SEQUENCE VARIATION IN GENES AND GENOMIC DNA: Methods for Large-Scale Analysis

• Published in: Annual review of genomics and human genetics Vol. 1; no. 1; pp. 329 - 360
• Main Authors: Mir, Kalim U, Southern, Edwin M
• Format: Journal Article
• Language: English
• Published: Palo Alto, CA 94303-0139 Annual Reviews 01-01-2000; 4139 El Camino Way, P.O. Box 10139; USA
• Subjects: arrays; Base Sequence; chips; DNA - genetics; DNA chip/array platform; Genetic Variation; Genotype; genotyping; Globins - genetics; Haplotypes; Humans; Mass Spectrometry; Mutation; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; polymorphism; Polymorphism, Single Nucleotide; Sequence Analysis, DNA - methods
• ISSN: 1527-8204; 1545-293X
• DOI: 10.1146/annurev.genom.1.1.329

The large-scale typing of sequence variation in genes and genomic DNA
presents new challenges for which it is not clear that current technologies are
sufficiently sensitive, robust, or scalable. This review surveys the current
platform technologies: separation-based approaches, which include mass
spectrometry; homogeneous assays; and solid-phase/array-based assays. We assess
techniques for discovering and typing variation on a large scale, especially
that of single-nucleotide polymorphisms. The in-depth focus is the DNA
chip/array platform, and some of the published large-scale studies are closely
examined. The problem of large-scale amplification is addressed, and emerging
technologies for present and future needs are indicated.