An exceedingly exclusive club recently welcomed two new members, with the publication of the complete genome sequences of an African and a Chinese man in the November 6 issue of Nature. That brings to four the number of people who have had their personal genetic code read in its entirety. James Watson, co-discoverer of the double helix, and sequencing pioneer Craig Venter were the first two. Now, they are joined by a pair of anonymous individuals, as a group led by David Bentley of Illumina Cambridge Ltd. in Essex, UK, reports the complete genome of a Nigerian man, while Jun Wang, Jian Wang and colleagues from Shenzhen University, China, release the genetic makeup of a Han Chinese man. No women in the club as of yet.
The new genomes were accomplished in a fraction of the time and cost of the Watson and Venter efforts, and the accomplishment moves researchers one step closer to the goal of routine personal genome sequencing for medical and research purposes.
Both groups used massively parallel chip-based sequencing techniques that can produce 100 million short 35 base-pair sequences at one time. Using multiple chips, the groups generated between 4 and 17 billion bases worth of sequence data per week (the complete human genome has about three billion bases). The short reads were assembled using the existing reference genome as a template. In eight weeks, at a cost of $250,000 for reagents, the Bentley team produced 135 billion bases of sequence, an average 40-fold coverage of the genome. The Wang team had comparable output at a price they put at less than $500,000. For comparison, Watson’s genome cost $10 million to complete, at 7.5-fold coverage.
Because of the high coverage rate, the sequences were highly accurate. For example, 99 percent of the roughly 3 million known single nucleotide polymorphisms (SNPs) were confirmed, and an additional million more SNPs were identified. The incidence of insertions and deletions was similar to that seen with the previous work, although the technique preferentially detected deletions and small insertions.
“The approach of Bentley, Wang and their colleagues represents a substantial advance in the sequencing of individual genomes,” write Samuel Levy and Robert Strausberg of the J. Craig Venter Institute of Rockville, Maryland, in an accompanying commentary. “They reinforce the catalog of variants that exist in human genomes—SNPs in the millions, insertion/deletion polymorphisms in the hundreds of thousands and structural variants in the thousands.”
Interestingly, the Chinese man appears to have an elevated risk for Alzheimer disease based on his APOE and SORL1 alleles, but there is no family information available that might indicate a history of AD. Assigning risk using known genes is one important application of personal genomics. Another is using genotype-phenotype associations to uncover genes and variants associated with disease, an effort that will depend on having many more individual genomes. With both the Chinese and British groups participating in the 1000 Genomes Project, the "completely sequenced" club might be looking at a major boost in membership soon.—Pat McCaffrey
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- Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IM, Reed MT, Rigatti R, Rodighiero C, Ross MT, Sabot A, Sankar SV, Scally A, Schroth GP, Smith ME, Smith VP, Spiridou A, Torrance PE, Tzonev SS, Vermaas EH, Walter K, Wu X, Zhang L, Alam MD, Anastasi C, Aniebo IC, Bailey DM, Bancarz IR, Banerjee S, Barbour SG, Baybayan PA, Benoit VA, Benson KF, Bevis C, Black PJ, Boodhun A, Brennan JS, Bridgham JA, Brown RC, Brown AA, Buermann DH, Bundu AA, Burrows JC, Carter NP, Castillo N, Chiara E Catenazzi M, Chang S, Neil Cooley R, Crake NR, Dada OO, Diakoumakos KD, Dominguez-Fernandez B, Earnshaw DJ, Egbujor UC, Elmore DW, Etchin SS, Ewan MR, Fedurco M, Fraser LJ, Fuentes Fajardo KV, Scott Furey W, George D, Gietzen KJ, Goddard CP, Golda GS, Granieri PA, Green DE, Gustafson DL, Hansen NF, Harnish K, Haudenschild CD, Heyer NI, Hims MM, Ho JT, Horgan AM, Hoschler K, Hurwitz S, Ivanov DV, Johnson MQ, James T, Huw Jones TA, Kang GD, Kerelska TH, Kersey AD, Khrebtukova I, Kindwall AP, Kingsbury Z, Kokko-Gonzales PI, Kumar A, Laurent MA, Lawley CT, Lee SE, Lee X, Liao AK, Loch JA, Lok M, Luo S, Mammen RM, Martin JW, McCauley PG, McNitt P, Mehta P, Moon KW, Mullens JW, Newington T, Ning Z, Ling Ng B, Novo SM, O'Neill MJ, Osborne MA, Osnowski A, Ostadan O, Paraschos LL, Pickering L, Pike AC, Chris Pinkard D, Pliskin DP, Podhasky J, Quijano VJ, Raczy C, Rae VH, Rawlings SR, Chiva Rodriguez A, Roe PM, Rogers J, Rogert Bacigalupo MC, Romanov N, Romieu A, Roth RK, Rourke NJ, Ruediger ST, Rusman E, Sanches-Kuiper RM, Schenker MR, Seoane JM, Shaw RJ, Shiver MK, Short SW, Sizto NL, Sluis JP, Smith MA, Ernest Sohna Sohna J, Spence EJ, Stevens K, Sutton N, Szajkowski L, Tregidgo CL, Turcatti G, Vandevondele S, Verhovsky Y, Virk SM, Wakelin S, Walcott GC, Wang J, Worsley GJ, Yan J, Yau L, Zuerlein M, Mullikin JC, Hurles ME, McCooke NJ, West JS, Oaks FL, Lundberg PL, Klenerman D, Durbin R, Smith AJ. Accurate whole human genome sequencing using reversible terminator chemistry. Nature. 2008 Nov 6;456(7218):53-9. PubMed.
- Wang J, Wang W, Li R, Li Y, Tian G, Goodman L, Fan W, Zhang J, Li J, Guo Y, Feng B, Li H, Lu Y, Fang X, Liang H, Du Z, Li D, Zhao Y, Hu Y, Yang Z, Zheng H, Hellmann I, Inouye M, Pool J, Yi X, Zhao J, Duan J, Zhou Y, Qin J, Ma L, Li G, Zhang G, Yang B, Yu C, Liang F, Li W, Li S, Ni P, Ruan J, Li Q, Zhu H, Liu D, Lu Z, Li N, Guo G, Ye J, Fang L, Hao Q, Chen Q, Liang Y, Su Y, San A, Ping C, Yang S, Chen F, Li L, Zhou K, Ren Y, Yang L, Gao Y, Yang G, Li Z, Feng X, Kristiansen K, Wong GK, Nielsen R, Durbin R, Bolund L, Zhang X, Yang H. The diploid genome sequence of an Asian individual. Nature. 2008 Nov 6;456(7218):60-5. PubMed.
- Levy S, Strausberg RL. Human genetics: Individual genomes diversify. Nature. 2008 Nov 6;456(7218):49-51. PubMed.