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Vol. 10, Issue 8, 1126-1137, August 2000

Genome-wide Detection of Allelic Imbalance Using Human SNPs and High-density DNA Arrays

Rui Mei,1,7 Patricia C. Galipeau,2 Cynthia Prass,3 Anthony Berno,1 Ghassan Ghandour,4 Nila Patil,1 Roger K. Wolff,3 Mark S. Chee,5 Brian J. Reid,2 and David J. Lockhart1,6

1 Affymetrix, Inc., Santa Clara, California 95051 USA; 2 Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 USA; 3 Mercator Genetics, Inc., Menlo Park, California 94025 USA

Most human cancers are characterized by genomic instability, the accumulation of multiple genetic alterations and allelic imbalance throughout the genome. Loss of heterozygosity (LOH) is a common form of allelic imbalance and the detection of LOH has been used to identify genomic regions that harbor tumor suppressor genes and to characterize tumor stages and progression. Here we describe the use of high-density oligonucleotide arrays for genome-wide scans for LOH and allelic imbalance in human tumors. The arrays contain redundant sets of probes for 600 genetic loci that are distributed across all human chromosomes. The arrays were used to detect allelic imbalance in two types of human tumors, and a subset of the results was confirmed using conventional gel-based methods. We also tested the ability to study heterogeneous cell populations and found that allelic imbalance can be detected in the presence of a substantial background of normal cells. The detection of LOH and other chromosomal changes using large numbers of single nucleotide polymorphism (SNP) markers should enable identification of patterns of allelic imbalance with potential prognostic and diagnostic utility.

Present addresses: 4Eos Biotechnology, South San Francisco, CA 94080 USA; 5Illumina, Inc., San Diego, CA 92121 USA; 6Genomics Institute of the Novartis Research Foundation, 3115 Merryfield Row, San Diego, CA 92121

7 Corresponding author.

10:1126-1137 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00
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