REFINED LOCALIZATION OF THE BATTEN-DISEASE GENE (CLN3) BY HAPLOTYPE AND LINKAGE DISEQUILIBRIUM MAPPING TO D16S288-D16S383 AND EXCLUSION FROM THIS REGION OF A VARIANT FORM OF BATTEN-DISEASE WITH GRANULAR OSMIOPHILIC DEPOSITS

Haplotype analysis in a collaborative collection of 143 families with juvenile-onset neuronal ceroid lipofuscinosis (JNCL) or Batten (Spielm eyer-Vogt-Sjogren) disease has permitted refined localization of the d isease gene, CLN3, which was assigned to chromosome 16 in 1989, Recomb ination events in four maternal meioses delimit new flanking genetic m arkers for CLN3 which localize the gene to the chromosome interval 16p 12.1-11.2 between microsatellite markers D16S288 and D16S383, This nar rows the position of CLN3 to a region of 2.1 cM, a significant reducti on from the previous best interval, Using haplotypes, analysis of the strong linkage disequilibrium that exists between genetic markers with in the D16S288-D16S383 interval and CLN3 shows that CLN3 is in closest proximity to loci D16S299 and D16S298, Analysis of markers across the D16S288-D16S383 region in four families with a variant form of JNCL c haracterized histologically by cytosomal granular osmiophilic deposits (GROD) has excluded linkage of the gene locus to the CLN3 region of c hromosome 16, suggesting that JNCL with GROD is not an allelic form of JNCL. (C) 1995 Wiley-Liss, Inc.