SHORT COMMUNICATION Regional Localization of 192 Genic Markers on Human Chromosome 1 T ERRY R OBERTS ,C HARLES AUFFRAY,* AND J OHN K. C OWELL 1 Department of Neurosciences, NC30, Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195; and * Genexpress-Ge ´ne ´thon, BP60, 91002 Evry, and CNRS UPR420, BP8, 94801 Villejuif, France Received March 14, 1996; accepted June 19, 1996 chromosomes following PCR analysis of panels of A panel of somatic cell hybrids has been used to lo- monochromosome somatic cell hybrids (1 – 3, 8, 10, 11, calize 192 novel eSTS markers to seven individual sub- 15, 16, 19, 21, 22, 27, 29). The generation of the eSTS regions of human chromosome 1. The positions of the markers, however, is outstripping their chromosomal breakpoints in each of these hybrids have been deter- assignment; this is even more true for subregional lo- mined relative to the genetic linkage map of chromo- calization, which requires specialized panels of somatic some 1, and so the approximate locations of the genes cell hybrids containing fragments of the chromosomes from which the eSTS markers have been derived can of interest (7, 24). be determined. Although the distribution of the eSTS Human chromosome 1 constitutes about 8.5% of the markers is relatively random, 23% were assigned to human genome (26) and, because of its size, is still the 1p34–p36 region. The hybrid mapping panel does relatively poorly characterized. A recent review of hu- not subdivide the 1q24 – q44 region, which contains man genetic disorders in the Human Genome database 36% of the eSTS markers. This analysis, therefore, pro- that have been assigned to chromosome 1 describes vides a series of genic markers in which to search for candidates for a variety of human genetic disorders over 25 phenotypes for which genes have not yet been and recessive oncogenes mapped to the same relative isolated. Because of our special interest in isolating position on the chromosome.  1996 Academic Press, Inc. the breakpoint junction fragments from patients with a predisposition to neuroblastoma (17, 18), we have characterized a panel of somatic cell hybrids that sub- Genetic loci responsible for human diseases and ma- divide chromosome 1 into seven distinct regions (24). lignancies are constantly being assigned to chromo- The positions of the chromosomal breakpoints in these some regions using a variety of methods including link- hybrids have been determined relative to the genetic age analysis, associations with chromosome rearrange- linkage map described by Gyapay et al. (12). Recently ments, and loss of heterozygosity (LOH) studies. Once (2, 15), a large series of novel eSTS markers were their chromosomal localization has been established, it mapped to the individual human chromosomes. In this is then usually necessary to refine the localization to report we present the subregional localization of a se- isolate it. In many cases this involves the construction ries of these eSTS markers on chromosome 1, which of contiguous arrays (contigs) of overlapping DNA increases the number of candidate genes for the various clones, of which YACs appear to be the most conve- diseases assigned to this chromosome. nient. However, despite recent advances in methodolo- The construction of the somatic cell hybrids used in gies for isolating transcribed sequences from these con- this analysis and the positions of the breakpoints in tigs (5, 9, 20), this is still a very time-consuming and this panel of hybrids were reported by Roberts et al. complicated process. Having established contigs across (24). The chromosome is divided into seven distinct re- the region of interest, however, an alternative ap- gions, and these hybrids have been used to map eSTS proach to identifying the gene responsible for the phe- markers generated as part of the Genexpress program. notype is through the evaluation of potential candidate The hybrid panel was analyzed using PCR and the orig- genes that map to the same region of the chromosome. inal primer pairs (15). A total of 364 eSTS markers The major problem with this approach at the moment, were screened across the hybrid panel but, because not however, is the paucity of genes that have already been all primer pairs produced consistent results and some assigned not only to individual chromosomes but, more showed cross-reactivity with the rodent DNA, it was importantly, to subregions of the chromosome. In a ma- possible to assign only 192 to subregions of the chromo- jor effort to overcome this problem several groups have some. The results of this analysis are shown in Fig. generated expressed sequence-tagged site (eSTS) 1, which demonstrates that the distribution of genes markers, which can then be assigned to individual appears to be relatively even along the length of the chromosome. Because of the numbers involved, how- 1 To whom correspondence should be addressed. 337 GENOMICS 36, 337–340 (1996) ARTICLE NO. 0470 0888-7543/96 $18.00 Copyright  1996 by Academic Press, Inc. All rights of reproduction in any form reserved. AID Genom 4278 / 6r1c$$$101 08-02-96 15:23:26 gnmxal AP: Genomics