TY - JOUR
T1 - High-depth whole genome sequencing of an Ashkenazi Jewish reference panel
T2 - enhancing sensitivity, accuracy, and imputation
AU - Lencz, Todd
AU - Yu, Jin
AU - Palmer, Cameron
AU - Carmi, Shai
AU - Ben-Avraham, Danny
AU - Barzilai, Nir
AU - Bressman, Susan
AU - Darvasi, Ariel
AU - Cho, Judy H.
AU - Clark, Lorraine N.
AU - Gümüş, Zeynep H.
AU - Joseph, Vijai
AU - Klein, Robert
AU - Lipkin, Steven
AU - Offit, Kenneth
AU - Ostrer, Harry
AU - Ozelius, Laurie J.
AU - Peter, Inga
AU - Atzmon, Gil
AU - Pe’er, Itsik
N1 - Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - While increasingly large reference panels for genome-wide imputation have been recently made available, the degree to which imputation accuracy can be enhanced by population-specific reference panels remains an open question. Here, we sequenced at full-depth (≥ 30×), across two platforms (Illumina X Ten and Complete Genomics, Inc.), a moderately large (n = 738) cohort of samples drawn from the Ashkenazi Jewish population. We developed a series of quality control steps to optimize sensitivity, specificity, and comprehensiveness of variant calls in the reference panel, and then tested the accuracy of imputation against target cohorts drawn from the same population. Quality control (QC) thresholds for the Illumina X Ten platform were identified that permitted highly accurate calling of single nucleotide variants across 94% of the genome. QC procedures also identified numerous regions that are poorly mapped using current reference or alternate assemblies. After stringent QC, the population-specific reference panel produced more accurate and comprehensive imputation results relative to publicly available, large cosmopolitan reference panels, especially in the range of rare variants that may be most critical to further progress in mapping of complex phenotypes. The population-specific reference panel also permitted enhanced filtering of clinically irrelevant variants from personal genomes.
AB - While increasingly large reference panels for genome-wide imputation have been recently made available, the degree to which imputation accuracy can be enhanced by population-specific reference panels remains an open question. Here, we sequenced at full-depth (≥ 30×), across two platforms (Illumina X Ten and Complete Genomics, Inc.), a moderately large (n = 738) cohort of samples drawn from the Ashkenazi Jewish population. We developed a series of quality control steps to optimize sensitivity, specificity, and comprehensiveness of variant calls in the reference panel, and then tested the accuracy of imputation against target cohorts drawn from the same population. Quality control (QC) thresholds for the Illumina X Ten platform were identified that permitted highly accurate calling of single nucleotide variants across 94% of the genome. QC procedures also identified numerous regions that are poorly mapped using current reference or alternate assemblies. After stringent QC, the population-specific reference panel produced more accurate and comprehensive imputation results relative to publicly available, large cosmopolitan reference panels, especially in the range of rare variants that may be most critical to further progress in mapping of complex phenotypes. The population-specific reference panel also permitted enhanced filtering of clinically irrelevant variants from personal genomes.
UR - http://www.scopus.com/inward/record.url?scp=85046024891&partnerID=8YFLogxK
U2 - 10.1007/s00439-018-1886-z
DO - 10.1007/s00439-018-1886-z
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 29705978
AN - SCOPUS:85046024891
SN - 0340-6717
VL - 137
SP - 343
EP - 355
JO - Human Genetics
JF - Human Genetics
IS - 4
ER -