Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA)n Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?
Abstract
:1. Introduction
2. Results
2.1. Genotyping Results
2.2. Genotype Concordance between Illumina Sequencing, Fragment Analysis, and Fluorescent PCR
2.3. Genotype Concordance in Direct Sequencing, Gel Sizing, Pyrosequencing, DMET Plus, and Pharmacoscan
2.4. Phenotype Concordance
2.5. Comparisons with Previously Published Peer-Reviewed Data
3. Discussion
4. Materials and Methods
4.1. Patients and Samples
4.2. Illumina Sequencing (MiSeq)
4.3. Fragment Analysis
4.4. Direct Sequencing (in-House)
4.5. Pyrosequencing
4.6. DMET Plus
4.7. Statistical Considerations
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Star Nomenclature | (TA)n | Expression/Function * |
---|---|---|
UGT1A1*36 | 5 | Highest |
UGT1A1*1 | 6 | High |
UGT1A1*28 | 7 | Low |
UGT1A1*37 | 8 | Lowest |
*36/*36 | *36/*1 | *1/*1 | *36/*28 | *1/*28 | *1/*37 | *28/*28 | *28/*37 | Not Called | |
---|---|---|---|---|---|---|---|---|---|
Platform | n = (%) | n = (%) | n = (%) | n = (%) | n = (%) | n = (%) | n = (%) | n = (%) | n = (%) |
(TA)n/(TA)n | 5/5 | 5/6 | 6/6 | 5/6 | 6/7 | 6/8 | 7/7 | 7/8 | |
Metabolism Status | Normal | Intermediate | Poor | ||||||
Illumina (n = 163) | |||||||||
Female (n = 63) | 2 (3.2) | 24 (38.1) | 29 (46) | 1 (1.6) | 7 (11.1) | ||||
Male (n = 100) | 46 (46) | 6 (6) | 34 (34) | 13 (13) | 1 (1) | ||||
Caucasian (non-Hispanic) (n = 105) | 56 (49.1) | 48 (42.1) | 10 (8.8) | ||||||
Black or African American (n = 32) | 1 (3.1) | 7 (21.9) | 6 (18.8) | 8 (25) | 1 (3.1) | 8 (25) | 1 (3.1) | ||
Hispanic or Latino (n = 5) | 1 (20) | 2 (40) | 2 (40) | ||||||
Asian or Pacific Islander (n = 9) | 5 (55.6) | 4 (44.4) | |||||||
Other or Unknown (n = 3) | 1 (33.3) | 2 (66.7) | |||||||
Fragment Analysis (n = 163) | |||||||||
Female (n = 63) | 2 (3.2) | 24 (38.1) | 29 (46) | 1 (1.6) | 7 (11.1) | ||||
Male (n = 100) | 46 (46) | 6 (6) | 34 (34) | 13 (13) | 1 (1) | ||||
Caucasian (non-Hispanic) (n = 105) | 56 (49.1) | 48 (42.1) | 10 (8.8) | ||||||
Black or African American (n = 32) | 1 (3.1) | 7 (21.9) | 6 (18.8) | 8 (25) | 1 (3.1) | 8 (25) | 1 (3.1) | ||
Hispanic or Latino (n = 5) | 1 (20) | 2 (40) | 2 (40) | ||||||
Asian or Pacific Islander (n = 9) | 5 (55.6) | 4 (44.4) | |||||||
Other or Unknown (n = 3) | 1 (33.3) | 2 (66.7) | |||||||
fPCR (n = 9) 1 | |||||||||
Female (n = 6) | 2 (33.3) | 1 (16.7) | 1 (16.7) | 1 (16.7) | 1 (16.7) | ||||
Male (n = 7) | 1 (14.3) | 2 (28.6) | 2 (28.6) | 1 (14.3) | 1 (14.3) | ||||
Caucasian (non-Hispanic) (n = 6) | 2 (33.3) | 2 (33.3) | 2 (33.3) | ||||||
Black or African American (n = 6) | 1 (16.7) | 2 (33.3) | 1 (16.7) | 1 (16.7) | 1 (16.7) | ||||
Hispanic or Latino (n = 1) | 1 (100) | ||||||||
Pyrosequencing (n = 162) | |||||||||
Female (n = 63) | 2 (3.2) | 23 (36.5) | 29 (46) | 6 (9.5) | 3 (4.8) | ||||
Male (n = 99) | 45 (45.5) | 5 (5.1) | 32 (32.3) | 13 (13.1) | 4 (4) | ||||
Caucasian (non-Hispanic) (n = 113) | 54 (47.8) | 47 (41.6) | 9 (8) | 3 (2.7) | |||||
Black or African American (n = 32) | 1 (3.1) | 7 (21.9) | 5 (15.6) | 7 (21.9) | 8 (25) | 4 (12.5) | |||
Hispanic or Latino (n = 5) | 1 (20) | 2 (40) | 2 (40) | ||||||
Asian or Pacific Islander (n = 9) | 5 (55.6) | 4 (44.4) | |||||||
