Realities and Limitations of Coverage in Current "Whole''-Exome Sequencing Capture Approaches

Kevin Jacobs, Meredith Yeager, Michael Cullen, Xijun Zhang, Joseph Boland, Jennifer Bacior, Victor Lonsberry, Casey Matthews, David Roberson, Quan Chen, Laurie Burdett, Idan Menashe, Xiaohong Yang, Lynn Goldin, Mary McMaster, Neil Caporaso, Philip Taylor, Maria Landi, Joshua Sampson, Alisa Goldstein

Research output: Contribution to journalMeeting Abstract


New technologies such as ‘‘whole’’-exome sequencingcapture methods have led to renewed excitement aboutdiscovering more rare, Mendelian, high-risk susceptibilitygene variants in humans. To assess ‘‘whole’’-exomesequence capture approaches with respect to coverage,we evaluated the content and the empirical performance ofthe currently available ‘‘whole’’-exome sequence capturemethods [NimbleGen Sequence Capture 2.1 M HumanExome Array; Agilent SureSelect Human All Exon Kit] onthree sequencing platforms [454 FLX Ti (4 runs); ABISOLiD (1 quadrant); Illumina GA II (2 lanes)]. The proteincoding sequences (CDS) reported in the RefSeq database(build 36.3) served as the gold standard. NimbleGencapture probes currently target 77% of CDS bases andAgilent capture probes target 83% of CDS bases. Weobserved 21.5 Mbps (65%), 25.0 Mbps (76%) and 23.4 Mbps(71%) of the 33.0 Mbps of CDS with ?8x sequence depth forNimblegen/454, Agilent/SOLiD, and Agilent/Illumina,respectively. Since identification of rare gene variantsrequires high per-gene coverage, we also computed theproportion of genes with 490% of CDS bases covered with?8X sequence depth. Only 42%, 55%, and 45% of geneswere covered by Nimblegen/454, Agilent/SOLiD, andAgilent/Illumina, respectively. Coverage of entire geneCDS is presently incomplete, thus negative results must beinterpreted cautiously since it is not currently possible tofully exclude most genes from consideration of harboringcausal mutations.
Original languageEnglish
Pages (from-to)919-920
Number of pages2
JournalGenetic Epidemiology
StatePublished - 22 Nov 2010


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