This chapter focuses on sequencing by hybridization (SBH), an advanced DNA sequencing technique first proposed in 1987 (1). SBH procedures determine DNA sequence information by screening DNA oligomers (typically 7-to 11-mers) for their ability to hybridize with target DNA. The set of ove ...
Antisense oligonucleotides (AONs) are synthetic deoxyribonucleic acids, typically between 15–25 nucleotides, that can bind to complementary sites in a mRNA and inhibit translation. AONs show promise as therapeutics to many diseases caused by abnormal or unwanted expression of a g ...
Over the last few decades, typing for the human leukocyte antigen (HLA) has become critical for bone marrow transplants. Research has also indicated that individuals with certain allelic genotypes may be at a higher risk for developing diseases affecting the immune system, and therefore ra ...
Previous chapters have discussed in detail how to prepare, print and hybridize DNA arrays on various surfaces. Once hybridization is completed, the next step is to scan in the glass, gel, or plastic slides with a specialized scanner to obtain digital images of the results of the experiment. The DNA exp ...
As the Human Genome Project continues toward its goal of characterizing the genome of human and selected model organisms through complete mapping and sequencing of their DNA, unique opportunities are becoming available for studying genetic variation in humans and its relationship w ...
Confocal scanning laser microscopes are best known for making very high-resolution images of small three-dimensional (3D) specimens by recording a series of two-dimensional confocal slices of the specimen at different focus positions. Additionally, confocal microscopes are e ...
In the context of this chapter, biochips are defined as microscale bioanalytical devices that incorporate microfluidic circuitry, highly parallel functionality, or both. Microfluidic circuitry has yielded the lab-on-a-chip concept in which functions such as sample processi ...
Biochips are small platforms with spatially arrayed macromolecules (or pieces thereof) that allow the collection and analysis of large amounts of biological information. The principle of the technology is based on specific molecular recognition interactions between the array ...
It may seem premature to be writing a history of DNA microarrays because this technology is relatively new and clearly has more of a future than a past. However readers could benefit from learning something about the technical basis of DNA microarrays, and younger readers may be curious to know somet ...
By determining an organism’s DNA sequence, researchers can obtain critical information about its development and physiology, its taxonomic relations, and its susceptibility to disease. There are three distinct methods of acquiring DNA sequence information: sequence-speci ...
Since its earliest days, the history of human genetics has been checkered with actual, perceived, and potential abuses in the application of its scientific concepts to research or clinical endeavors. Aside from obvious cases of scientific fraud and continuing controversies over natur ...
High-density polynucleotide probe arrays provide a massively parallel approach to genetic sequence analysis that is having a major impact on biomedical research and clinical diagnostics (1). These arrays are comprised of large sets of nucleic acid probe sequences immobilized in de ...
The ongoing progress in establishing a reference sequence as part of the Human Genome Project (1) has revealed a new challenge: the large-scale identification and detection of intraspecies sequence variations, either between individuals or populations. The information drawn from ...
DNA microarray technologies have been developed as a high-throughput means to study transcriptional regulation (for a recent review, see ref. 1). Large numbers of DNA samples (either complete cDNAs or ESTs) are immobilized as very high-density arrays on solid surfaces, typically glass. M ...
The creation of microspot arrays of bioactive materials has been vigorously pursued by a number of research organizations and commercial companies in the past decade (1,2). In addition to the high density and/or small area achieved by using microspot arrays, increased sensitivity is poss ...
Miniaturization and high-throughput parallel analysis are new concepts entering modern molecular biology. An exciting example of such technology originally developed by physicists and applied to biology is the microchip. The semiconductor industry manufactures silica c ...
Statistics is often thought to concern only the analysis of observational or experimental data. However, experimental design is one of the oldest subfields of statistics. The founder of modern statistics, R. A. Fisher, noted that “statistical procedure and experimental design are only t ...
In this chapter we discuss the problem of identifying differentially expressed genes from a set of microarray experiments. Statistically speaking, this task falls under the heading of “multiple hypothesis testing.” In other words, we must perform hypothesis tests on all genes simulta ...
Clustering is the task of organizing a set of objects into meaningful groups. These groups can be disjoint, overlapping, or organized in some hierarchical fashion. The key element of clustering is the notion that the discovered groups are meaningful. This definition is intentionally vague, ...
Clustering is one of the most commonly used tools in the analysis of gene expression data (1,2). The usage in grouping genes is based on the premise that coexpression is a result of coregulation. It is often used as a preliminary step in extracting gene networks and inference of gene function (3,4). Cluste ...
