DIRECT GENE DOSAGE DETERMINATION IN PATIENTS WITH UN-BALANCED CHROMOSOMAL-ABERRATIONS USING CLONED DNA-SEQUENCES - APPLICATION TO THE REGIONAL ASSIGNMENT OF THE GENE FOR ALPHA-2(I) PROCOLLAGEN (COLIA2)

  • 1 January 1983
    • journal article
    • research article
    • Vol. 35  (4) , 584-591
Abstract
A new method of direct gene dosage determination is described in patients with unbalanced chromsomal aberrations using cloned DNA sequences: the intensity of the signal obtained by hybridization of the radioactive probe to the corresponding DNA fragments can be compared with the intensity of the DNA fragments that hybridize with a nonsyntenic probe used as an internal control. This was demonstrated by densitometer tracing of the autoradiogram, using an X-specific DNA sequence, .beta. globin and .alpha.2(I) collagen probes, in normal men and women, in one patient trisomic for 11p, and in one patient trisomic for segment 7q21 .fwdarw. 7qter. The ratio men/women for the X-specific sequence (DXS) was close to the expected value 0.5, while the ratio trisomy 11/normal control and trisomy 7/normal control were close to 1.5 for .beta. globin (HBB) and .alpha.2(I) collagen (COLIA2), respectively. The gene coding for COLIA2 can therefore be assigned to 7q21 .fwdarw. 7qter. This method should also apply to noncoding sequences: the increasing number of cloned DNA segments that were already assigned to a specific chromosome represent a new tool for prenatal and premorbid diagnosis of unbalanced chromosomal aberrations.