A highly polymorphic (ACT)n VNTR (variable nucleotide of tandem repeats) locus inside intron 12 of COL1A2, one of the two genes involved in dominant osteogenesis imperfecta.

A new, highly polymorphic, region consisting of variable number of tandem repeats (VNTR) is described that occurs within intron 12 of the COL1A2 gene. This VNTR consists of the trinucleotide ACT repeated from 6 to 12 times. Of the six alleles so far detected four are common in the three major races. The two rare alleles, (ACT)11 and (ACT)12, have been found only in Africans. In addition, a rapid technique has been developed that can be used successfully with very small amounts of even partially degraded DNA, thus allowing the use of this VNTR for forensic applications. Since dominant OI can be due to mutations at either of two loci (COL1A1 and COL1A2) prenatal diagnosis becomes feasible in the majority of the affected families only if a very informative marker is available for both of these genes. This VNTR provides a very powerful marker for COL1A2. In fact the heterozygosity for it ranges from 0.634 to 0.741 with PIC values from 0.562 to 0.696, respectively. Since trinucleotide repeats can be "unstable," and sometimes pathogenic, the unexplained collagenopathies (or suspected collagenopathies) should be analyzed from this point of view.