Tuesday, 20 September 2011

Stanford-Led Team Demonstrates Utility of Ethnicity-Specific Reference for Interpreting Genome Data

excerpted from Genomeweb

NEW YORK (GenomeWeb News) – In a study appearing online last night in PLoS Genetics, a Stanford University-led team described the "ethnicity-specific" reference genome approach it used to analyze whole genome sequences from four members of a single family.

By incorporating estimated allele frequency data from the 1000 Genomes Project into the existing human reference genome, the researchers came up with three synthetic human genome references containing the major alleles identified in European, African, or East Asian populations — a strategy that's intended to more accurately represent the genetic variation present in each of the major HapMap populations.

Whole-genome sequencing and clinical annotation

  • Construction of and alignment to an ethnicity-specific major allele reference sequence yielded improved alignment and more accurate genotyping, especially at disease-associated loci.
  • Mendelian inheritance state analysis in the family structure enabled identification and removal of >90% of variants arising from sequencing errors.
  • Per-trio phasing, inheritance state of adjacent variants, and population-level linkage disequilibrium data were integrated to provide long-range phased haplotypes.
  • By fine-mapping recombination events to sub-kilobase resolution, the authors were able to perform sequence-based human lymphocyte antigen (HLA) typing.
  • A curated database of genotype-phenotype correlations made it possible to construct comprehensive genetic risk profiles, including multigenic risk of inherited thrombophilia, common disease susceptibility, and pharmacogenomics.

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