TY - JOUR
T1 - Development of a fingerprinting panel using medically relevant polymorphisms
AU - Cross, Deanna S.
AU - Ivacic, Lynn C.
AU - McCarty, Catherine A.
N1 - Funding Information:
This study was supported by grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health The authors would like to acknowledge the Genetics Core Laboratory of the Marshfield Clinic Research Foundation, Elisha Bergmann, Sherri Reisner, and Valerie Roehrs for their sample handling, preparation, and support. In addition we would like to thank Yvonne Cerne for her graphics support.
PY - 2009
Y1 - 2009
N2 - Background. For population based biorepositories to be of use, rigorous quality control and assurance must be maintained. We have designed and validated a panel of polymorphisms for individual sample identification consisting of 36 common polymorphisms that have been implicated in a wide range of diseases and an additional sex marker. This panel uniquely identifies our biorepository of approximately 20,000 samples and would continue to uniquely identify samples in biorepositories of over 100 million samples. Methods. A panel of polymorphisms associated with at least one disease state in multiple populations was constructed using a cut-off of 0.20 or greater confirmed minor allele frequency in a European Caucasian population. The fingerprinting assay was tested using the MALDI-TOF mass spectrometry method of allele determination on a Sequenom platform with a panel of 28 Caucasian HapMap samples; the results were compared with known genotypes to ensure accuracy. The frequencies of the alleles were compared to the expected frequencies from dbSNP and any genotype that did not achieve Hardy Weinberg equilibrium was excluded from the final assay. Results. The final assay consisted of the AMG sex marker and 36 medically relevant polymorphisms with representation on each chromosome, encompassing polymorphisms on both the Illumina 550K bead array and the Affymetrix 6.0 chip (with over a million polymorphisms) platform. The validated assay has a P(ID) of 6.132 × 10-15and a Psib(ID) of 3.077 × 10-8. This assay allows unique identification of our biorepository of 20,000 individuals as well and ensures that as we continue to recruit individuals they can be uniquely fingerprinted. In addition, diseases such as cancer, heart disease diabetes, obesity, and respiratory disease are well represented in the fingerprinting assay. Conclusion. The polymorphisms in this panel are currently represented on a number of common genotyping platforms making QA/QC flexible enough to accommodate a large number of studies. In addition, this panel can serve as a resource for investigators who are interested in the effects of disease in a population, particularly for common diseases.
AB - Background. For population based biorepositories to be of use, rigorous quality control and assurance must be maintained. We have designed and validated a panel of polymorphisms for individual sample identification consisting of 36 common polymorphisms that have been implicated in a wide range of diseases and an additional sex marker. This panel uniquely identifies our biorepository of approximately 20,000 samples and would continue to uniquely identify samples in biorepositories of over 100 million samples. Methods. A panel of polymorphisms associated with at least one disease state in multiple populations was constructed using a cut-off of 0.20 or greater confirmed minor allele frequency in a European Caucasian population. The fingerprinting assay was tested using the MALDI-TOF mass spectrometry method of allele determination on a Sequenom platform with a panel of 28 Caucasian HapMap samples; the results were compared with known genotypes to ensure accuracy. The frequencies of the alleles were compared to the expected frequencies from dbSNP and any genotype that did not achieve Hardy Weinberg equilibrium was excluded from the final assay. Results. The final assay consisted of the AMG sex marker and 36 medically relevant polymorphisms with representation on each chromosome, encompassing polymorphisms on both the Illumina 550K bead array and the Affymetrix 6.0 chip (with over a million polymorphisms) platform. The validated assay has a P(ID) of 6.132 × 10-15and a Psib(ID) of 3.077 × 10-8. This assay allows unique identification of our biorepository of 20,000 individuals as well and ensures that as we continue to recruit individuals they can be uniquely fingerprinted. In addition, diseases such as cancer, heart disease diabetes, obesity, and respiratory disease are well represented in the fingerprinting assay. Conclusion. The polymorphisms in this panel are currently represented on a number of common genotyping platforms making QA/QC flexible enough to accommodate a large number of studies. In addition, this panel can serve as a resource for investigators who are interested in the effects of disease in a population, particularly for common diseases.
UR - http://www.scopus.com/inward/record.url?scp=66249147911&partnerID=8YFLogxK
U2 - 10.1186/1755-8794-2-17
DO - 10.1186/1755-8794-2-17
M3 - Article
C2 - 19379518
AN - SCOPUS:66249147911
SN - 1755-8794
VL - 2
JO - BMC Medical Genomics
JF - BMC Medical Genomics
M1 - 17
ER -