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 log2 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.
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Acknowledgements
We are grateful to Dr. Masahiro Ito and Dr. Fumiko Saito-Ohara for a useful discussion on a patient with DMD and PMD. We also thank Ms. Ayako Takahashi and Ms. Rumi Mori for their technical assistance. This study was supported by Grants-in-Aid for Scientific Research on Priority Areas and 21st Century Center of Excellence Program for Molecular Destruction and Reconstitution of Tooth and Bone from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; and by a Grant-in-Aid from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation (JST).
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Hayashi, S., Honda, S., Minaguchi, M. et al. Construction of a high-density and high-resolution human chromosome X array for comparative genomic hybridization analysis. J Hum Genet 52, 397–405 (2007). https://doi.org/10.1007/s10038-007-0127-4
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DOI: https://doi.org/10.1007/s10038-007-0127-4
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