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

• Published in: European journal of human genetics : EJHG Vol. 9; no. 3; pp. 217 - 225
• Main Authors: Horsley, S W, Daniels, R J, Anguita, E, Raynham, H A, Peden, J F, Villegas, A, Vickers, M A, Green, S, Waye, J S, Chui, D H, Ayyub, H, MacCarthy, A B, Buckle, V J, Gibbons, R J, Kearney, L, Higgs, D R
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.03.2001
• Subjects: Adolescent; Adult; Base Sequence; Child; Child, Preschool; Chromosome 16; Chromosomes; Chromosomes, Human, Pair 16; Deoxyribonucleic acid; DNA; Evolutionary genetics; Female; Genes; Genetics; Genomes; Genotype & phenotype; Hematology; Hemoglobin; Hospitals; Humans; In Situ Hybridization, Fluorescence; Intellectual disabilities; Male; Middle Aged; Molecular Sequence Data; Monosomy; Patients; Phenotype; Phenotypes; RNA polymerase; Sequence Deletion; Sequence Homology, Nucleic Acid; Signal transduction; Telomere; United Kingdom > UK
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5200610

We have examined the phenotypic effects of 21 independent deletions from the fully sequenced and annotated 356 kb telomeric region of the short arm of chromosome 16 (16p13.3). Fifteen genes contained within this region have been highly conserved throughout evolution and encode proteins involved in important housekeeping functions, synthesis of haemoglobin, signalling pathways and critical developmental pathways. Although a priori many of these genes would be considered candidates for critical haploinsufficient genes, none of the deletions within the 356 kb interval cause any discernible phenotype other than alpha thalassaemia whether inherited via the maternal or paternal 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.