HIGH-RESOLUTION PHYSICAL MAP AND IDENTIFICATION OF POTENTIALLY REGULATORY SEQUENCES OF THE HUMAN SH3BGR LOCATED IN THE DOWN-SYNDROME CHROMOSOMAL REGION

We have isolated, mapped and sequenced the 5' promoter region of the h uman SH3BGR (SHS-Binding Glutamine Rich) gene located in the Down synd rome region-2, between markers D21S55 and MX1 of human chromosome 21. This region has been postulated as the minimal region for congenital h eart disease and 6 facial and dermatoglyphic features present in Down syndrome. The SH3BGR gene is expressed in fetal and adult heart and in skeletal muscle and therefore it is a candidate gene for the congenit al heart defect and muscle hypotonia. The 5' region of the gene has be en positioned in a 115 kb PAC/cosmid contig with full EcoRI/SmaI restr iction map covering cosmid pockets 122-123 as well as cosmid pocket 12 4 located between markers D21S268 and D21S220. Sequencing of the SH3BG R promoter region has allowed the identification of several potential regulatory elements of this candidate gene for the congenital heart di sease and other potential DS features. Several of the elements identif ied are also present in other muscle-expressed genes. (C) 1997 Academi c Press.