BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications

D. P. Locke, R. Segraves, R. D. Nicholls, S. Schwartz, D. Pinkel, Donna Albertson, E. E. Eichler

Research output: Contribution to journalArticle

Abstract

Chromosome 15q11-q13 is one of the most variable regions of the human genome, with numerous clinical rearrangements involving a dosage imbalance. Multiple clusters of segmental duplications are found in the pericentromeric region of 15q and at the breakpoints of proximal 15q rearrangements. Using sequence maps and previous global analyses of segmental duplications in the human genome, a targeted microarray was developed to detect a wide range of dosage imbalances in clinical samples. Clones were also chosen to assess the effect of paralogous sequences in the array format. In 19 patients analysed, the array data correlated with microsatellite and FISH characterisation. The data showed a linear response with respect to dosage, ranging from one to six copies of the region. Paralogous sequences in arrayed clones appear to respond to the total genomic copy number, and results with such clones may seem aberrant unless the sequence context of the arrayed sequence is well understood. The array CGH method offers exquisite resolution and sensitivity for detecting large scale dosage imbalances. These results indicate that the duplication composition of BAC substrates may affect the sensitivity for detecting dosage variation. They have important implications for effective microarray design, as well as for the detection of segmental aneusomy within the human population.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalJournal of Medical Genetics
Volume41
Issue number3
StatePublished - Mar 2004

Fingerprint

Genomic Segmental Duplications
Microarray Analysis
Clone Cells
Human Genome
Microsatellite Repeats
Chromosomes
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Locke, D. P., Segraves, R., Nicholls, R. D., Schwartz, S., Pinkel, D., Albertson, D., & Eichler, E. E. (2004). BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. Journal of Medical Genetics, 41(3), 175-182.

BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. / Locke, D. P.; Segraves, R.; Nicholls, R. D.; Schwartz, S.; Pinkel, D.; Albertson, Donna; Eichler, E. E.

In: Journal of Medical Genetics, Vol. 41, No. 3, 03.2004, p. 175-182.

Research output: Contribution to journalArticle

Locke, DP, Segraves, R, Nicholls, RD, Schwartz, S, Pinkel, D, Albertson, D & Eichler, EE 2004, 'BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications', Journal of Medical Genetics, vol. 41, no. 3, pp. 175-182.
Locke DP, Segraves R, Nicholls RD, Schwartz S, Pinkel D, Albertson D et al. BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. Journal of Medical Genetics. 2004 Mar;41(3):175-182.
Locke, D. P. ; Segraves, R. ; Nicholls, R. D. ; Schwartz, S. ; Pinkel, D. ; Albertson, Donna ; Eichler, E. E. / BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications. In: Journal of Medical Genetics. 2004 ; Vol. 41, No. 3. pp. 175-182.
@article{ef08149d322546b29e7a78351cbcd3d0,
title = "BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications",
abstract = "Chromosome 15q11-q13 is one of the most variable regions of the human genome, with numerous clinical rearrangements involving a dosage imbalance. Multiple clusters of segmental duplications are found in the pericentromeric region of 15q and at the breakpoints of proximal 15q rearrangements. Using sequence maps and previous global analyses of segmental duplications in the human genome, a targeted microarray was developed to detect a wide range of dosage imbalances in clinical samples. Clones were also chosen to assess the effect of paralogous sequences in the array format. In 19 patients analysed, the array data correlated with microsatellite and FISH characterisation. The data showed a linear response with respect to dosage, ranging from one to six copies of the region. Paralogous sequences in arrayed clones appear to respond to the total genomic copy number, and results with such clones may seem aberrant unless the sequence context of the arrayed sequence is well understood. The array CGH method offers exquisite resolution and sensitivity for detecting large scale dosage imbalances. These results indicate that the duplication composition of BAC substrates may affect the sensitivity for detecting dosage variation. They have important implications for effective microarray design, as well as for the detection of segmental aneusomy within the human population.",
author = "Locke, {D. P.} and R. Segraves and Nicholls, {R. D.} and S. Schwartz and D. Pinkel and Donna Albertson and Eichler, {E. E.}",
year = "2004",
month = "3",
language = "English (US)",
volume = "41",
pages = "175--182",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "3",

}

TY - JOUR

T1 - BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications

AU - Locke, D. P.

AU - Segraves, R.

AU - Nicholls, R. D.

AU - Schwartz, S.

AU - Pinkel, D.

AU - Albertson, Donna

AU - Eichler, E. E.

PY - 2004/3

Y1 - 2004/3

N2 - Chromosome 15q11-q13 is one of the most variable regions of the human genome, with numerous clinical rearrangements involving a dosage imbalance. Multiple clusters of segmental duplications are found in the pericentromeric region of 15q and at the breakpoints of proximal 15q rearrangements. Using sequence maps and previous global analyses of segmental duplications in the human genome, a targeted microarray was developed to detect a wide range of dosage imbalances in clinical samples. Clones were also chosen to assess the effect of paralogous sequences in the array format. In 19 patients analysed, the array data correlated with microsatellite and FISH characterisation. The data showed a linear response with respect to dosage, ranging from one to six copies of the region. Paralogous sequences in arrayed clones appear to respond to the total genomic copy number, and results with such clones may seem aberrant unless the sequence context of the arrayed sequence is well understood. The array CGH method offers exquisite resolution and sensitivity for detecting large scale dosage imbalances. These results indicate that the duplication composition of BAC substrates may affect the sensitivity for detecting dosage variation. They have important implications for effective microarray design, as well as for the detection of segmental aneusomy within the human population.

AB - Chromosome 15q11-q13 is one of the most variable regions of the human genome, with numerous clinical rearrangements involving a dosage imbalance. Multiple clusters of segmental duplications are found in the pericentromeric region of 15q and at the breakpoints of proximal 15q rearrangements. Using sequence maps and previous global analyses of segmental duplications in the human genome, a targeted microarray was developed to detect a wide range of dosage imbalances in clinical samples. Clones were also chosen to assess the effect of paralogous sequences in the array format. In 19 patients analysed, the array data correlated with microsatellite and FISH characterisation. The data showed a linear response with respect to dosage, ranging from one to six copies of the region. Paralogous sequences in arrayed clones appear to respond to the total genomic copy number, and results with such clones may seem aberrant unless the sequence context of the arrayed sequence is well understood. The array CGH method offers exquisite resolution and sensitivity for detecting large scale dosage imbalances. These results indicate that the duplication composition of BAC substrates may affect the sensitivity for detecting dosage variation. They have important implications for effective microarray design, as well as for the detection of segmental aneusomy within the human population.

UR - http://www.scopus.com/inward/record.url?scp=1542721515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542721515&partnerID=8YFLogxK

M3 - Article

VL - 41

SP - 175

EP - 182

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 3

ER -