Published in

Wiley, Human Mutation: Variation, Informatics and Disease, 5(30), p. 771-775, 2009

DOI: 10.1002/humu.20944

Links

Tools

Export citation

Search in Google Scholar

Interaction between a chromosome 10RETenhancer and chromosome 21 in the Down syndrome-Hirschsprung disease association

Journal article published in 2009 by Stacey Arnold, Anna Pelet, Jeanne Amiel ORCID, Salud Borrego, Robert Hofstra, Paul Tam, Isabella Ceccherini, Stanislas Lyonnet, Stephanie Sherman, Aravinda Chakravarti
This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

Abstract

Individuals with Down syndrome (DS) display a 40-fold greater risk of Hirschsprung disease (HSCR) than the general population of newborns implicating chromosome 21 in HSCR etiology. Here we demonstrate that the RET enhancer polymorphism RET+9.7 (rs2435357:C>T) at chromosome 10q11.2 is associated with HSCR in DS individuals both by transmission disequilibrium (P=0.0015) and case-control (P=0.0115) analysis of matched cases. Interestingly, the RET+9.7 T allele frequency is significantly different between individuals with DS alone (0.26+/-0.04), HSCR alone (0.61+/-0.04), and those with HSCR and DS (0.41+/-0.04), demonstrating an association and interaction between RET and chromosome 21 gene dosage. This is the first report of a genetic interaction between a common functional variant (rs2435357) and a not infrequent copy number error (chromosome 21 dosage) in two human developmental disorders.