Physical and Transcriptional Map of a 3-Mb Region of Mouse Chromosome 1 Containing the Gene for the Neural Tube Defect Mutantloop-tail(Lp)

Abstract

TheLpmouse mutant provides a model for the severe human neural tube defect (NTD), cranio-rachischisis. To identify theLpgene, a positional cloning approach has been adopted. Previously, linkage analysis in a large intraspecific backcross was used to map theLplocus to distal mouse chromosome 1. Here we report a detailed physical map of this region. The interval surroundingLphas been cloned in a yeast artificial chromosome (YAC) contig consisting of 63 clones spanning approximately 3.2 Mb. Fifty sequence tagged sites (STSs) have been used to construct the contig and establish marker order across the interval. Based on the high level of conserved synteny between distal mouse chromosome 1 and human 1q21–q24, many of these STSs were designed from expressed sequences identified by cross-screening human and mouse databases of expressed sequence tags. Added to other known genes in the region, a total of 29 genes were located and ordered within the contig. Seven novel polymorphisms were identified within the region, allowing refinement of the genetic map and a reduction in the size of the physical interval containing theLpgene. TheLpinterval, betweenD1Mit113andTagln2,can be spanned by two nonchimeric overlapping YACs that define a physical distance of ∼1 Mb. Within this region, 10 potential candidate genes have been mapped. The materials and genes described here will provide a resource for the identification and further study of the mutatedLpgene that causes this severe neural tube defect and will provide candidates for other defects known to map to the homologous region on human chromosome 1q.