Online citations, reference lists, and bibliographies.
← Back to Search

High Throughput Parallel Analysis Of Hundreds Of Patient Samples For More Than 100 Mutations In Multiple Disease Genes.

A. P. Shuber, L. A. Michalowsky, G. Nass, J. Skoletsky, L. M. Hire, S. Kotsopoulos, M. Phipps, D. Barberio, K. Klinger
Published 1997 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.
This paper references
10.1038/NG0693-202
A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews
Michael A. Whitney (1993)
10.1073/PNAS.86.16.6230
Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes.
R. Saiki (1989)
10.1016/0888-7543(92)90014-J
Analyzing and comparing nucleic acid sequences by hybridization to arrays of oligonucleotides: evaluation using experimental models.
E. Southern (1992)
Structure of human hemoglobin messenger RNA and its relation to hemoglobinopathies.
J. Wilson (1977)
The major defect in Ashkenazi Jews with Tay-Sachs disease is an insertion in the gene for the alpha-chain of beta-hexosaminidase.
R. Myerowitz (1988)
10.1016/0888-7543(89)90290-5
Sequencing of megabase plus DNA by hybridization: theory of the method.
R. Drmanac (1989)
Isolation of a strong candidate for the 17q-linked breast and ovarian cancer susceptibility gene
K Norris (1994)
10.1093/NAR/17.7.2503
Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS).
C. Newton (1989)
10.1038/313495A0
Detection of single base substitutions in total genomic DNA
R. Myers (1985)
10.1093/NAR/13.4.1173
Solid-phase methods for sequencing of nucleic acids I. Simultaneous sequencing of different oligodeoxyribonucleotides using a new, mechanically stable anion-exchange paper.
A. Rosenthal (1985)
10.1016/0888-7543(91)90503-7
Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
J. Zieleński (1991)
10.1073/PNAS.91.11.5022
Light-generated oligonucleotide arrays for rapid DNA sequence analysis.
A. C. Pease (1994)
10.1016/0888-7543(89)90319-4
The human glucocerebrosidase gene and pseudogene: structure and evolution.
M. Horowitz (1989)
10.1038/379749A0
Identification of the breast cancer susceptibility gene BRCA2
R. Wooster (1996)
10.1038/NG0895-375
How to find all those mutations
S. Forrest (1995)
10.1126/SCIENCE.4071043
Detection of single base substitutions by ribonuclease cleavage at mismatches in RNA:DNA duplexes.
R. Myers (1985)
10.1073/PNAS.86.8.2766
Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms.
M. Orita (1989)
10.1016/0027-5107(93)90060-S
Current methods of mutation detection.
R. Cotton (1993)
10.1093/NAR/22.24.5456
Direct fluorescence analysis of genetic polymorphisms by hybridization with oligonucleotide arrays on glass supports.
Z. Guo (1994)
10.1126/SCIENCE.3413476
A ligase-mediated gene detection technique.
U. Landegren (1988)
10.1038/334119A0
A point mutation in the last intron responsible for increased expression and transforming activity of the c-Ha-ras oncogene
J. Cohen (1988)
10.1073/PNAS.85.12.4397
Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.
R. Cotton (1988)
10.1101/GR.5.5.488
A simplified procedure for developing multiplex PCRs.
A. P. Shuber (1995)
10.1038/NG1093-118
Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease
R. Kaul (1993)
10.1016/0168-9525(91)90004-A
Rapid detection of single base mismatches as heteroduplexes on Hydrolink gels.
J. Keen (1991)
10.1093/NAR/18.12.3671
Primer extension technique for the detection of single nucleotide in genomic DNA.
B. P. Sokolov (1990)
10.1016/0165-1218(93)90130-6
Analyses of cytogenetic damage in rodents following exposure to simulated groundwater contaminated with pesticides and a fertilizer.
A. Kligerman (1993)
10.1073/PNAS.82.6.1585
Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries.
W. Wood (1985)
10.1093/NAR/9.4.879
The use of synthetic oligonucleotides as hybridization probes. II. Hybridization of oligonucleotides of mixed sequence to rabbit beta-globin DNA.
R. Wallace (1981)
10.1016/0014-5793(89)81730-2
An oligonucleotide hybridization approach to DNA sequencing
K. R. Khrapko (1989)
10.1126/SCIENCE.7545954
A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
Y. Miki (1994)
10.1016/S0022-5193(88)80246-7
A novel method for nucleic acid sequence determination.
W. Bains (1988)
10.1038/378789A0
Identification of the breast cancer susceptibility gene BRCA2
R. Wooster (1995)
10.1073/pnas.74.12.5463
DNA sequencing with chain-terminating inhibitors.
F. Sanger (1977)
Isolation of a strong candidate for the 17q-linked breast and ovarian cancer susceptibility gene, BRCA1
Y. Miki (1994)
10.1016/0092-8674(90)90186-I
A genetic model for colorectal tumorigenesis
E. Fearon (1990)
10.1093/HMG/2.2.153
Efficient 12-mutation testing in the CFTR gene: a general model for complex mutation analysis.
A. P. Shuber (1993)



