q5 - lynna

[ArchivalUser]

40.
A newborn female has a large and distorted cranium, short and deformed limbs, and very blue scleras (whites of the eyes). Radiographs demonstrate multiple limb fractures and suggest a diagnosis of osteogenesis imperfecta (brittle bone disease). Analysis of type I collagen protein, a triple helix formed from two 1 and one 2 collagen chains, shows a 50% reduction in the amount of type I collagen in the baby's skin. DNA analysis demonstrates the presence of two normal 1 alleles and one normal 2 allele. Which of the following is the best explanation of these results?
A. Deficiency of 1 collagen peptide synthesis
B. Inability of 1 chains to incorporate into triple helix
C. Defective 1 chains that interrupt triple helix formation
D. Incorporation of defective 2 chains that cause instability and degradation of the triple helix
E. A missense mutation that alters the synthesis of 1 chains

[ArchivalUser]

d?

[ArchivalUser]

guessing D.

[ArchivalUser]

The answer is: D

Collagen peptides assemble into helical tertiary structures that form quaternary triple helices. The triple helices in turn assemble end to end to form collagen fibrils that are essential for connective tissue strength. Over 15 types of collagen contribute to the connective tissue of various organs, including the contribution of type I collagen to eyes, bones, and skin. The fact that only one of two 2 alleles is normal in this case implies that a mutant 2 allele could be responsible for the disease (even if the 2 locus is on the X chromosome, since the baby is female with two X chromosomes). The mutant 2 collagen peptide would be incorporated into half of the type I collagen triple helices, causing a 50% reduction in normal type I collagen. (A mutant 1 collagen peptide would distort 75% of the molecules since two 1 peptides go into each triple helix.) The ability of one abnormal collagen peptide allele to alter triple-helix structure with subsequent degradation is well documented and colorfully named protein suicide or, more properly, a dominant-negative mutation