Construction of a detailed physical and transcript map of the candidate region for Russell-Silver syndrome on chromosome 17q23-q24

Russell-Silver syndrome (RSS) is a heterogeneous disorder characterized mai nly by pre- and postnatal growth retardation and characteristic dysmorphic features. The genetic cause of this syndrome is unknown. However, two autos omal translocations involving chromosome 17q25 were reported in association with RSS. Molecular analysis of the breakpoint on chromosome 17 of the de novo translocation previously described as t(1;17)(q31;q25) enabled us to r efine the localization of the chromosome 17 breakpoint to 17q23-q24. Since no detailed mapping data were available for this region, me established a c ontig of yeast artificial chromosomes, P1 artificial chromosomes, bacterial artificial chromosomes, and cosmid clones for a 17q segment flanked by the sequence-tagged site (STS) markers D17S1557 and D17S940. This contig cover s a physical distance of 4-5 Rib encompassing several novel markers. A tran script map was constructed by assigning genes and expressed sequence tags t o the clone contig, and altogether 74 STS markers were mapped. Furthermore, the locus order and content provide insight into several duplication event s that have occurred in the chromosomal region 17q23-q24. On the basis of o ur refined map, we have reduced the translocation breakpoint region to 65 k b between the newly derived markers 58T7 and CF20b. These data provide the molecular tools for the final identification of the RSS gene in 17q23-q24. (C) 2001 Academic Press.