Monosomy for the most telomeric, gene-rich region of the short arm of human chromosome 16 causes minimal phenotypic effects

We have examined the phenotypic effects of 21 independent deletions from th e fully sequenced and annotated 356 kb telomeric region of the short arm of chromosome 16 (16p13.3). Fifteen genes contained within this region have b een highly conserved throughout evolution and encode proteins involved in i mportant housekeeping functions, synthesis of haemoglobin, signalling pathw ays and critical developmental pathways. Although a priori many of these ge nes would be considered candidates for critical haploinsufficient genes, no ne of the deletions within the 356 kb interval cause any discernible phenot ype other than alpha thalassaemia whether inherited via the maternal or pat ernal line. These findings contrast with previous observations on patients with larger (> 1 Mb) deletions from the 16p telomere and therefore address the mechanisms by which monosomy gives rise to human genetic disease.