Use of a chromosome 21 cloned DNA probe for the analysis of non-disjunction in Down syndrome.

A recombinant clone was isolated containing a sequence which occurs only on human chromosome 21 and defines a two-allele restriction fragment length polymorphism showing Mendelian inheritance. Forty seven percent of the London population are heterozygous for the polymorphism. The chromosomal location of the DNA sequence homologous to the probe was confirmed using rodent-human somatic cell hybrids. DNA from persons with Down syndrome and from their parents was analysed. It was possible to confirm trisomy 21 by dosage hybridisation to Southern blots, and to determine the origin of the supernumerary chromosome. The technique will be of use for determination of the paternal or maternal origin of nondisjunction in cases of Down syndrome which are not informative using existing markers.