COMPUTERIZED POLYMORPHIC MARKER IDENTIFICATION - EXPERIMENTAL VALIDATION AND A PREDICTED HUMAN POLYMORPHISM CATALOG

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verifie d. A suite of programs, collectively called POMPOUS (polymorphic marke r prediction of ubiquitous simple sequences) detects tandem repeats ra nging from dinucleotides up to 250 mers, scores them according to pred icted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p213, involved in lung and b reast carcinoma homozygous deletions. Target DNA from 36 paired B lymp hoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size,We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42 , Allele loss in this region was found in 27/36 (75%) of the tumor lin es using these markers. POMPOUS provides the genetic researcher with a n additional tool for the rapid and efficient identification of polymo rphic markers, and through a World Wide Web site, investigators can us e POMPOUS to identify polymorphic markers for their research. A catalo g of 13,261 potential polymorphic markers and associated primer sets h as been created from the analysis of 141,779,504 base pairs of human g enomic sequence in GenBank. This data is available on our Web site (po mpous.swmed.edu) and will be updated periodically as GenBank is expand ed and algorithm accuracy is improved.