Molecular Quantitation of Aneuploid Conditions Using Chromosome 21 as a Model

Chromosomal abnormalities occur in 8% of all conceptuses and in 0.7% of all live-born infants. Many of these disorders are characterized by specific phenotypes. Individuals with a particular chromosomal aberration often look more like each other than their siblings. But, as yet, little is understood about the mechanisms that cause the phenotypic abnormalities and developmental delays or which gene products are responsible for a particular physiognomy. The most frequent type of chromosomal abnormality is aneuploidy, which is defined as an abnormal number in the total complement of chromosomes. Of all the aneuploid conditions, the most common is Down syndrome (trisomy 21), which occurs in about 1 of every 800 persons.z Most of the persons with Down syndrome are trisomic for all of chromosome 21 or are mosaics or have translocations of most of chromosome 21. However, a few of these persons are only partially trisomic for chromosome 21. They should prove particularly informative in delineating the region of chromosome 21 that causes the Down syndrome phenotype and in identifying those gene products involved in the syndrome. We have isolated a series of recombinant probes that are specific for the 21st chromosome. Several of these have been regionally mapped by in situ hybridization3 and some have been specifically localized to the region of the chromosome associated with the Down syndrome phenotype. Because it would