The Broad Institute of Harvard and MIT SPARC funding for a portion of the Personal Genome Project (PGP)

This portion of the PGP has two main aims:

(1) Technical. To improve methods for selective capture of genomic regions (initially exons) and to improve the cost and accuracy of polony sequencing.
   The reliable capture of specific genomic regions would be extremely valuable for a wide range of applications in medical genetics. It would make it possible to focus sequencing on (say) 1% of a genome - thereby increasing the efficiency of sequencing by up to 100-fold. This would have enormous implications for studies of both inherited and somatic genetics.

(2) Biological. To explore the ability to interpret observed sequence differences, in the context of a novel IRB-approved consent protocol that permits the investigators to link genotype and phenotype and to re-approach the subjects to obtain additional phenotypic information.
   It will soon be possible to perform genome-scale sequencing on large collections of individuals. Such data will raise thousands questions of the form: Does an observed common or rare sequence variation (e.g., a stop codon frame-shift, missense mutation, or change to conserved regulatory region) in a gene have any phenotypic consequence? Does it correlate with a known phenotype that has already ascertained? Does it suggest a link with new phenotype that should be tested in some of the individuals (perhaps by a biochemical or physiological challenge)?
   This study will provide an early opportunity to explore both the important scientific and patient-oriented issues that will arise in such work, in the context of a novel IRB-approved protocol designed for this purpose. In addition, while the study size is too small to establish statistically significant correlations between genotype and phentoype, it may generate testable hypotheses about specific traits. Phenotypes collected on patients will focus on medically relevant traits, as well as objective physical descriptors (e.g., eye-color, hair-color).