Interaction between a chromosome 10 RET enhancer and chromosome 21 in the down syndrome-hirschsprung disease association

Stacey Arnold; Anna Pelet; Jeanne Amiel; Salud Borrego; Robert Hofstra; Paul Tam; Isabella Ceccherini; Stanislas Lyonnet; Stephanie Sherman; Aravinda Chakravarti

doi:10.1002/humu.20944

Interaction between a chromosome 10 RET enhancer and chromosome 21 in the down syndrome-hirschsprung disease association

Stacey Arnold, Anna Pelet, Jeanne Amiel, Salud Borrego, Robert Hofstra, Paul Tam, Isabella Ceccherini, Stanislas Lyonnet, Stephanie Sherman, Aravinda Chakravarti

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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 19.7 (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 RET19.7 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 RETand 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.

Original language	English (US)
Pages (from-to)	771-775
Number of pages	5
Journal	Human mutation
Volume	30
Issue number	5
DOIs	https://doi.org/10.1002/humu.20944
State	Published - May 2009
Externally published	Yes

Keywords

Complex disorder
Down syndrome
Gene dosage
Hirschsprung disease
RET

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1002/humu.20944

Cite this

@article{dbfcface8f5940de847ef7d7201bdb61,

title = "Interaction between a chromosome 10 RET enhancer and chromosome 21 in the down syndrome-hirschsprung disease association",

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 19.7 (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 RET19.7 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 RETand 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.",

keywords = "Complex disorder, Down syndrome, Gene dosage, Hirschsprung disease, RET",

author = "Stacey Arnold and Anna Pelet and Jeanne Amiel and Salud Borrego and Robert Hofstra and Paul Tam and Isabella Ceccherini and Stanislas Lyonnet and Stephanie Sherman and Aravinda Chakravarti",

year = "2009",

month = may,

doi = "10.1002/humu.20944",

language = "English (US)",

volume = "30",

pages = "771--775",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "Wiley-Liss Inc.",

number = "5",

}

TY - JOUR

T1 - Interaction between a chromosome 10 RET enhancer and chromosome 21 in the down syndrome-hirschsprung disease association

AU - Arnold, Stacey

AU - Pelet, Anna

AU - Amiel, Jeanne

AU - Borrego, Salud

AU - Hofstra, Robert

AU - Tam, Paul

AU - Ceccherini, Isabella

AU - Lyonnet, Stanislas

AU - Sherman, Stephanie

AU - Chakravarti, Aravinda

PY - 2009/5

Y1 - 2009/5

N2 - 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 19.7 (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 RET19.7 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 RETand 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.

AB - 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 19.7 (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 RET19.7 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 RETand 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.

KW - Complex disorder

KW - Down syndrome

KW - Gene dosage

KW - Hirschsprung disease

KW - RET

UR - http://www.scopus.com/inward/record.url?scp=66749168248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66749168248&partnerID=8YFLogxK

U2 - 10.1002/humu.20944

DO - 10.1002/humu.20944

M3 - Article

C2 - 19306335

AN - SCOPUS:66749168248

SN - 1059-7794

VL - 30

SP - 771

EP - 775

JO - Human Mutation

JF - Human Mutation

IS - 5

ER -

Interaction between a chromosome 10 RET enhancer and chromosome 21 in the down syndrome-hirschsprung disease association

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this