LINKAGE OF A LOCUS FOR CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME TYPE-I (CDG1) TO CHROMOSOME 16P, AND LINKAGE DISEQUILIBRIUM TO MICROSATELLITE MARKER D16S406

Carbohydrate-deficient glycoprotein syndrome type I is a multisystem d isease with early severe nervous system involvement. The disease, whic h is inherited as an autosomal recessive trait, is biochemically chara cterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in t ransferrin. A whole genome scan was initiated in order to localize the gene (CDG1) with linkage techniques. We analyzed individuals from 25 CDG1 pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome linkage was detected wi th markers located in chromosome region 16p. The lod score (Z(max)) wa s above 8 (theta(max) = 0.00) for several markers in this region. In o rder to further localize the CDG1 gene, recombination and linkage dise quilibrium analyses were performed. Recombination events in some pedig rees indicated that the CDG1 gene is located in a 13 cM interval betwe en microsatellite markers D16S406 and D16S500. Furthermore, allelic as sociation was shown for marker D16S406 indicating that the CDG1 gene i s located close to this. No heterogeneity could be detected in the Eur opean family material tested by us. The positions of cytogenetically l ocalized flanking markers suggest that the location of the CDG1 gene i s in chromosome region 16p13.3 - p13.12.