Other or Unknown (n = 3) | 1 (33.3) | 2 (66.7) | |||||||
Pyromark Gel (n = 162) | |||||||||
Female (n = 63) | 2 (3.2) | 24 (38.1) | 29 (46) | 7 (11.1) | 1 (1.6) | ||||
Male (n = 99) | 46 (46.5) | 5 (5.1) | 33 (33.3) | 13 (13.1) | 2 (2) | ||||
Caucasian (non-Hispanic) (n = 113) | 56 (49.6) | 47 (41.6) | 10 (8.8) | ||||||
Black or African American (n = 32) | 1 (3.1) | 7 (21.9) | 5 (15.6) | 8 (25) | 8 (25) | 3 (9.4) | |||
Hispanic or Latino (n = 5) | 1 (20) | 2 (40) | 2 (40) | ||||||
Asian or Pacific Islander (n = 9) | 5 (55.6) | 4 (44.4) | |||||||
Other or Unknown (n = 3) | 1 (33.3) | 2 (66.7) | |||||||
DMET (n = 168) 2 | |||||||||
Female (n = 65) | 28 (43.1) | 30 (46.2) | 7 (10.8) | ||||||
Male (n = 103) | 55 (53.4) | 34 (33) | 14 (13.6) | ||||||
Caucasian (non-Hispanic) (n = 117) | 60 (51.3) | 47 (40.2) | 10 (8.5) | ||||||
Black or African American (n = 32) | 13 (40.6) | 10 (31.3) | 9 (28.1) | ||||||
Hispanic or Latino (n = 5) | 3 (60) | 2 (40) | |||||||
Asian or Pacific Islander (n = 11) | 7 (63.6) | 4 (36.4) | |||||||
Other or Unknown (n = 3) | 1 (33.3) | 2 (66.7) | |||||||
Pharmacoscan (n = 21) 1,3 | |||||||||
Female (n = 5) | 1 (20) | 2 (40) | 1 (20) | 1 (20) | |||||
Male (n = 16) | 2 (12.5) | 5 (31.3) | 6 (37.5) | 3 (18.8) | |||||
Caucasian (non-Hispanic) (n = 11) | 3 (27.3) | 5 (45.5) | 3 (27.3) | ||||||
Black or African American (n = 9) | 1 (11.1) | 5 (55.6) | 2 (22.2) | 1 (11.1) | |||||
Hispanic or Latino (n = 1) | 1 (100) |
Illumina Fraction (%) | Fragment Analysis Fraction (%) | DMET Plus Fraction (%) | Pyrosequencing Fraction (%) | |
---|---|---|---|---|
Miscalls only | ||||
Illumina (n = 163) | x | 163/163 (100) | 154/163 (94.5) | 155/155 (100) |
Fragment Analysis (n = 163) | x | 154/163 (94.5) | 155/155 (100) | |
DMET Plus (n = 168) | x | 146/155 (94.2) | ||
Pyrosequencing (n = 155) * | x | |||
Miscalls and ambiguous calls | ||||
Illumina (n = 163) | x | 163/163 (100) | 159/163 (97.5) | 155/162 (95.7) |
Fragment Analysis (n = 163) | x | 159/163 (97.5) | 155/162 (95.7) | |
DMET Plus (n = 168) | x | 146/162 (90.1) | ||
Pyrosequencing (n = 162) * | x |
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Sissung, T.M.; Barbier, R.H.; Price, D.K.; Plona, T.M.; Pike, K.M.; Mellott, S.D.; Baugher, R.N.; Whiteley, G.R.; Soppet, D.R.; Venzon, D.; et al. Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA)n Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors? Int. J. Mol. Sci. 2020, 21, 896. https://doi.org/10.3390/ijms21030896
Sissung TM, Barbier RH, Price DK, Plona TM, Pike KM, Mellott SD, Baugher RN, Whiteley GR, Soppet DR, Venzon D, et al. Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA)n Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors? International Journal of Molecular Sciences. 2020; 21(3):896. https://doi.org/10.3390/ijms21030896
Chicago/Turabian StyleSissung, Tristan M., Roberto H. Barbier, Douglas K. Price, Teri M. Plona, Kristen M. Pike, Stephanie D. Mellott, Ryan N. Baugher, Gordon R. Whiteley, Daniel R. Soppet, David Venzon, and et al. 2020. "Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA)n Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?" International Journal of Molecular Sciences 21, no. 3: 896. https://doi.org/10.3390/ijms21030896