CLONING AND DEVELOPMENTAL EXPRESSION ANALYSIS OF CHICK HIRA (CHIRA), A CANDIDATE GENE FOR DIGEORGE-SYNDROME

Deletions within human chromosome 22q11 cause a wide variety of birth defects including the DiGeorge syndrome and velo-cardio-facial (Shprin tzen) syndrome, Despite the positional cloning of several genes from t he critical region, it is still not possible to state whether the phen otype is secondary to haploinsufficiency of one or more than one gene, In embryological studies phenocopies of these abnormalities are produ ced by a variety of actions which disrupt the contribution made by the cranial and cardiac neural crest to development, The TUPLE1/HIRA gene is related to WD40 domain transcriptional regulators and maps within the DiGeorge critical region, We have cloned the chick homologue of HI RA and conducted in situ expression analysis in early chick embryos. H IRA is expressed in the developing neural plate, the neural tube, neur al crest and the mesenchyme of the head and branchial arch structures, HIRA may therefore have a role in the haploinsufficiency syndromes ca used by deletion of 22q11.