Fine Mapping of the Gene for Carbohydrate-Deficient Glycoprotein Syndrome, Type I (CDG1): Linkage Disequilibrium and Founder Effect in Scandinavian Families

• Published in: Genomics (San Diego, Calif.) Vol. 39; no. 3; pp. 247 - 253
• Main Authors: Bjursell, Cecilia, Stibler, Helena, Wahlström, Jan, Kristiansson, Bengt, Skovby, Flemming, Strömme, Petter, Blennow, Gösta, Martinsson, Tommy
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-02-1997; Elsevier
• Subjects: Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 16; Congenital Disorders of Glycosylation - genetics; Denmark; Female; Founder Effect; Haplotypes; Humans; Linkage Disequilibrium; Male; Malformations of the nervous system; Medical sciences; Neurology; Norway; Pedigree; Sweden; Scandinavia; Europe; Denmark; Norway; Sweden; Peripheral nervous system; Genetic mapping; Human; Linkage; Family study; Metabolic diseases; Founder effect; Genetic disease; Chromosome E16; Central nervous system disease; Genetics; Carbohydrate; Haplotype; Carbohydrate deficient glycoprotein syndrome
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1996.4488

Carbohydrate-deficient glycoprotein syndrome type I (CDG I) is characterized clinically by severe nervous system involvement and biochemically by defects in the carbohydrate residues in a number of serum glycoproteins. The CDG1 gene was recently localized by us to a 13-cM interval in chromosome region 16p13. In this study 44 CDG I families from nine countries were analyzed with available markers in a region ranging from marker D16S495 to D16S497, and haplotype and linkage disequilibrium analyses were performed. One specific haplotype was found to be markedly overrepresented in CDG I patients from a geographically distinct region in Scandinavia, strongly indicating that CDG I families in this region share the same ancestral CDG1 mutation. Furthermore, analysis of the extent of the common haplotype in these families indicates that the CDG1 gene is located in the region defined by markers D16S513–AFMa284wd5–D16S768–D16S406–D16S502. The critical CDG1 region, in strong linkage disequilibrium with markers AFMa284wd5, D16S768, and D16S406, thus constitutes less than 1 Mb of DNA and less than 1 cM in the very distal part of the CDG1 region defined by us previously.