ISOLATION OF CDNAS FROM THE CRI-DU-CHAT CRITICAL REGION BY DIRECT SCREENING OF A CHROMOSOME 5-SPECIFIC CDNA LIBRARY

Chromosome-specific cDNA libraries are new tools for the isolation of genes From specific genomic regions. We have used two YACs than span t he similar to 2-Mb cri-du-chat critical region (CDCCR) of chromosome 5 p to directly screen a chromosome 5-specific (CH5SP) fetal brain cDNA library. To compare this library with other sources for new gene disco very, the YACs were hybridized to a normalized infant brain (NIB) cDNA library that has been used extensively for expressed sequence tag (ES T) generation. These screens yielded 12 cDNAs from the CH5SP Fetal bra in library and four cDNAs from the NIB library that mapped to discrete intervals within the CDCCR. Four cDNAs mapped within the minimal CDCC R deletion interval, with the remaining cDNAs being located beyond the boundaries. Only one cDNA shared sequence overlap between the CH5SP a nd NIB sets of clones. None of the remaining II CH5SP cDNAs were homol ogous to EST sequences, suggesting ill common with previous data on th ese libraries, that chromosome-specific cDNA libraries are a rich sour ce of new expressed sequences. The single cDNA that did overlap with t he NIB library contained two copies of a sequence motif shared with th rombospondin, properdin, and several complement proteins. This motif i s usually present in adhesive proteins, and appears to mediate cell-ce ll or cell-substrate interactions. This new thrombospondin-like gene, and the other three cDNAs that map within the CDCCR, represent candida te genes for the cri-du-chat contiguous gene deletion syndrome.