Accessing Genetic Information with High-Density DNA Arrays

Rapid access to genetic information is central to the revolution taking place in molecular genetics. The simultaneous analysis of the entire human mitochondrial genome is described here. DNA arrays containing up to 135,000 probes complementary to the 16.6-kilobase human mitochondrial genome were generated by light-directed chemical synthesis. A two-color labeling scheme was developed that allows simultaneous comparison of a polymorphic target to a reference DNA or RNA. Complete hybridization patterns were revealed in a matter of minutes. Sequence polymorphisms were detected with single-base resolution and unprecedented efficiency. The methods described are generic and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability.

[1]  M. Gordon,et al.  THE ACTION OF METAL IONS ON TOBACCO MOSAIC VIRUS RIBONUCLEIC ACID. , 1964, Biochemistry.

[2]  G. Eichhorn,et al.  Interactions of metal ions with polynucleotides and related compounds. IV. Degradation of polyribonucleotides by zinc and other divalent metal ions , , 1965, Biopolymers.

[3]  P. V. von Hippel,et al.  Alteration of the relative stability of dA-dT and dG-dC base pairs in DNA. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[4]  W. Gilbert,et al.  A new method for sequencing DNA. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[5]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[6]  F. Sanger,et al.  Sequence and organization of the human mitochondrial genome , 1981, Nature.

[7]  M. Stoneking,et al.  Mitochondrial DNA and human evolution , 1987, Nature.

[8]  W. Bains,et al.  A novel method for nucleic acid sequence determination. , 1988, Journal of theoretical biology.

[9]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[10]  R. Drmanac,et al.  Sequencing of megabase plus DNA by hybridization: theory of the method. , 1989, Genomics.

[11]  N. Bresolin,et al.  Nucleus-driven multiple large-scale deletions of the human mitochondrial genome: a new autosomal dominant disease. , 1990, American journal of human genetics.

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

[13]  M. Stoneking,et al.  Population variation of human mtDNA control region sequences detected by enzymatic amplification and sequence-specific oligonucleotide probes. , 1991, American journal of human genetics.

[14]  D. Wallace,et al.  Leber's hereditary optic neuropathy: a model for mitochondrial neurodegenerative diseases , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  M. Stoneking,et al.  Complete mitochondrial genome amplification , 1994, Nature Genetics.

[16]  M. Giulio.  On the Origin of Protein Synthesis: A Speculative Model Based on Hairpin RNA Structures , 1994 .

[17]  G. Cortopassi,et al.  A mitochondrial DNA clone is associated with increased risk for Alzheimer disease. , 1995, Proceedings of the National Academy of Sciences of the United States of America.