Detection of mosaicism for genome imbalance in a cohort of 3,042 clinical cases using an oligonucleotide array CGH platform

Eur J Med Genet. Mar-Apr 2011;54(2):121-9. doi: 10.1016/j.ejmg.2010.10.010. Epub 2010 Nov 5.


Mosaicism for chromosome imbalance has traditionally been detected by karyotype analysis. The introduction of array CGH into clinical diagnostic laboratories and routine clinical practice has raised concerns as to the ability of this new test to detect the presence of more than one cell line. We present our validation data on the detection of chromosome mosaicism by oligonucleotide array CGH, and the cases detected in a cohort of 3042 clinical referrals. Using an artificial mosaicism series, we found that oligonucleotide array CGH using specific analysis parameters could accurately measure levels of mosaicism down to 10% and that the degree of mosaicism could be predicted from fluorescence ratios. We detected 12 cases of mosaicism in our clinical cohort, in 9 of which there was no previous indication of mosaicism. In two cases, G-banded chromosome analysis had been carried out previously, and had failed to detect the abnormal cell line. Three cases had mosaicism for the X chromosome and 9 involved autosomes, of which 4 were mosaic for whole chromosome trisomies, one for whole chromosome monosomy, and four were mosaic for segmental imbalances. We conclude that oligonucleotide array CGH has the power to detect a range of mosaic abnormalities in clinical diagnostic samples.

Publication types

  • Validation Study

MeSH terms

  • Chromosome Aberrations*
  • Comparative Genomic Hybridization / instrumentation
  • Comparative Genomic Hybridization / methods*
  • Humans
  • Loss of Heterozygosity
  • Mosaicism* / classification
  • Oligonucleotide Array Sequence Analysis / instrumentation*
  • Polyploidy