Molecular Genetics

Types I-IV OI are associated with mutations in the COL1A1 and COL1A2 genes that encode the two a1(I)

and one a2(I) chains, respectively, of the type I collagen trimer (Database of Human Type I and Type III Collagen Mutations: http://www.le.ac.uk/genetics/collagen). Type I collagen is the major structural protein of bones, skin, ligaments, tendons, and most other connective tissues. It is synthesized as a soluble procollagen, containing globular propeptides at the ends of each chain. Cleavage of propeptides generates the collagen that self-assembles into fibrils, which are the major source of mechanical strength of connective tissues and the template for matrix deposition and mineralization in the bones. The chains comprising the triple-helical domain of type I collagen are constructed from repeating Gly-X-Y triplets, in which X and Y can be any amino or imino acid (except for tryptophan or cysteine). Glycine, with its small side chain, is essential at every third position for triple-helix formation. The most common mutations (about 85%) are single-base substitutions in the triple-helical domain that change a codon for a glycine to a codon for another amino acid with a charged, polar, or bulky side chain. Replacement of glycine by serine, cysteine, alanine, valine, aspartic acid, glutamic acid, arginine, and trypto-phan has been identified, with serine being the most common and tryptophan being exceedingly rare. Another substantial group of mutations (about 12%) consists of single-exon splicing defects, and the remaining mutations include nonsense substitutions, frameshift or in-frame deletions, and insertions. The nonsense substitutions and frameshift mutations have not been detected in the COL1A2 gene. The genetic defect underlying types V and VI OI remains to be elucidated, as it does not appear to be associated with collagen type I mutations. In the case of type VII OI, the existence of extended affected families has enabled the chromosome location of the gene defect to be mapped to chromosome 3p22-24.1.[5]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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