Sensitive and specific detection of mosaic chromosomal abnormalities using the Parent-of-Origin-based Detection (POD) method

Joseph D. Baugher, Benjamin D. Baugher, Matthew D. Shirley, Jonathan Pevsner

Research output: Contribution to journalArticle

Abstract

Background: Mosaic somatic alterations are present in all multi-cellular organisms, but the physiological effects of low-level mosaicism are largely unknown. Most mosaic alterations remain undetectable with current analytical approaches, although the presence of such alterations is increasingly implicated as causative for disease.Results: Here, we present the Parent-of-Origin-based Detection (POD) method for chromosomal abnormality detection in trio-based SNP microarray data. Our software implementation, triPOD, was benchmarked using a simulated dataset, outperformed comparable software for sensitivity of abnormality detection, and displayed substantial improvement in the detection of low-level mosaicism while maintaining comparable specificity. Examples of low-level mosaic abnormalities from a large autism dataset demonstrate the benefits of the increased sensitivity provided by triPOD. The triPOD analyses showed robustness across multiple types of Illumina microarray chips. Two large, clinically-relevant datasets were characterized and compared.Conclusions: Our method and software provide a significant advancement in the ability to detect low-level mosaic abnormalities, thereby opening new avenues for research into the implications of mosaicism in pathogenic and non-pathogenic processes.

Original languageEnglish (US)
Article number367
JournalBMC genomics
Volume14
Issue number1
DOIs
StatePublished - May 31 2013

Keywords

  • Autism
  • Cleft
  • HapMap
  • Microarray
  • Mosaicism
  • Parent-child
  • Parent-of-origin
  • Software
  • Trio

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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