Directional genomic hybridization for chromosomal inversion discovery and detection

F. Andrew Ray, Erin Zimmerman, Bruce Robinson, Michael Cornforth, Joel S. Bedford, Edwin H. Goodwin, Susan M. Bailey

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Chromosomal rearrangements are a source of structural variation within the genome that figure prominently in human disease, where the importance of translocations and deletions is well recognized. In principle, inversions - reversals in the orientation of DNA sequences within a chromosome - should have similar detrimental potential. However, the study of inversions has been hampered by traditional approaches used for their detection, which are not particularly robust. Even with significant advances in whole genome approaches, changes in the absolute orientation of DNA remain difficult to detect routinely. Consequently, our understanding of inversions is still surprisingly limited, as is our appreciation for their frequency and involvement in human disease. Here, we introduce the directional genomic hybridization methodology of chromatid painting - a whole new way of looking at structural features of the genome - that can be employed with high resolution on a cell-by-cell basis, and demonstrate its basic capabilities for genome-wide discovery and targeted detection of inversions. Bioinformatics enabled development of sequence- and strand-specific directional probe sets, which when coupled with single-stranded hybridization, greatly improved the resolution and ease of inversion detection. We highlight examples of the far-ranging applicability of this cytogenomics-based approach, which include confirmation of the alignment of the human genome database and evidence that individuals themselves share similar sequence directionality, as well as use in comparative and evolutionary studies for any species whose genome has been sequenced. In addition to applications related to basic mechanistic studies, the information obtainable with strand-specific hybridization strategies may ultimately enable novel gene discovery, thereby benefitting the diagnosis and treatment of a variety of human disease states and disorders including cancer, autism, and idiopathic infertility.

Original languageEnglish (US)
Pages (from-to)165-174
Number of pages10
JournalChromosome Research
Volume21
Issue number2
DOIs
StatePublished - Apr 2013

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Nucleic Acid Hybridization
Genome
Genomic Structural Variation
Paintings
Chromatids
Genetic Association Studies
Human Genome
Autistic Disorder
Computational Biology
Infertility
Chromosomes
Databases
DNA
Neoplasms

Keywords

  • chromatid painting
  • chromosomal inversions
  • Strand-specific hybridization

ASJC Scopus subject areas

  • Genetics

Cite this

Ray, F. A., Zimmerman, E., Robinson, B., Cornforth, M., Bedford, J. S., Goodwin, E. H., & Bailey, S. M. (2013). Directional genomic hybridization for chromosomal inversion discovery and detection. Chromosome Research, 21(2), 165-174. https://doi.org/10.1007/s10577-013-9345-0

Directional genomic hybridization for chromosomal inversion discovery and detection. / Ray, F. Andrew; Zimmerman, Erin; Robinson, Bruce; Cornforth, Michael; Bedford, Joel S.; Goodwin, Edwin H.; Bailey, Susan M.

In: Chromosome Research, Vol. 21, No. 2, 04.2013, p. 165-174.

Research output: Contribution to journalArticle

Ray, FA, Zimmerman, E, Robinson, B, Cornforth, M, Bedford, JS, Goodwin, EH & Bailey, SM 2013, 'Directional genomic hybridization for chromosomal inversion discovery and detection', Chromosome Research, vol. 21, no. 2, pp. 165-174. https://doi.org/10.1007/s10577-013-9345-0
Ray, F. Andrew ; Zimmerman, Erin ; Robinson, Bruce ; Cornforth, Michael ; Bedford, Joel S. ; Goodwin, Edwin H. ; Bailey, Susan M. / Directional genomic hybridization for chromosomal inversion discovery and detection. In: Chromosome Research. 2013 ; Vol. 21, No. 2. pp. 165-174.
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