developmentally regulated proteins
J. Mol. Biol.
(1993) - et al.
Three-dimensional structure of a complement control protein module in solution
J. Mol. Biol.
(1991) - et al.
Localized expression of the seizure-related gene SEZ-6 in developing and adult forebrains
Mech. Dev.
(2002)
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Present address: Photon Medical Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.