SNP and mutation analysis.

Genetic variation and SNP analysis starts with generation of sequence-specific signal, followed by the collection of that signal. The final step is extensive data analysis, which starts with conversion of quantifiable raw data and ends up with identified SNPs, frequencies, and sometimes tissue-specific expression patterns (levels). In this chapter we describe and compare the mechanisms of signal generation of several representative SNP analysis platforms. DNA microarray no doubt has its advantage in applications involving the classification and identification of tumor classes, gene discovery, drug dependent transcription mechanisms, as well as prediction of drug response. PCR, xMAP, invader assay, mass spectrometry, and pyrosequencing, on the other hand, are alternative methods of genotyping employed following the large scale screening and discovery of genetic variations. In addition, they offer higher specificity and sensitivity in analysis of both genomic DNA, as well as RNA. By exploiting these technologies, correlative study of the effects of putative genetic variations on cells, tissue-specific and developmentally specific expression is possible. Of extreme value are the many forms of Mass Spectrometry in the areas of sensitive, early cancer diagnosis. Finally, microarray and xMAP are suitable for protein analysis. While protein array offers higher throughput, xMAP is more amendable to the native 3D structure of protein molecules.

[1]  M. Ronaghi.  Pyrosequencing sheds light on DNA sequencing. , 2001, Genome research.

[2]  C. Nusbaum,et al.  Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. , 1998, Science.

[3]  M. Daly,et al.  A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms , 2001, Nature.

[4]  B. Neri,et al.  Clinical, genetic, and pharmacogenetic applications of the Invader assay. , 1999, Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology.

[5]  N. Hu,et al.  Comprehensive Characterization of Annexin I Alterations in Esophageal Squamous Cell Carcinoma , 2004, Clinical Cancer Research.

[6]  F. Marincola,et al.  Pyrosequencing™ : A one-step method for high resolution HLA typing , 2003, Journal of Translational Medicine.

[7]  P L Smith,et al.  A rapid, sensitive, multiplexed assay for detection of viral nucleic acids using the FlowMetrix system. , 1998, Clinical chemistry.

[8]  D. Lalo,et al.  Oligogenic combinations associated with breast cancer risk in women under 53 years of age , 2005, Human Genetics.

[9]  L. Brooks,et al.  A DNA polymorphism discovery resource for research on human genetic variation. , 1998, Genome research.

[10]  I. Gut,et al.  Facile method for automated genotyping of single nucleotide polymorphisms by mass spectrometry. , 2002, Nucleic acids research.

[11]  L. Tsui,et al.  An RFLP associated with the human catalase gene. , 1985, Nucleic acids research.

[12]  H. Klinger,et al.  Sensitive detection of human papillomavirus in cervical, head/neck, and schistosomiasis-associated bladder malignancies. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Ronaghi,et al.  A Sequencing Method Based on Real-Time Pyrophosphate , 1998, Science.

[14]  E. Lander,et al.  Strategies for studying heterogeneous genetic traits in humans by using a linkage map of restriction fragment length polymorphisms. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Hruban,et al.  LigAmp for sensitive detection of single-nucleotide differences , 2004, Nature Methods.

[16]  B. Neri,et al.  Comparison of detection platforms and post‐polymerase chain reaction DNA purification methods for use in conjunction with Cleavase fragment length polymorphism analysis , 1999, Electrophoresis.

[17]  S. Henikoff,et al.  Accounting for human polymorphisms predicted to affect protein function. , 2002, Genome research.

[18]  E. Gross,et al.  A comparison of BRCA1 mutation analysis by direct sequencing, SSCP and DHPLC , 1999, Human Genetics.

[19]  R. F. Gordon,et al.  Multiplexed quantification of human IgG, IgA, and IgM with the FlowMetrix system. , 1997, Clinical chemistry.

[20]  V. Lyamichev,et al.  Invader assay for SNP genotyping. , 2003, Methods in molecular biology.

[21]  T Foitzi,et al.  Allelic discrimination using fluorogenic probes and the 5' nuclease assay , 1999 .

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

[23]  Michael Krawczak,et al.  The human gene mutation database , 1998, Nucleic Acids Res..

[24]  Sarah Olson,et al.  Quantitation of microRNAs using a modified Invader assay. , 2004, RNA.

[25]  C. Ding,et al.  High-throughput alternative splicing quantification by primer extension and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry , 2005, Nucleic acids research.

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

[27]  S. Adams,et al.  Ambiguous allele combinations in HLA Class I and Class II sequence-based typing: when precise nucleotide sequencing leads to imprecise allele identification , 2004, Journal of Translational Medicine.

[28]  Francis S. Collins,et al.  Erratum: A DNA polymorphism discovery resource for research on human genetic variation (Genome Research (1998) 8 (1229-1231)) , 1999 .

[29]  A. Little,et al.  Mutation detection and typing of polymorphic loci through double-strand conformation analysis , 1998, Nature Genetics.

[30]  E. Petricoin,et al.  SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer. , 2004, Current opinion in biotechnology.

[31]  R. Abramson,et al.  Detection of specific polymerase chain reaction product by utilizing the 5'----3' exonuclease activity of Thermus aquaticus DNA polymerase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  F. Marincola,et al.  DNA Array-Based Gene Profiling in Tumor Immunology , 2004, Clinical Cancer Research.

[33]  A. Little,et al.  High resolution HLA class I typing by reference strand mediated conformation analysis (RSCA). , 1998, Tissue antigens.

[34]  F. Marincola,et al.  A strategy for detection of known and unknown SNP using a minimum number of oligonucleotides applicable in the clinical settings , 2003, Journal of Translational Medicine.

[35]  K. Livak,et al.  Allelic discrimination using fluorogenic probes and the 5' nuclease assay. , 1999, Genetic analysis : biomolecular engineering.

[36]  L J Kricka,et al.  Evaluation of DNA fragment sizing and quantification by the agilent 2100 bioanalyzer. , 2000, Clinical chemistry.