OVERALL INFORMATIVITY, OI, IN DNA POLYMORPHISMS REVEALED BY INTER-ALUPCR - DETECTION OF GENOMIC REARRANGEMENTS

We studied two systems of multilocus markers revealed by PCR using pri mers directing amplification between Alu repeats in a tail-to-tail ori entation. Genomic polymorphisms were detected as the presence or absen ce of the electrophoretic bands representing DNA fragments of a given length. A total of 104 such fragments segregating as Mendelian markers in a panel of eight CEPH families were analyzed by two-point linkage analysis. Fifty-one of these fragments were localized with respect to CEPH markers; they represented 33 loci, 7 of which were multiallelic. Locus-specific oligonucleotides were developed and used as hybridizati on probes to identify the mapped loci within a complex pattern of inte r-Alu PCR products. A great proportion of inter-Alu PCR polymorphisms represented length variants within amplified DNA segments, while other s were presumably due to mutations within the priming sites. To descri be the expected number of informative loci per typing experiment we in troduced a parameter called overall informativity (OI), which provides a single measure of the multiplex ratio and the informativity of mark ers contributing to a multilocus system (OI of a single locus is equiv alent to its heterozygosity and cannot exceed 0.5 for a biallelic codo minant marker), High OI values (5.8 and 11.5) of the two presented sys tems of inter-Alu PCR markers of random chromosomal distribution rende r them suitable for mapping genomic rearrangements such as genomic del etions in tumoral tissues. This was illustrated by the detection of lo ss of heterozygosity in the 9q22-qter region in sporadic colon cancer. (C) 1996 Academic Press, Inc.