Dataset Information

Identification of medium-sized genomic deletions with low coverage, mate-paired restricted tags.

ABSTRACT: BACKGROUND: Genomic deletions are known to be widespread in many species. Variant sequencing-based approaches for identifying deletions have been developed, but their powers to detect those deletions that affect medium-sized regions are limited when the sequencing coverage is low. RESULTS: We present a cost-effective method for identifying medium-sized deletions in genomic regions with low genomic coverage. Two mate-paired libraries were separately constructed from human cancerous tissue to generate paired short reads (ditags) from restriction fragments digested with a 4-base restriction enzyme. A total of 3 Gb of paired reads (1.0× genome size) was collected, and 175 deletions were inferred by identifying the ditags with disorder alignments to the reference genome sequence. Sanger sequencing results confirmed an overall detection accuracy of 95%. Good reproducibility was verified by the deletions that were detected by both libraries. CONCLUSIONS: We provide an approach to accurately identify medium-sized deletions in large genomes with low sequence coverage. It can be applied in studies of comparative genomics and in the identification of germline and somatic variants.

SUBMITTER: Gong Q

PROVIDER: S-EPMC3608957 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Identification of medium-sized genomic deletions with low coverage, mate-paired restricted tags.

Gong Qiang Q Tao Yong Y Yang Jian-Rong JR Cai Jun J Yuan Yunfei Y Ruan Jue J Yang Jin J Liu Hailiang H Li Wanghua W Lu Xuemei X Zhuang Shi-Mei SM Wang San Ming SM Wu Chung-I CI

BMC genomics 20130124

<h4>Background</h4>Genomic deletions are known to be widespread in many species. Variant sequencing-based approaches for identifying deletions have been developed, but their powers to detect those deletions that affect medium-sized regions are limited when the sequencing coverage is low.<h4>Results</h4>We present a cost-effective method for identifying medium-sized deletions in genomic regions with low genomic coverage. Two mate-paired libraries were separately constructed from human cancerous t ...[more]

PMID: 23347462

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Project description:BackgroundGenome- and population-wide re-sequencing would allow for most efficient detection of causal trait variants. However, despite a strong decrease of costs for next-generation sequencing in the last few years, re-sequencing of large numbers of individuals is not yet affordable. We therefore resorted to re-sequencing of a limited number of bovine animals selected to explain a major proportion of the population's genomic variation, so called key animals, in order to provide a catalogue of functional variants and a substrate for population- and genome-wide imputation of variable sites.ResultsForty-three animals accounting for about 69 percent of the genetic diversity of the Fleckvieh population, a cattle breed of Southern Germany and Austria, were sequenced with coverages ranging from 4.17 to 24.98 and averaging 7.46. After alignment to the reference genome (UMD3.1) and multi-sample variant calling, more than 17 million variant positions were identified, about 90 percent biallelic single nucleotide variants (SNVs) and 10 percent short insertions and deletions (InDels). The comparison with high-density chip data revealed a sensitivity of at least 92 percent and a specificity of 81 percent for sequencing based genotyping, and 97 percent and 93 percent when a imputation step was included. There are 91,733 variants in coding regions of 18,444 genes, 46 percent being non-synonymous exchanges, of which 575 variants are predicted to cause premature stop codons. Three variants are listed in the OMIA database as causal for specific phenotypes.ConclusionsLow- to medium-coverage re-sequencing of individuals explaining a major fraction of a population's genomic variation allows for the efficient and reliable detection of most variants. Imputation strongly improves genotype quality of lowly covered samples and thus enables maximum density genotyping by sequencing. The functional annotation of variants provides the basis for exhaustive genotype imputation in the population, e.g., for highest-resolution genome-wide association studies.

Dataset Information

Identification of medium-sized genomic deletions with low coverage, mate-paired restricted tags.

Publications

Identification of medium-sized genomic deletions with low coverage, mate-paired restricted tags.

Similar Datasets

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