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Euchromatic 9q13-q21 duplication variants are tandem segmental amplifications of sequence reciprocal to 9q13-q21 deletions
  1. Ann M Joseph-George1,2,
  2. Yongshu He1,
  3. Christian R Marshall1,
  4. Raymond C C Wong1,
  5. Jeffrey R MacDonald1,
  6. Ciara A Fahey1,
  7. David Chitayat3,4,
  8. Kathy Chun4,5,
  9. Greg Ryan4,6,
  10. Anne M Summers5,
  11. Elizabeth J T Winsor4,7,
  12. Stephen W Scherer1,4,8
  1. 1The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada
  2. 2Department of Paediatric Laboratory Medicine, Cytogenetics Laboratory, The Hospital for Sick Children, Toronto, Ontario, Canada
  3. 3Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, Toronto, Ontario, Canada
  4. 4University of Toronto, Ontario, Canada
  5. 5Genetics Program, North York General Hospital, Toronto, Ontario, Canada
  6. 6Fetal Medicine Unit, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada
  7. 7Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
  8. 8McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Stephen W Scherer, The Centre for Applied Genomics, The Hospital for Sick Children, 14th Floor, Toronto Medical Discovery Tower/MaRS Discovery District, 101 College Street, Toronto, Ontario, M5G 1L7, Canada; stephen.scherer{at}


Background There are four known pericentromeric euchromatic variants of chromosome 9 in the literature that are increasingly being observed in diagnostic cytogenetic laboratories. These variants pose diagnostic and counselling dilemmas, especially in prenatal settings, as distinction of a pathogenic alteration from a euchromatic variant is difficult. The molecular characterisation of three of these four variants has been reported. In this study, the genomic structure of the fourth variant, an additional G-positive band at 9q13-q21, is characterised.

Methods Two unrelated families with the 9q13-q21 duplication variant, and a third individual with a cytogenetically visible 9q13-q21 deletion, were studied using conventional and molecular cytogenetics techniques, as well as microarrays. The highly repetitive nature of the segmental duplications in the region also necessitated the use of both interphase and metaphase fluorescence in situ hybridisation (FISH).

Results It was determined that the DNA that constitutes this variant was ∼15–20 megabases in size and tandemly repeated as 3–4 cassettes of intrachromosomal segmental duplication. The variant appeared constitutively similar in sequence content and organisation between the two unrelated individuals, and it was inherited without apparent change. Sequences found amplified in the two duplication carriers were absent in the carrier of the deletion variant.

Conclusions The sequences involved in both the 9q13-q21 duplication and deletion appear the same, implying reciprocity and suggesting non-allelic homologous recombination as the underlying mechanism. All four known euchromatic variants of chromosome 9 have now been shown to encompass segmental duplications. Importantly, a set of validated FISH probes was defined for the detection and characterisation of this 9q13-q21 amplification in the context of other chromosome 9 variants, allowing apparently benign variants to be distinguished from pathogenic changes.

  • 9q13-q21
  • Euchromatic variant
  • segmental duplication
  • diagnostics tests
  • genetics
  • clinical genetics
  • cytogenetics
  • molecular genetics

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  • Dr Anne M Summers died on 14th March 2009.

  • Funding The work is supported by Genome Canada/Ontario Genomics Institute, the Canadian Institutes of Health Research (CIHR), the McLaughlin Centre, the Canadian Institute of Advanced Research, and The Hospital for Sick Children (SickKids) Foundation.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the REB, Mt Sinai Hospital, Toronto, Ontario, Canada.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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