Polynucleotide Arrays for Genetic Sequence Analysis

We describe a new paradigm for genetic analysis based upon high density arrays of polynucleotide probes. Methods for light-directed polynucleotide array synthesis, as well as array packaging, sample preparation, array hybridization, epifluorescence confocal scanning, and data analysis are described. Applications to discovery, genotyping, expression, and resquencing are presented.

[1]  J. Shaffer,et al.  Hybridization of synthetic oligodeoxyribonucleotides to ΦX 174 DNA: the effect of single base pair mismatch , 1979 .

[2]  Charles R. Cantor,et al.  The behavior of biological macromolecules , 1980 .

[3]  C. Cantor,et al.  Biophysical chemistry. Part III, The behavior of biologicalmacromolecules , 1980 .

[4]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[5]  K. Mullis,et al.  Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. , 1985, Science.

[6]  S. P. Fodor,et al.  Light-directed, spatially addressable parallel chemical synthesis. , 1991, Science.

[7]  S. P. Fodor,et al.  Light-generated oligonucleotide arrays for rapid DNA sequence analysis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[8]  C. G. Willson,et al.  Introduction to microlithography , 1994 .

[9]  S. P. Fodor,et al.  Using oligonucleotide probe arrays to access genetic diversity. , 1995, BioTechniques.

[10]  Steven M. Wolinsky,et al.  Adaptive Evolution of Human Immunodeficiency Virus-Type 1 During the Natural Course of Infection , 1996, Science.

[11]  G. Mcgall,et al.  Light-directed synthesis of high-density oligonucleotide arrays using semiconductor photoresists. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  James L. Winkler,et al.  Accessing Genetic Information with High-Density DNA Arrays , 1996, Science.

[13]  N. Shen,et al.  Extensive polymorphisms observed in HIV–1 clade B protease gene using high–density oligonucleotide arrays , 1996, Nature Medicine.

[14]  S. M. Kim,et al.  Cystic fibrosis mutation detection by hybridization to light‐generated DNA probe arrays , 1996, Human mutation.

[15]  S. P. Fodor,et al.  Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two–colour fluorescence analysis , 1996, Nature Genetics.

[16]  Nam Quoc Ngo,et al.  The Efficiency of Light-Directed Synthesis of DNA Arrays on Glass Substrates , 1997 .