Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits

G Zaboli; A Ameur; W Igl; A Johansson; C Hayward; V Vitart; S Campbell; L Zgaga; O Polasek; G Schmitz; Cornelia Duijn; Ben Oostra; P Pramstaller; A Hicks; T Meitinger; I Rudan; A Wright; JF Wilson; H Campbell; U Gyllensten

doi:10.1038/ejhg.2011.138

Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits

G Zaboli, A Ameur, W Igl, A Johansson, C Hayward, V Vitart, S Campbell, L Zgaga, O Polasek, G Schmitz, Cornelia Duijn, Ben Oostra, P Pramstaller, A Hicks, T Meitinger, I Rudan, A Wright, JF Wilson, H Campbell, U Gyllensten

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Scopus)

Abstract

We have used targeted genomic sequencing of high-complexity DNA pools based on long-range PCR and deep DNA sequencing by the SOLiD technology. The method was used for sequencing of 286 kb from four chromosomal regions with quantitative trait loci (QTL) influencing blood plasma lipid and uric acid levels in DNA pools of 500 individuals from each of five European populations. The method shows very good precision in estimating allele frequencies as compared with individual genotyping of SNPs (r(2) = 0.95, P < 10(-16)). Validation shows that the method is able to identify novel SNPs and estimate their frequency in high-complexity DNA pools. In our five populations, 17% of all SNPs and 61% of structural variants are not available in the public databases. A large fraction of the novel variants show a limited geographic distribution, with 62% of the novel SNPs and 59% of novel structural variants being detected in only one of the populations. The large number of population-specific novel SNPs underscores the need for comprehensive sequencing of local populations in order to identify the causal variants of human traits. European Journal of Human Genetics (2012) 20, 77-83; doi:10.1038/ejhg.2011.138; published online 3 August 2011

Original language	Undefined/Unknown
Pages (from-to)	77-83
Number of pages	7
Journal	European Journal of Human Genetics
Volume	20
Issue number	1
DOIs	https://doi.org/10.1038/ejhg.2011.138
Publication status	Published - 2012

Research programs

EMC MGC-02-96-01
EMC NIHES-01-64-02

Access to Document

10.1038/ejhg.2011.138

http://hdl.handle.net/1765/37208

Cite this

Zaboli, G., Ameur, A., Igl, W., Johansson, A., Hayward, C., Vitart, V., Campbell, S., Zgaga, L., Polasek, O., Schmitz, G., Duijn, C., Oostra, B., Pramstaller, P., Hicks, A., Meitinger, T., Rudan, I., Wright, A., Wilson, JF., Campbell, H., & Gyllensten, U. (2012). Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits. European Journal of Human Genetics, 20(1), 77-83. https://doi.org/10.1038/ejhg.2011.138

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title = "Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits",

abstract = "We have used targeted genomic sequencing of high-complexity DNA pools based on long-range PCR and deep DNA sequencing by the SOLiD technology. The method was used for sequencing of 286 kb from four chromosomal regions with quantitative trait loci (QTL) influencing blood plasma lipid and uric acid levels in DNA pools of 500 individuals from each of five European populations. The method shows very good precision in estimating allele frequencies as compared with individual genotyping of SNPs (r(2) = 0.95, P < 10(-16)). Validation shows that the method is able to identify novel SNPs and estimate their frequency in high-complexity DNA pools. In our five populations, 17% of all SNPs and 61% of structural variants are not available in the public databases. A large fraction of the novel variants show a limited geographic distribution, with 62% of the novel SNPs and 59% of novel structural variants being detected in only one of the populations. The large number of population-specific novel SNPs underscores the need for comprehensive sequencing of local populations in order to identify the causal variants of human traits. European Journal of Human Genetics (2012) 20, 77-83; doi:10.1038/ejhg.2011.138; published online 3 August 2011",

author = "G Zaboli and A Ameur and W Igl and A Johansson and C Hayward and V Vitart and S Campbell and L Zgaga and O Polasek and G Schmitz and Cornelia Duijn and Ben Oostra and P Pramstaller and A Hicks and T Meitinger and I Rudan and A Wright and JF Wilson and H Campbell and U Gyllensten",

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Zaboli, G, Ameur, A, Igl, W, Johansson, A, Hayward, C, Vitart, V, Campbell, S, Zgaga, L, Polasek, O, Schmitz, G, Duijn, C, Oostra, B, Pramstaller, P, Hicks, A, Meitinger, T, Rudan, I, Wright, A, Wilson, JF, Campbell, H & Gyllensten, U 2012, 'Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits', European Journal of Human Genetics, vol. 20, no. 1, pp. 77-83. https://doi.org/10.1038/ejhg.2011.138

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T1 - Sequencing of high-complexity DNA pools for identification of nucleotide and structural variants in regions associated with complex traits

AU - Zaboli, G

AU - Ameur, A

AU - Igl, W

AU - Johansson, A

AU - Hayward, C

AU - Vitart, V

AU - Campbell, S

AU - Zgaga, L

AU - Polasek, O

AU - Schmitz, G

AU - Duijn, Cornelia

AU - Oostra, Ben

AU - Pramstaller, P

AU - Hicks, A

AU - Meitinger, T

AU - Rudan, I

AU - Wright, A

AU - Wilson, JF

AU - Campbell, H

AU - Gyllensten, U

PY - 2012

Y1 - 2012

N2 - We have used targeted genomic sequencing of high-complexity DNA pools based on long-range PCR and deep DNA sequencing by the SOLiD technology. The method was used for sequencing of 286 kb from four chromosomal regions with quantitative trait loci (QTL) influencing blood plasma lipid and uric acid levels in DNA pools of 500 individuals from each of five European populations. The method shows very good precision in estimating allele frequencies as compared with individual genotyping of SNPs (r(2) = 0.95, P < 10(-16)). Validation shows that the method is able to identify novel SNPs and estimate their frequency in high-complexity DNA pools. In our five populations, 17% of all SNPs and 61% of structural variants are not available in the public databases. A large fraction of the novel variants show a limited geographic distribution, with 62% of the novel SNPs and 59% of novel structural variants being detected in only one of the populations. The large number of population-specific novel SNPs underscores the need for comprehensive sequencing of local populations in order to identify the causal variants of human traits. European Journal of Human Genetics (2012) 20, 77-83; doi:10.1038/ejhg.2011.138; published online 3 August 2011

AB - We have used targeted genomic sequencing of high-complexity DNA pools based on long-range PCR and deep DNA sequencing by the SOLiD technology. The method was used for sequencing of 286 kb from four chromosomal regions with quantitative trait loci (QTL) influencing blood plasma lipid and uric acid levels in DNA pools of 500 individuals from each of five European populations. The method shows very good precision in estimating allele frequencies as compared with individual genotyping of SNPs (r(2) = 0.95, P < 10(-16)). Validation shows that the method is able to identify novel SNPs and estimate their frequency in high-complexity DNA pools. In our five populations, 17% of all SNPs and 61% of structural variants are not available in the public databases. A large fraction of the novel variants show a limited geographic distribution, with 62% of the novel SNPs and 59% of novel structural variants being detected in only one of the populations. The large number of population-specific novel SNPs underscores the need for comprehensive sequencing of local populations in order to identify the causal variants of human traits. European Journal of Human Genetics (2012) 20, 77-83; doi:10.1038/ejhg.2011.138; published online 3 August 2011

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DO - 10.1038/ejhg.2011.138

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VL - 20

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JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

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