ISOLATION OF COSMIDS AND FETAL BRAIN CDNAS FROM THE PROXIMAL LONG ARMOF HUMAN CHROMOSOME-22

The proximal portion of human chromosome 22q appears to carry genes im plicated in the pathogenesis of various developmental disorders, inclu ding the cat eye syndrome (CES) and the DiGeorge syndrome (DGS). A cos mid library was prepared from a radiation hybrid selected for its cont ent in chromosome 22 fragments. A large fraction of cosmids containing human DNA were found to derive from the juxtacentromeric region of ch romosome 22, as shown by fluorescence in situ hybridization (FISH) per formed using individual cosmids or cosmid pools as probes. Finer mappi ng was obtained for individual cosmids by hybridization to a somatic c ell hybrid mapping panel which splits the long arm of the chromosome i nto 14 bins numbered 1 to 14 from the centromere to the telomere. Of t he 10 cosmids mapped, eight belonged to group 1, the other two to grou p 14, in agreement with FISH data. Rare endonuclease sites and fragmen ts conserved between species were searched in single cosmids, resultin g in the selection of seven cosmid fragments which were used to screen a human fetal brain cDNA library. Three cDNAs were identified, encode d from two chromosome 22 genes which appeared to be novel, as determin ed from partial end sequence and comparison with the database entries. Fine localization of the 30.9 cDNA indicated that the corresponding g ene was located in a segment of proximal 22q overlapping with the crit ical DGS region.