File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Fine mapping of the 9q31 Hirschsprung's disease locus
  • Basic View
  • Metadata View
  • XML View
TitleFine mapping of the 9q31 Hirschsprung's disease locus
 
AuthorsTang, CS1
Sribudiani, Y2
Miao, XP1 4
De Vries, AR2
Burzynski, G2 4
So, MT1
Leon, YY1
Yip, BH1
Osinga, J2
Hui, KJWS1
Verheij, JBGM2
Cherny, SS1
Tam, PKH1
Sham, PC1
Hofstra, RMW2 3
GarciaBarceló, MM1
 
Issue Date2010
 
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
 
CitationHuman Genetics, 2010, v. 127 n. 6, p. 675-683 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00439-010-0813-8
 
AbstractHirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 ×9 10-6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCRassociation found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. © 2010 Springer-Verlag.
 
ISSN0340-6717
2013 Impact Factor: 4.522
 
DOIhttp://dx.doi.org/10.1007/s00439-010-0813-8
 
PubMed Central IDPMC2871095
 
ISI Accession Number IDWOS:000277713300007
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 765008M
HKU 775907M
University of Hong Kong200709159003
200611159152
University Grants Committee of Hong KongAoE/M-04/04
University of Hong Kong Genomics Strategic Research Theme
NIHEY-12562
Bernoulle Foundation
NWO901-04-225
Funding Information:

We would like to express our gratitude to all the subjects who participated in the study. This work was supported by grants from the Hong Kong Research Grants Council HKU 765008M and HKU 775907M and The University of Hong Kong Seed Funding 200709159003 and 200611159152 to MGB and PT, respectively. Support was also obtained from the University Grants Committee of Hong Kong (AoE/M-04/04) and from The University of Hong Kong Genomics Strategic Research Theme. SSC and PCS are supported by NIH Grant EY-12562. YS is supported by a grant from the Bernoulle Foundation and GB was supported by a NWO grant (no. 901-04-225).

 
ReferencesReferences in Scopus
 
GrantsGenetic dissection of Hirschsprung's disease
Fine mapping of Hirschsprungs disease loci on the 3p21 and 9q31 candidate regions
Developmental genomics and skeletal research
 
DC FieldValue
dc.contributor.authorTang, CS
 
dc.contributor.authorSribudiani, Y
 
dc.contributor.authorMiao, XP
 
dc.contributor.authorDe Vries, AR
 
dc.contributor.authorBurzynski, G
 
dc.contributor.authorSo, MT
 
dc.contributor.authorLeon, YY
 
dc.contributor.authorYip, BH
 
dc.contributor.authorOsinga, J
 
dc.contributor.authorHui, KJWS
 
dc.contributor.authorVerheij, JBGM
 
dc.contributor.authorCherny, SS
 
dc.contributor.authorTam, PKH
 
dc.contributor.authorSham, PC
 
dc.contributor.authorHofstra, RMW
 
dc.contributor.authorGarciaBarceló, MM
 
dc.date.accessioned2012-02-21T05:42:58Z
 
dc.date.available2012-02-21T05:42:58Z
 
dc.date.issued2010
 
dc.description.abstractHirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 ×9 10-6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCRassociation found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. © 2010 Springer-Verlag.
 
dc.description.naturepublished_or_final_version
 
dc.description.otherSpringer Open Choice, 21 Feb 2012
 
dc.identifier.citationHuman Genetics, 2010, v. 127 n. 6, p. 675-683 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00439-010-0813-8
 
dc.identifier.citeulike6956535
 
dc.identifier.doihttp://dx.doi.org/10.1007/s00439-010-0813-8
 
dc.identifier.eissn1432-1203
 
dc.identifier.epage683
 
dc.identifier.hkuros170748
 
dc.identifier.isiWOS:000277713300007
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 765008M
HKU 775907M
University of Hong Kong200709159003
200611159152
University Grants Committee of Hong KongAoE/M-04/04
University of Hong Kong Genomics Strategic Research Theme
NIHEY-12562
Bernoulle Foundation
NWO901-04-225
Funding Information:

We would like to express our gratitude to all the subjects who participated in the study. This work was supported by grants from the Hong Kong Research Grants Council HKU 765008M and HKU 775907M and The University of Hong Kong Seed Funding 200709159003 and 200611159152 to MGB and PT, respectively. Support was also obtained from the University Grants Committee of Hong Kong (AoE/M-04/04) and from The University of Hong Kong Genomics Strategic Research Theme. SSC and PCS are supported by NIH Grant EY-12562. YS is supported by a grant from the Bernoulle Foundation and GB was supported by a NWO grant (no. 901-04-225).

