Expression of Genes on Human Chromosome 21

Abstract

Gene sequences were isolated from a lambda library containing inserts originating from human chromosome 21. One phage, CP21G1, had been selected on the basis of its lack of middle-repetitive sequences and its ability to hybridize with 32P-labeled cDNA synthesized from the cytoplasmic poly A+ RNA of cultured fibroblasts. Further experiments revealed that the human insert in this phage is unique-sequence DNA, maps to the long arm of chromosome 21, and is expressed in fibroblasts and T cells. A panel of 127 "unique-sequence" phage were also selected from the lambda library and were tested for hybridization to 32P-labeled cDNA synthesized from the cytoplasmic poly A+ RNA of CCRF-HSB-2, a T-blast leukemic line. Seventeen recombinants hybridized to the probe. One of these phages, CP8, contains a human unique-sequence DNA expressed in T cells and neuroblastoma cells. One phage (CP5) in the "unique-sequence" panel that had not hybridized to cDNA from T-cell RNA was found to carry a low-repeat sequence and to hybridize specifically to RNA from a neuroblastoma line. This phage appears to carry a brain-specific gene. Many of the genomic sequences related to the low-repeat sequence contained in CP5 map to the short arm of chromosome 21. The cloned genes described here represent new markers for the detailed mapping of human chromosome 21 and may prove valuable in studying tissue-specific gene regulation.