An expression-independent catalog of genes from human chromosome 22.

To accomplish large-scale identification of genes from a single human chromosome, exon amplification was applied to large pools of clones from a flow-sorted human chromosome 22 cosmid library. Sequence analysis of more than one-third of the 6400 cloned products identified 35% of the known genes previously localized to this chromosome, as well as several unmapped genes and randomly sequenced cDNAs. Among the more interesting sequence similarities are those that represent novel human genes that are related to others with known or putative functions, such as one exon from a gene that may represent the human homolog of Drosophila Polycomb. it is anticipated that sequences from at least half of the genes residing on chromosome 22 are contained within this exon library. This approach is expected to facilitate fine-structure physical and transcription mapping of human chromosomes, and accelerate the process of disease gene identification. A primary goal of the human genome initiative is the construction of fine-structure physical maps of the chromosomes in anticipation of full DNA sequence analysis. However, probably the most important purpose of this mapping, the identification and placement of human genes, can be carried out effectively before determining the complete sequence of the human genome, and can aid in increasing the resolution of the physical map. Low-resolution physical maps of human chromosomes have been described recently (Cohen et al. 1993), but considerably greater detail is needed to maximize their utility and proceed with large-scale sequencing. Identification of a representative set of genes or gene fragments corresponding to a specific genomic region would satisfy many of the requirements for finer mapping and would add a level of functional significance to these evolving maps. The resulting gene, or transcription maps, would provide a new framework for the study of structural, functional, and organizational aspects of chromosomes, and would lead to more efficient identification of genes involved in human disease. Consequently, recently the development of methods for rapid gene identification has received greater attention, and numerous strategies, including ap