ABSTRACT
Achondroplasia (ACH) is a frequent condition of unknown origin characterized by short-limbed dwarfism and macrocephaly. Milder forms, termed hypochondroplasias (HCH) result in short stature with radiological features similar to those observed in ACH. We report on the mapping of a gene causing ACH/HCH to human chromosome 4p16.3, by linkage to the iduronidase A (IDUA) locus, in 15 informative families (Z max = 3.01 at theta = 0 for ACH; Z max = 4.71 at theta = 0 for ACH/HCH). Multipoint linkage analysis provides evidence for mapping the disease locus telomeric to D4S412 (location score in log 10 = 4.60). Moreover, this study supports the view that ACH and HCH are genetically homogeneous in our series.
Subject(s)
Achondroplasia/genetics , Chromosomes, Human, Pair 4 , Chromosome Mapping , Female , Genes, Dominant , Genetic Linkage , Genetic Markers , Humans , Iduronidase/genetics , Male , PedigreeABSTRACT
alpha 2(I) chains of chicken bone collagen were isolated and purified. Analyses confirmed previous studies that the alpha 2(I) chains contained gamma-glutamyl phosphate residues. Sodium borohydride reduction of the gamma-glutamyl phosphate residues of the CaCl2 extracted and purified alpha 2(I) chains and subsequent CNBr cleavage showed that most of the gamma-glutamyl phosphate groups were located on the alpha 2CB3-5 peptides of the type I collagen molecule, suggesting a specific function for these phosphorylated residues. The reported linkage of the Ser(P) containing phosphoproteins of dentin to the alpha 2CB4 regions of collagen may indicate different biological functions for these two different, protein-bound organic phosphate residues.