This paper is referenced by
10.1016/S0958-1669(97)80117-6
Will genetics really revolutionize the drug discovery process?
L. M. Gelbert (1997)
10.1002/ijc.10273
Identification of BRCA1 and BRCA2 carriers by allele‐specific gene expression (AGE) analysis
M. Montagna (2002)
10.1016/S0003-2697(02)00019-2
Single-nucleotide polymorphism analysis by hybridization protection assay on solid support.
Susumu Goto (2002)
10.1136/JMG.35.6.443
"Code of practice and guidance on human genetic testing services supplied direct to the public". Advisory Committee on Genetic Testing.
J. C. Barber (1998)
10.1002/1522-2683()22:6<1024::AID-ELPS1024>3.0.CO;2-U
A commented dictionary of techniques for genotyping
J. Drabek (2001)
10.1093/BJA/AEH200
Principles of pharmacogenetics--implications for the anaesthetist.
G. Iohom (2004)
10.1016/S1050-3862(98)00014-X
Rolling circle amplification of DNA immobilized on solid surfaces and its application to multiplex mutation detection.
A. Hatch (1999)
SNP Technology and Alzheimers disease
W. M. Howell (2003)
10.3929/ETHZ-A-004363491
Establishment of quick-methods to reveal DNA-polymorphisms: single strand conformational polymorphism (SSCP) and heteroduplex analysis (HA)
S. Genini (2002)
10.1007/s000180050501
Current applications of single-cell PCR
S. Hahn (2000)
10.1002/anie.200801998
Ultrasensitive DNA detection using photonic crystals.
Mingzhu Li (2008)
10.1002/(SICI)1522-2683(19990101)20:6<1250::AID-ELPS1250>3.0.CO;2-5
Microplate array diagonal gel electrophoresis for mutation research in DNA banks
I. Day (1999)
10.1002/(SICI)1098-1004(1998)11:5<404::AID-HUMU8>3.0.CO;2-S
Rapid, efficient method for multiplex amplification from filter paper
M. Caggana (1998)
10.1007/3-540-26553-8_3
Systematischer Vergleich der Testverfahren
Henriette Schleberger (2005)
10.1016/S0197-1859(00)88685-9
Detection of point mutations on a DNA microchip
Timothy G. Hammond (1999)
10.1039/c1lc20126c
Multiplex digital PCR: breaking the one target per color barrier of quantitative PCR.
Qun Zhong (2011)
10.1002/0471142905.hg0904s41
Simultaneous Detection of Multiple Point Mutations Using Allele‐Specific Oligonucleotides
Nichole M Napolitano (2004)
10.1002/HUMU.1131
Automation in genotyping of single nucleotide polymorphisms
I. Gut (2001)
10.1016/S0272-2712(03)00033-7
Prenatal screening for cystic fibrosis.
C. Richards (2003)
10.1101/GR.8.8.769
Reading bits of genetic information: methods for single-nucleotide polymorphism analysis.
U. Landegren (1998)
10.2144/99273RR02
High-throughput single nucleotide polymorphism genotyping by fluorescent 5' exonuclease assay.
P. Morin (1999)
10.1016/s1567-7192(04)80013-5
Pharmacogenomics: Methodologies for genotyping and phenotyping
P. Jannetto (2004)
10.1023/A:1016110724564
DNA Aptamers as Radically New Recognition Elements for Biosensors
V. Spiridonova (2004)
Linkage Disequilibrium Analysis in a Recently Founded Population : Evaluation of the Variegate Porphyria Founder in South African Afrikaners
W. Grody (2007)
10.25911/5d626bf3bc731
Detection of polymorphism in xenobiotic metabolising enzymes using database analysis
N. Tetlow (2003)
10.1089/GTE.1998.2.315
An efficient protocol for rare mutation genotyping in a large population.
H. Zarbl (1998)
10.1093/NAR/30.2.E3
Genetic screening using the colour change of a PNA-DNA hybrid-binding cyanine dye.
L. Wilhelmsson (2002)
10.1146/ANNUREV.GENOM.1.1.329
Sequence variation in genes and genomic DNA: methods for large-scale analysis.
K. Mir (2000)
10.1089/109065703322537223
High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts cystic fibrosis genetic testing.
S. Raskin (2003)
10.1016/S0378-1119(98)00408-9
Single nucleotide polymorphism spectra in newborns and centenarians: identification of genes coding for rise of mortal disease.
A. Tomita-Mitchell (1998)
Technical Standards and Guidelines for CFTR Mutation Testing
G. Feldman (2017)
10.1034/j.1399-0004.2000.570205.x
Molecular genetic testing for familial hypercholesterolemia: spectrum of LDL receptor gene mutations in the Netherlands
M. Lombardi (2000)
See more
Semantic Scholar Logo Some data provided by SemanticScholar