title: Construction of a high-density and high-resolution human chromosome X array for comparative genomic hybridization analysis.
abstract: The human chromosome X is closely associated with congenital disorders and mental retardation (MR), because it contains a significantly higher number of genes than estimated from the proportion in the human genome. We constructed a high-density and high-resolution human chromosome X array (X-tiling array) for comparative genomic hybridization (CGH). The array contains a total of 1,001 bacterial artificial chromosome (BACs) throughout chromosome X except pseudoautosomal regions and two BACs specific for Y. In four hybridizations using DNA samples from healthy males, the ratio of each spotted DNA was scattered between -3SD and 3SD, corresponding to a log(2) ratio of -0.35 and 0.35, respectively. Using DNA samples from patients with known congenital disorders, our X-tiling array was proven to discriminate one-copy losses and gains together with their physical sizes, and also to estimate the percentage of a mosaicism in a patient with mos 45,X[13]/46,X,r(X)[7]. Furthermore, array-CGH in a patient with atypical Schinzel-Giedion syndrome disclosed a 1.1-Mb duplication at Xq22.3 including a part of the IL1RAPL2 gene as a likely causative aberration. The results indicate our in-house X-tiling array to be useful for the identification of cryptic copy-number aberrations containing novel genes responsible for diseases such as congenital disorders and X-linked MR.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.|Department of Pediatric and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan.|Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), 4-1-8 Hon-machi Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.|Department of Pediatric and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan.|Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), 4-1-8 Hon-machi Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Honda
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.|Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), 4-1-8 Hon-machi Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Minaguchi
authors.affiliation: Department of Pediatrics, Asahikawa Medical Collage, Midorigaoka-Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.affiliation: Department of Planning and Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Murodocho 840, Izumi, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Kosaki
authors.affiliation: Department of Clinical Genetics and Molecular Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.|Hard Tissue Genome Research Center, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan.|Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), 4-1-8 Hon-machi Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.affiliation: Department of Pediatric and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. johinaz.cgen@mri.tmd.ac.jp.|Hard Tissue Genome Research Center, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan. johinaz.cgen@mri.tmd.ac.jp.|21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8510, Japan. johinaz.cgen@mri.tmd.ac.jp.|Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Corporation (JST), 4-1-8 Hon-machi Kawaguchi, Saitama, 332-0012, Japan. johinaz.cgen@mri.tmd.ac.jp.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D022202:Chromosomes, Artificial, Bacterial; D041321:Chromosomes, Human, X; D018628:Gene Dosage; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods*; D009693:Nucleic Acid Hybridization
chemical_list: C407644:IL1RAPL2 protein, human; D053577:Interleukin-1 Receptor Accessory Protein