Peaks of Linkage Are Localized by a BAC/PAC Contig of the 6p Reading Disability Locus

Abstract

A gene for reading disability has been localized by nonparametric linkage to 6p21.3–p22 in several published reports. However, the lack of an uninterrupted genomic clone contig has made it difficult to determine accurate intermarker distances, precise marker order, and genetic boundaries and hinders direct comparisons of linkage. The search and discovery of the hemochromatosis gene (HFE) led to the creation of a bacterial artificial chromosome (BAC) and P-1 derived artificial chromosome (PAC) contig that extended physical maps 4 Mb from the MHC toward pter and localized new markers in that region [10-12]. Using this contig, we localized 124 sequence tagged sites, expressed sequence tags, and short tandem repeats including most of the markers in linkage with reading disability phenotypes, succinic semialdehyde dehydrogenase, GPLD1, prolactin, and 18 uncharacterized genes. This new contig joins and extends previously published physical maps to span the entire chromosome 6 reading disability genetic locus. Physical mapping data from the complete contig show overlap of the published linkage peaks for reading disability, provide accurate intermarker distances and order, and offer resources for generating additional markers and candidate genes for highresolution genetic studies in this region.