Finding transcribed sequences from specific genomic regions has been a major ratelimiting step in cloning genes involved in human genetic diseases. Early efforts was focused on screening of cDNA library,looking for evolutionarily conserved DNA sequences and northern blot hybridization. In resent years,some new and effective methods have been developed by the Human Genome Project.These methods can not only detect genes regardless of their expression patterns,but also expand the size of the genomic region capable of being scanned for genes. Several new and old methods for were reviewed finding new genes in positional cloning and discuss the advantages and limitations of them.