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A new DNA-sequencing method allows researchers to efficiently determine haplotypes—sequence variants that are usually inherited together—using an amount of DNA equivalent to the amount from only 10 to 20 cells. The method was developed by a team led by Brock A. Peters and Radoje Drmanac of Complete Genomics, a Mountain View, Calif., sequencing firm (Nature, DOI: 10.1038/nature11236). The ability to determine haplotypes is clinically important for identifying whether mutations occur in one or both copies of a gene. In Complete Genomics’ “long fragment read” approach, about 100 pg of 100-kilobase DNA is physically separated into 384 pools, with each pool containing 10 to 20% of one copy of the genome. The DNA is amplified, fragmented, and labeled with a DNA bar code that identifies the well. The fragments are then combined, amplified again (including the bar codes), and then sequenced. The bar codes allow sequences to be mapped back to the original fragment they came from. To test the method, the researchers determined haplotypes of samples from the International HapMap Project and found that they were able to accurately assign up to 97% of single-nucleotide polymorphisms to correct haplotypes. The error rate was 1 in 10 megabases, they report.
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