Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array

Teresita Díaz de Ståhl; Johanna Sandgren; Arkadiusz Piotrowski; Helena Nord; Robin Andersson; Uwe Menzel; Adam Bogdan; Ann-Charlotte Thuresson; Andrzej Poplawski; Desiree von Tell; Caisa M Hansson; Amir I Elshafie; Gehad Elghazali; Stephan Imreh; Magnus Nordenskjöld; Meena Upadhyaya; Jan Komorowski; Carl E G Bruder; Jan P Dumanski

doi:10.1002/humu.20659

Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array

Teresita Díaz de Ståhl, Johanna Sandgren, Arkadiusz Piotrowski, Helena Nord, Robin Andersson, Uwe Menzel, Adam Bogdan, Ann-Charlotte Thuresson, Andrzej Poplawski, Desiree von Tell, Caisa M Hansson, Amir I Elshafie, Gehad Elghazali, Stephan Imreh, Magnus Nordenskjöld, Meena Upadhyaya, Jan Komorowski, Carl E G Bruder, Jan P Dumanski

43 Citations (Scopus)

Abstract

To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.

Original language	English
Journal	Human Mutation
Volume	29
Issue number	3
Pages (from-to)	398-408
Number of pages	11
ISSN	1059-7794
DOIs	https://doi.org/10.1002/humu.20659
Publication status	Published - Mar 2008
Externally published	Yes

Keywords

African Continental Ancestry Group
Algorithms
Asian Continental Ancestry Group
Chromosomes, Artificial, Bacterial
Chromosomes, Human, X
Continental Population Groups
European Continental Ancestry Group
Female
Gene Dosage
Gene Duplication
Gene Rearrangement
Genetic Variation
Genome, Human
Humans
Male
Markov Chains
Oligonucleotide Array Sequence Analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/humu.20659

Cite this

Díaz de Ståhl, T., Sandgren, J., Piotrowski, A., Nord, H., Andersson, R., Menzel, U., Bogdan, A., Thuresson, A.-C., Poplawski, A., von Tell, D., Hansson, C. M., Elshafie, A. I., Elghazali, G., Imreh, S., Nordenskjöld, M., Upadhyaya, M., Komorowski, J., Bruder, C. E. G., & Dumanski, J. P. (2008). Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array. Human Mutation, 29(3), 398-408. https://doi.org/10.1002/humu.20659

Díaz de Ståhl, T, Sandgren, J, Piotrowski, A, Nord, H, Andersson, R, Menzel, U, Bogdan, A, Thuresson, A-C, Poplawski, A, von Tell, D, Hansson, CM, Elshafie, AI, Elghazali, G, Imreh, S, Nordenskjöld, M, Upadhyaya, M, Komorowski, J, Bruder, CEG & Dumanski, JP 2008, 'Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array', Human Mutation, vol. 29, no. 3, pp. 398-408. https://doi.org/10.1002/humu.20659

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title = "Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array",

abstract = "To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.",

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T1 - Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array

AU - Díaz de Ståhl, Teresita

AU - Sandgren, Johanna

AU - Piotrowski, Arkadiusz

AU - Nord, Helena

AU - Andersson, Robin

AU - Menzel, Uwe

AU - Bogdan, Adam

AU - Thuresson, Ann-Charlotte

AU - Poplawski, Andrzej

AU - von Tell, Desiree

AU - Hansson, Caisa M

AU - Elshafie, Amir I

AU - Elghazali, Gehad

AU - Imreh, Stephan

AU - Nordenskjöld, Magnus

AU - Upadhyaya, Meena

AU - Komorowski, Jan

AU - Bruder, Carl E G

AU - Dumanski, Jan P

PY - 2008/3

Y1 - 2008/3

N2 - To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.

AB - To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.

KW - African Continental Ancestry Group

KW - Algorithms

KW - Asian Continental Ancestry Group

KW - Chromosomes, Artificial, Bacterial

KW - Chromosomes, Human, X

KW - Continental Population Groups

KW - European Continental Ancestry Group

KW - Female

KW - Gene Dosage

KW - Gene Duplication

KW - Gene Rearrangement

KW - Genetic Variation

KW - Genome, Human

KW - Humans

KW - Male

KW - Markov Chains

KW - Oligonucleotide Array Sequence Analysis

U2 - 10.1002/humu.20659

DO - 10.1002/humu.20659

M3 - Journal article

C2 - 18058796

SN - 1059-7794

VL - 29

SP - 398

EP - 408

JO - Human Mutation

JF - Human Mutation

IS - 3

ER -

Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array

Abstract

Keywords

UN SDGs

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