IDENTIFICATION OF YAC CLONES FOR HUMAN-CHROMOSOME 1P32 AND PHYSICAL MAPPING OF THE INFANTILE NEURONAL CEROID-LIPOFUSCINOSIS (INCL) LOCUS

Infantile neuronal ceroid lipofuscinosis (INCL, CLN1) is a neurodegene rative disorder in which the biochemical defect is unknown. We earlier assigned the disease locus to chromosome 1p32 in the immediate vicini ty of the highly informative HY-TM1 marker by linkage and linkage dise quilibrium analysis. Here we report the construction of PFGE maps on t he CLN1 region covering a total of 4 Mb of this relatively poorly mapp ed chromosomal region. We established the order of loci at 1p32 as 57- L-myc-HY-TM1-rlf-COL9A2-D1S193-D1S62-DIS211-cen by combining data obta ined hom analysis of a chromosome 1 somatic cell hybrid panel, PFGE, a nd interphase FISH, We isolated YACs and constructed two separate YAC contigs, the loci L-myc, HY-TM1, rlf; and COL9A2 being present on a 10 00-kb contig and the markers D1S193, D1S62, and D1S211 on a YAC contig spanning a maximum of 860 kb. Within the 1000-kb contig we were able to identify five CpG islands in addition to those associated with the earlier cloned genes. The YAC contigs as well as the physical map prov ide us with tools for the identification of the INCL gene. (C) 1995 Ac ademic Press, Inc.