Development of array based comparative genomic hybridization (CGH) as a diagnostic tool for cryptic chromosome aberrations in congenital disorders

开发基于阵列的比较基因组杂交（CGH）作为先天性疾病中隐性染色体畸变的诊断工具

基本信息

批准号：
17390099
负责人：
INAZAWA Johji
金额：
$ 9.34万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390099/
关键词：
Congenital anomaly Mental retardation Autism Chromosome aberration Microarray CGH Diagnostic tool BAC

项目摘要

The human genome sequencing project had been conducted successfully, with 99% of the genome sequenced with 99.99% accuracy. In the post-sequence era, detection of disease-related genomic alterations is directly connected with identification of genes associated with multiple congenital anomalies with mental retardation (MCA/MR), autism, and other unknown genomic disorders. However, we had none of tools for exploring cryptic chromosome aberrations at 100kb-level. In order to overcome the situation, we have constructed high-resolution CGH-arrays as follows, (1) Whole Genome Array (WGA)-4500, which contains 4523 BACs throughout the whole genome, (2) Cancer Array-800, which harbors 800 BACs for different cancer-related genes, (3) 1p36-contig array, which covers about 20Mb spanning 1p36 region with 212 BACs, (4) Chromosome X-tiling array, which contains 1001 BACs throughout chromosome X except pseudo-autosomal region, and (5) Genome Disorder (GD)-array, which is employed as the diagnostic tool for known genomic disorders. Using those in-house BAC arrays, we explored cryptic chromosome aberrations in a large number of patients with MCA/MR, and detected de novo submicroscopic aberrations related to the pathogenesis of unknown MCA/MR in some of those patients.

人类基因组测序工程已成功实施，99%的基因组已测序，准确率达到99.99%。在后测序时代，检测与疾病相关的基因组改变与识别与智力低下（MCA/MR）、自闭症和其他未知基因组疾病等多种先天性异常相关的基因直接相关。然而，我们没有任何工具可以在 100kb 水平上探索神秘的染色体畸变。为了克服这种情况，我们构建了如下高分辨率 CGH 阵列，(1) 全基因组阵列 (WGA)-4500，其中包含整个基因组中的 4523 个 BAC，(2) Cancer Array-800，其中包含800 个针对不同癌症相关基因的 BAC，(3) 1p36-contig 阵列，覆盖约 20Mb，跨越 1p36 区域，包含 212 个BAC，(4) 染色体 X 平铺阵列，除伪常染色体区域外，在整个 X 染色体上包含 1001 个 BAC，以及 (5) 基因组疾病 (GD) 阵列，用作已知基因组疾病的诊断工具。使用这些内部 BAC 阵列，我们探索了大量 MCA/MR 患者的隐性染色体畸变，并在其中一些患者中检测到与未知 MCA/MR 发病机制相关的从头亚显微畸变。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease.

DOI：
发表时间：
2006
期刊：
Annals of neurology
影响因子：
11.2
作者：
K. Nishioka;Shin Hayashi;M. Farrer;A. Singleton;H. Yoshino;H. Imai;Toshiaki Kitami;Kenichi Sato;R. Kuroda;H. Tomiyama;K. Mizoguchi;M. Murata;T. Toda;I. Imoto;J. Inazawa;Y. Mizuno;N. Hattori
通讯作者：
K. Nishioka;Shin Hayashi;M. Farrer;A. Singleton;H. Yoshino;H. Imai;Toshiaki Kitami;Kenichi Sato;R. Kuroda;H. Tomiyama;K. Mizoguchi;M. Murata;T. Toda;I. Imoto;J. Inazawa;Y. Mizuno;N. Hattori

Clinical and molecular cytogenetic characterization od two patients with non-mutational aberrations of the FMR2 gene.

两名 FMR2 基因非突变畸变患者的临床和分子细胞遗传学特征。