Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7.

Informative polymorphisms have been very difficult to detect in the elastin gene, and this has hampered the analysis of heritable connective tissue disorders, notably the Marfan syndrome. We have recently detected a dinucleotide repeat polymorphism in intron 17 of the human elastin gene consisting of 8 alleles with sizes between 161 and 175 bp. Analysis of 540 chromosomes from unrelated Caucasian individuals revealed a bimodal frequency distribution typical of (dC-dA)n.(dG-dT)n repeat polymorphisms, with allele frequencies ranging from 0.004 (161 bp) to 0.574 (163 bp). As the elastin gene was originally assigned to chromosome 2q31-ter and because more recent data have suggested an assignment to 7q11.1-21.1, we have genotyped a sub-set of the CEPH pedigrees and carried out pairwise linkage analysis with markers on chromosomes 7 and 2. Lod-scores of between +3.70 and +13.69 were obtained with markers spanning 7p13-q22.1, whilst negative lod-scores were observed with the chromosome 2 markers. Analysis of type II human ovarian teratomas placed the elastin gene within 11 cM of the centromere on chromosome 7. Additionally, we detected the dinucleotide repeat in human-rodent cell hybrids containing chromosome 7, but not those containing chromosome 2. These data confirm the assignment of elastin to chromosome 7 and provide a new, highly informative marker for the analysis of heritable disorders of connective tissue for which elastin is a candidate gene.