K. Foster et al., DESCRIPTION OF A DINUCLEOTIDE REPEAT POLYMORPHISM IN THE HUMAN ELASTIN GENE AND ITS USE TO CONFIRM ASSIGNMENT OF THE GENE TO CHROMOSOME-7, Annals of Human Genetics, 57, 1993, pp. 87-96
Informative polymorphisms have been very difficult to detect in the el
astin gene. and this has hampered the analysis of heritable connective
tissue disorders, notably the Marfan syndrome. We have recently detec
ted a dinucleotide repeat polymorphism in intron 17 of the human elast
in gene consisting of 8 alleles with sizes between 161 and 175 bp. Ana
lysis 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 chromos
ome 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 a
nd 2. Lod-scores of between + 3.70 and + 13.69 were obtained with mark
ers spanning 7p13-q22.1, whilst negative lod-scores were observed with
the chromosome 2 markers. Analysis of type 11 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 c
ell hybrids containing chromosome 7, but not those containing chromoso
me 2. These data confirm the assignment of elastin to chromosome 7 and
provide a new, highly informative marker for the analysis of heritabl
e disorders of connective tissue for which elastin is a candidate gene
.