Construction of a high-density and high-resolution human chromosome X array for comparative genomic hybridization analysis

J Hum Genet. 2007;52(5):397-405. doi: 10.1007/s10038-007-0127-4. Epub 2007 Apr 4.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Artificial, Bacterial
  • Chromosomes, Human, X*
  • Gene Dosage
  • Genetic Diseases, X-Linked / genetics*
  • Humans
  • Interleukin-1 Receptor Accessory Protein / genetics
  • Male
  • Mental Retardation, X-Linked / genetics
  • Microarray Analysis / methods*
  • Nucleic Acid Hybridization*

Substances

  • IL1RAPL2 protein, human
  • Interleukin-1 Receptor Accessory Protein