The cartilage proteoglycan deficient mutation, nanomelia, contains a DNA polymorphism in the proteoglycan core protein gene that is genetically linked to the nanomelia phenotype.

The avian mutation, nanomelia (nm), is an autosomal recessive embryonic lethal. Homozygous embryos show hypoplasia of the limbs and a parrot-like beak. Biochemical studies have associated this phenotype with the absence of the major cartilage specific proteoglycan core protein (Argraves et al., 1981). Stirpe et al. (1987) demonstrated a reduction in core protein transcripts in nanomelic embryos. Southern analyses did not detect a rearrangement of the core protein gene or a restriction fragment length polymorphism (RFLP) in the core protein gene linked to the nanomelia mutation. These data suggest that the genetic lesion associated with the nanomelia mutation is either a subtle alteration in the core protein gene affecting the biosynthesis of core protein transcript or a defect in a regulatory gene that produces a trans-acting factor requisite for the proper expression of the core protein gene. To distinguish between these two alternative molecular mechanisms for the nanomelia mutation, experiments were conducted to demonstrate genetic linkage or non-linkage of the core protein gene to the nanomelia mutation. Using denaturing gradient gel electrophoresis (DGGE) technology, a DNA polymorphism has been identified at the 3' end of the core protein gene. The polymorphism defines two alleles, one allele is associated with the normal core protein gene, while the other allele always segregates with the nanomelia mutation. These results suggest that the identified DNA polymorphism in the core protein gene is genetically linked to the inheritance of the nanomelic phenotype and the nanomelia mutation contains a lesion in the core protein gene.