 
dc.identifier.issn0340-6717
2013 Impact Factor: 4.522
 
dc.identifier.issue6
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2871095
 
dc.identifier.pmid20361209
 
dc.identifier.scopuseid_2-s2.0-77953443007
 
dc.identifier.spage675
 
dc.identifier.urihttp://hdl.handle.net/10722/144968
 
dc.identifier.volume127
 
dc.languageEng
 
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00439/index.htm
 
dc.publisher.placeGermany
 
dc.relation.ispartofHuman Genetics
 
dc.relation.projectGenetic dissection of Hirschsprung's disease
 
dc.relation.projectFine mapping of Hirschsprungs disease loci on the 3p21 and 9q31 candidate regions
 
dc.relation.projectDevelopmental genomics and skeletal research
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThe Author(s)
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshCarrier Proteins - genetics
 
dc.subject.meshChromosomes, Human, Pair 9
 
dc.subject.meshHirschsprung Disease - genetics
 
dc.subject.meshPhysical Chromosome Mapping - methods
 
dc.subject.meshProto-Oncogene Proteins c-ret - genetics
 
dc.titleFine mapping of the 9q31 Hirschsprung's disease locus
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Tang, CS</contributor.author>
<contributor.author>Sribudiani, Y</contributor.author>
<contributor.author>Miao, XP</contributor.author>
<contributor.author>De Vries, AR</contributor.author>
<contributor.author>Burzynski, G</contributor.author>
<contributor.author>So, MT</contributor.author>
<contributor.author>Leon, YY</contributor.author>
<contributor.author>Yip, BH</contributor.author>
<contributor.author>Osinga, J</contributor.author>
<contributor.author>Hui, KJWS</contributor.author>
<contributor.author>Verheij, JBGM</contributor.author>
<contributor.author>Cherny, SS</contributor.author>
<contributor.author>Tam, PKH</contributor.author>
<contributor.author>Sham, PC</contributor.author>
<contributor.author>Hofstra, RMW</contributor.author>
<contributor.author>GarciaBarcel&#243;, MM</contributor.author>
<date.accessioned>2012-02-21T05:42:58Z</date.accessioned>
<date.available>2012-02-21T05:42:58Z</date.available>
<date.issued>2010</date.issued>
<identifier.citation>Human Genetics, 2010, v. 127 n. 6, p. 675-683</identifier.citation>
<identifier.issn>0340-6717</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/144968</identifier.uri>
<description.abstract>Hirschsprung&apos;s disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 &#215;9 10-6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCRassociation found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. &#169; 2010 Springer-Verlag.</description.abstract>
<language>Eng</language>
<publisher>Springer Verlag. The Journal&apos;s web site is located at http://link.springer.de/link/service/journals/00439/index.htm</publisher>
<relation.ispartof>Human Genetics</relation.ispartof>
<rights>The Author(s)</rights>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<subject.mesh>Carrier Proteins - genetics</subject.mesh>
<subject.mesh>Chromosomes, Human, Pair 9</subject.mesh>
<subject.mesh>Hirschsprung Disease - genetics</subject.mesh>
<subject.mesh>Physical Chromosome Mapping - methods</subject.mesh>
<subject.mesh>Proto-Oncogene Proteins c-ret - genetics</subject.mesh>
<title>Fine mapping of the 9q31 Hirschsprung&apos;s disease locus</title>
<type>Article</type>
<identifier.openurl>http://library.hku.hk:4551/resserv?sid=springerlink&amp;genre=article&amp;atitle=Fine mapping of the 9q31 Hirschsprung&#8217;s disease locus&amp;title=Human Genetics&amp;issn=03406717&amp;date=2010-06-01&amp;volume=127&amp;issue=6&amp; spage=675&amp;authors=C. S. Tang, Y. Sribudiani, X. P. Miao, &lt;i&gt;et al.&lt;/i&gt;</identifier.openurl>
<description.nature>published_or_final_version</description.nature>
<identifier.doi>10.1007/s00439-010-0813-8</identifier.doi>
<identifier.pmid>20361209</identifier.pmid>
<identifier.pmcid>PMC2871095</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-77953443007</identifier.scopus>
<identifier.hkuros>170748</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-77953443007&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>127</identifier.volume>
<identifier.issue>6</identifier.issue>
<identifier.spage>675</identifier.spage>
<identifier.epage>683</identifier.epage>
<identifier.eissn>1432-1203</identifier.eissn>
<identifier.isi>WOS:000277713300007</identifier.isi>
<publisher.place>Germany</publisher.place>
<description.other>Springer Open Choice, 21 Feb 2012</description.other>
<relation.project>Genetic dissection of Hirschsprung&apos;s disease</relation.project>
<relation.project>Fine mapping of Hirschsprungs disease loci on the 3p21 and 9q31 candidate regions</relation.project>
<relation.project>Developmental genomics and skeletal research</relation.project>
<identifier.citeulike>6956535</identifier.citeulike>
<bitstream.url>http://hub.hku.hk/bitstream/10722/144968/1/439_2010_Article_813.pdf</bitstream.url>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Universitair Medisch Centrum Groningen
  3. Huazhong University of Science and Technology
  4. The Johns Hopkins School of Medicine