The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants.

Reuter MS1, Walker S1, Thiruvahindrapuram B1, Whitney J1, Cohn I1, Sondheimer N1, Yuen RKC1, Trost B1, Paton TA1, Pereira SL1, Herbrick JA1, Wintle RF1, Merico D1, Howe J1, MacDonald JR1, Lu C1, Nalpathamkalam T1, Sung WWL1, Wang Z1, Patel RV1, Pellecchia G1, Wei J1, Strug LJ1, Bell S1, Kellam B1, Mahtani MM1, Bassett AS1, Bombard Y1, Weksberg R1, Shuman C1, Cohn RD1, Stavropoulos DJ1, Bowdin S1, Hildebrandt MR1, Wei W1, Romm A1, Pasceri P1, Ellis J1, Ray P1, Meyn MS1, Monfared N1, Hosseini SM1, Joseph-George AM1, Keeley FW1, Cook RA1, Fiume M1, Lee HC1, Marshall CR1, Davies J1, Hazell A1, Buchanan JA1, Szego MJ1, Scherer SW2.

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Abstract

BACKGROUND:

The Personal Genome Project Canada is a comprehensive public data resource that integrates whole genome sequencing data and health information. We describe genomic variation identified in the initial recruitment cohort of 56 volunteers.

METHODS:

Volunteers were screened for eligibility and provided informed consent for open data sharing. Using blood DNA, we performed whole genome sequencing and identified all possible classes of DNA variants. A genetic counsellor explained the implication of the results to each participant.

RESULTS:

Whole genome sequencing of the first 56 participants identified 207 662 805 sequence variants and 27 494 copy number variations. We analyzed a prioritized disease-associated data set (n = 1606 variants) according to standardized guidelines, and interpreted 19 variants in 14 participants (25%) as having obvious health implications. Six of these variants (e.g., in BRCA1 or mosaic loss of an X chromosome) were pathogenic or likely pathogenic. Seven were risk factors for cancer, cardiovascular or neurobehavioural conditions. Four other variants - associated with cancer, cardiac or neurodegenerative phenotypes - remained of uncertain significance because of discrepancies among databases. We also identified a large structural chromosome aberration and a likely pathogenic mitochondrial variant. There were 172 recessive disease alleles (e.g., 5 individuals carried mutations for cystic fibrosis). Pharmacogenomics analyses revealed another 3.9 potentially relevant genotypes per individual.

INTERPRETATION:

Our analyses identified a spectrum of genetic variants with potential health impact in 25% of participants. When also considering recessive alleles and variants with potential pharmacologic relevance, all 56 participants had medically relevant findings. Although access is mostly limited to research, whole genome sequencing can provide specific and novel information with the potential of major impact for health care.