Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jan 10;4(1):63-5.
doi: 10.1534/g3.113.008797.

Performance of high-throughput sequencing for the discovery of genetic variation across the complete size spectrum

Andy Wing Chun Pang  1 , Jeffrey R Macdonald, Ryan K C Yuen, Vanessa M Hayes, Stephen W Scherer
Affiliations

Performance of high-throughput sequencing for the discovery of genetic variation across the complete size spectrum

Andy Wing Chun Pang et al. G3 (Bethesda). .

Abstract

We observed that current high-throughput sequencing approaches only detected a fraction of the full size-spectrum of insertions, deletions, and copy number variants compared with a previously published, Sanger-sequenced human genome. The sensitivity for detection was the lowest in the 100- to 10,000-bp size range, and at DNA repeats, with copy number gains harder to delineate than losses. We discuss strategies for discovering the full spectrum of genetic variation necessary for disease association studies.

Keywords: copy number variation; genome variation annotation; high-throughput sequencing; insertion/deletion.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Variation distribution of genomes sequenced. The size distribution of nonredundant (A) gains and (B) losses detected in the HuRef and 79 other samples. The proportion of nonredundant (C) gains and (D) losses detected in HuRef by CG in comparison with HuRef Standard.
Figure 2
Figure 2
Size distribution of HuRef CG gains and losses detected by each discovery strategy examined: split-read, paired-end mapping and read depth. (A) Gains. (B) Losses.
See this image and copyright information in PMC

References

    1. Drmanac R., Sparks A. B., Callow M. J., Halpern A. L., Burns N. L., et al. , 2010. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327: 78–81. - PubMed
    1. Gnerre S., Maccallum I., Przybylski D., Ribeiro F. J., Burton J. N., et al. , 2011. High-quality draft assemblies of mammalian genomes from massively parallel sequence data. Proc. Natl. Acad. Sci. USA 108: 1513–1518. - PMC - PubMed
    1. Hajirasouliha I., Hormozdiari F., Alkan C., Kidd J. M., Birol I., et al. , 2010. Detection and characterization of novel sequence insertions using paired-end next-generation sequencing. Bioinformatics 26: 1277–1283. - PMC - PubMed
    1. Khaja R., Zhang J., MacDonald J. R., He Y., Joseph-George A. M., et al. , 2006. Genome assembly comparison identifies structural variants in the human genome. Nat. Genet. 38: 1413–1418. - PMC - PubMed
    1. Lam E. T., Hastie A., Lin C., Ehrlich D., Das S. K., et al. , 2012a Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly. Nat. Biotechnol. 30: 771–776. - PMC - PubMed

Publication types

LinkOut - more resources