Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3
The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2 , in which three causal, unc...
Gespeichert in:
| Veröffentlicht in: | Genes and immunity 2013-07, Vol.14 (5), p.310-316 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 316 |
|---|---|
| container_issue | 5 |
| container_start_page | 310 |
| container_title | Genes and immunity |
| container_volume | 14 |
| creator | Zhang, W Hui, K Y Gusev, A Warner, N Ng, S M E Ferguson, J Choi, M Burberry, A Abraham, C Mayer, L Desnick, R J Cardinale, C J Hakonarson, H Waterman, M Chowers, Y Karban, A Brant, S R Silverberg, M S Gregersen, P K Katz, S Lifton, R P Zhao, H Nuñez, G Pe'er, I Peter, I Cho, J H |
| description | The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at
NOD2
, in which three causal, uncommon and conditionally independent
NOD2
variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with
P
-value |
| doi_str_mv | 10.1038/gene.2013.19 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3785105</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A341262139</galeid><sourcerecordid>A341262139</sourcerecordid><originalsourceid>FETCH-LOGICAL-c584t-318ba5464a3f8afd903af52f1313f8f05fdc8b392384783458e6ca4fc8d4d7673</originalsourceid><addsrcrecordid>eNqNksFu1DAQhiMEoqVw44wscQFps9ix4ySXSstqS4sqkEo5W64z3rhk7RA7bZcTr4HEk_AQPARPgqMtLYt6QD7Ymvnm1_zjSZKnBE8JpuWrJViYZpjQKanuJbuEFTzNWYHvj2_OU1YW1U7yyPtzjAknvHqY7GSUkxwX2W7yfXEVwNZQo0Z2rQvrDpD03ikjg3EW-TDUa2Qsmveusb--fvOoNh6kB2RqsMFoAx5JZN0FtBM0880nsPKLQW_h0vgm9R2oyCi0Mt6DjWWrIWyko2hoAL07SH_-eI06GZpLuUajnQk6XMxOT-jj5IGWrYcn1_de8vFgcTo_TI_fvzmaz45TlZcspJSUZzJnnEmqS6nrClOp80wTSmJA41zXqjyjVUZLVpSU5SVwJZlWZc3qghd0L9nf6HbD2QpqFX31shVdb1ayXwsnjdjOWNOIpbsQtChzgvMo8OJaoHefB_BBRLsK2lZacIMXhJGKFpgS9j8oJTyveBbR5_-g527obZyEyDgjBeUFo7fUUrYgjNUutqhGUTGjjGQ8I7SK1PQOKp4aVkY5C9rE-FbBy62CyAS4Cks5eC-OPpxss5MNq3rnfQ_6ZnQEi3FJxfirYlxSQUb82d_jvoH_bGUE0g3gY8ouob81fqfgb1tI8pY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2641736743</pqid></control><display><type>article</type><title>Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>Zhang, W ; Hui, K Y ; Gusev, A ; Warner, N ; Ng, S M E ; Ferguson, J ; Choi, M ; Burberry, A ; Abraham, C ; Mayer, L ; Desnick, R J ; Cardinale, C J ; Hakonarson, H ; Waterman, M ; Chowers, Y ; Karban, A ; Brant, S R ; Silverberg, M S ; Gregersen, P K ; Katz, S ; Lifton, R P ; Zhao, H ; Nuñez, G ; Pe'er, I ; Peter, I ; Cho, J H</creator><creatorcontrib>Zhang, W ; Hui, K Y ; Gusev, A ; Warner, N ; Ng, S M E ; Ferguson, J ; Choi, M ; Burberry, A ; Abraham, C ; Mayer, L ; Desnick, R J ; Cardinale, C J ; Hakonarson, H ; Waterman, M ; Chowers, Y ; Karban, A ; Brant, S R ; Silverberg, M S ; Gregersen, P K ; Katz, S ; Lifton, R P ; Zhao, H ; Nuñez, G ; Pe'er, I ; Peter, I ; Cho, J H</creatorcontrib><description>The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at
NOD2
, in which three causal, uncommon and conditionally independent
NOD2
variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with
P
-value <10
−3
, respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in
TRPM2
on chromosome 21. Within the chromosome 16 region, R642S of
HEATR3
and rs9922362 of
BRD7
showed genome-wide significance. Expression studies of
HEATR3
demonstrated a positive role in NOD2-mediated NF-κB signaling. The
BRD7
signal showed conditional dependence with only the downstream rare CD-causal variants in
NOD2
, but not with the background haplotype; this elaborates
NOD2
as a key illustration of synthetic association.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/gene.2013.19</identifier><identifier>PMID: 23615072</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/205 ; 631/208/727/728 ; 631/250/516/1909 ; 692/699/249/2510/1402 ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cellular signal transduction ; Chromosomal Proteins, Non-Histone - genetics ; Chromosome 16 ; Chromosome 21 ; Chromosomes, Human, Pair 16 - genetics ; Crohn Disease - genetics ; Crohn's disease ; Demographic aspects ; Development and progression ; Etiology ; Exons - genetics ; Gene Expression ; Gene mutations ; Genetic aspects ; Genetic Predisposition to Disease - genetics ; Genome-Wide Association Study ; Genomes ; Genotype ; Genotyping ; Haplotypes ; HEK293 Cells ; Human Genetics ; Humans ; Immunology ; Jewish people ; Jews - genetics ; Logistic Models ; Missense mutation ; Mutation, Missense ; NF-kappa B - genetics ; NF-κB protein ; NOD2 ; NOD2 protein ; Nod2 Signaling Adaptor Protein - genetics ; original-article ; Physiological aspects ; Polymorphism, Single Nucleotide ; Population ; Proteins - genetics ; RNA Interference ; Sequence Analysis, DNA ; Signal Transduction - genetics ; Transient receptor potential proteins</subject><ispartof>Genes and immunity, 2013-07, Vol.14 (5), p.310-316</ispartof><rights>Macmillan Publishers Limited 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2013.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-318ba5464a3f8afd903af52f1313f8f05fdc8b392384783458e6ca4fc8d4d7673</citedby><cites>FETCH-LOGICAL-c584t-318ba5464a3f8afd903af52f1313f8f05fdc8b392384783458e6ca4fc8d4d7673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/gene.2013.19$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/gene.2013.19$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23615072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, W</creatorcontrib><creatorcontrib>Hui, K Y</creatorcontrib><creatorcontrib>Gusev, A</creatorcontrib><creatorcontrib>Warner, N</creatorcontrib><creatorcontrib>Ng, S M E</creatorcontrib><creatorcontrib>Ferguson, J</creatorcontrib><creatorcontrib>Choi, M</creatorcontrib><creatorcontrib>Burberry, A</creatorcontrib><creatorcontrib>Abraham, C</creatorcontrib><creatorcontrib>Mayer, L</creatorcontrib><creatorcontrib>Desnick, R J</creatorcontrib><creatorcontrib>Cardinale, C J</creatorcontrib><creatorcontrib>Hakonarson, H</creatorcontrib><creatorcontrib>Waterman, M</creatorcontrib><creatorcontrib>Chowers, Y</creatorcontrib><creatorcontrib>Karban, A</creatorcontrib><creatorcontrib>Brant, S R</creatorcontrib><creatorcontrib>Silverberg, M S</creatorcontrib><creatorcontrib>Gregersen, P K</creatorcontrib><creatorcontrib>Katz, S</creatorcontrib><creatorcontrib>Lifton, R P</creatorcontrib><creatorcontrib>Zhao, H</creatorcontrib><creatorcontrib>Nuñez, G</creatorcontrib><creatorcontrib>Pe'er, I</creatorcontrib><creatorcontrib>Peter, I</creatorcontrib><creatorcontrib>Cho, J H</creatorcontrib><title>Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at
NOD2
, in which three causal, uncommon and conditionally independent
NOD2
variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with
P
-value <10
−3
, respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in
TRPM2
on chromosome 21. Within the chromosome 16 region, R642S of
HEATR3
and rs9922362 of
BRD7
showed genome-wide significance. Expression studies of
HEATR3
demonstrated a positive role in NOD2-mediated NF-κB signaling. The
BRD7
signal showed conditional dependence with only the downstream rare CD-causal variants in
NOD2
, but not with the background haplotype; this elaborates
NOD2
as a key illustration of synthetic association.</description><subject>631/208/205</subject><subject>631/208/727/728</subject><subject>631/250/516/1909</subject><subject>692/699/249/2510/1402</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cellular signal transduction</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosome 16</subject><subject>Chromosome 21</subject><subject>Chromosomes, Human, Pair 16 - genetics</subject><subject>Crohn Disease - genetics</subject><subject>Crohn's disease</subject><subject>Demographic aspects</subject><subject>Development and progression</subject><subject>Etiology</subject><subject>Exons - genetics</subject><subject>Gene Expression</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>Haplotypes</subject><subject>HEK293 Cells</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunology</subject><subject>Jewish people</subject><subject>Jews - genetics</subject><subject>Logistic Models</subject><subject>Missense mutation</subject><subject>Mutation, Missense</subject><subject>NF-kappa B - genetics</subject><subject>NF-κB protein</subject><subject>NOD2</subject><subject>NOD2 protein</subject><subject>Nod2 Signaling Adaptor Protein - genetics</subject><subject>original-article</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Proteins - genetics</subject><subject>RNA Interference</subject><subject>Sequence Analysis, DNA</subject><subject>Signal Transduction - genetics</subject><subject>Transient receptor potential proteins</subject><issn>1466-4879</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNksFu1DAQhiMEoqVw44wscQFps9ix4ySXSstqS4sqkEo5W64z3rhk7RA7bZcTr4HEk_AQPARPgqMtLYt6QD7Ymvnm1_zjSZKnBE8JpuWrJViYZpjQKanuJbuEFTzNWYHvj2_OU1YW1U7yyPtzjAknvHqY7GSUkxwX2W7yfXEVwNZQo0Z2rQvrDpD03ikjg3EW-TDUa2Qsmveusb--fvOoNh6kB2RqsMFoAx5JZN0FtBM0880nsPKLQW_h0vgm9R2oyCi0Mt6DjWWrIWyko2hoAL07SH_-eI06GZpLuUajnQk6XMxOT-jj5IGWrYcn1_de8vFgcTo_TI_fvzmaz45TlZcspJSUZzJnnEmqS6nrClOp80wTSmJA41zXqjyjVUZLVpSU5SVwJZlWZc3qghd0L9nf6HbD2QpqFX31shVdb1ayXwsnjdjOWNOIpbsQtChzgvMo8OJaoHefB_BBRLsK2lZacIMXhJGKFpgS9j8oJTyveBbR5_-g527obZyEyDgjBeUFo7fUUrYgjNUutqhGUTGjjGQ8I7SK1PQOKp4aVkY5C9rE-FbBy62CyAS4Cks5eC-OPpxss5MNq3rnfQ_6ZnQEi3FJxfirYlxSQUb82d_jvoH_bGUE0g3gY8ouob81fqfgb1tI8pY</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Zhang, W</creator><creator>Hui, K Y</creator><creator>Gusev, A</creator><creator>Warner, N</creator><creator>Ng, S M E</creator><creator>Ferguson, J</creator><creator>Choi, M</creator><creator>Burberry, A</creator><creator>Abraham, C</creator><creator>Mayer, L</creator><creator>Desnick, R J</creator><creator>Cardinale, C J</creator><creator>Hakonarson, H</creator><creator>Waterman, M</creator><creator>Chowers, Y</creator><creator>Karban, A</creator><creator>Brant, S R</creator><creator>Silverberg, M S</creator><creator>Gregersen, P K</creator><creator>Katz, S</creator><creator>Lifton, R P</creator><creator>Zhao, H</creator><creator>Nuñez, G</creator><creator>Pe'er, I</creator><creator>Peter, I</creator><creator>Cho, J H</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130701</creationdate><title>Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3</title><author>Zhang, W ; Hui, K Y ; Gusev, A ; Warner, N ; Ng, S M E ; Ferguson, J ; Choi, M ; Burberry, A ; Abraham, C ; Mayer, L ; Desnick, R J ; Cardinale, C J ; Hakonarson, H ; Waterman, M ; Chowers, Y ; Karban, A ; Brant, S R ; Silverberg, M S ; Gregersen, P K ; Katz, S ; Lifton, R P ; Zhao, H ; Nuñez, G ; Pe'er, I ; Peter, I ; Cho, J H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-318ba5464a3f8afd903af52f1313f8f05fdc8b392384783458e6ca4fc8d4d7673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/208/205</topic><topic>631/208/727/728</topic><topic>631/250/516/1909</topic><topic>692/699/249/2510/1402</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cellular signal transduction</topic><topic>Chromosomal Proteins, Non-Histone - genetics</topic><topic>Chromosome 16</topic><topic>Chromosome 21</topic><topic>Chromosomes, Human, Pair 16 - genetics</topic><topic>Crohn Disease - genetics</topic><topic>Crohn's disease</topic><topic>Demographic aspects</topic><topic>Development and progression</topic><topic>Etiology</topic><topic>Exons - genetics</topic><topic>Gene Expression</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Genotyping</topic><topic>Haplotypes</topic><topic>HEK293 Cells</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunology</topic><topic>Jewish people</topic><topic>Jews - genetics</topic><topic>Logistic Models</topic><topic>Missense mutation</topic><topic>Mutation, Missense</topic><topic>NF-kappa B - genetics</topic><topic>NF-κB protein</topic><topic>NOD2</topic><topic>NOD2 protein</topic><topic>Nod2 Signaling Adaptor Protein - genetics</topic><topic>original-article</topic><topic>Physiological aspects</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Proteins - genetics</topic><topic>RNA Interference</topic><topic>Sequence Analysis, DNA</topic><topic>Signal Transduction - genetics</topic><topic>Transient receptor potential proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, W</creatorcontrib><creatorcontrib>Hui, K Y</creatorcontrib><creatorcontrib>Gusev, A</creatorcontrib><creatorcontrib>Warner, N</creatorcontrib><creatorcontrib>Ng, S M E</creatorcontrib><creatorcontrib>Ferguson, J</creatorcontrib><creatorcontrib>Choi, M</creatorcontrib><creatorcontrib>Burberry, A</creatorcontrib><creatorcontrib>Abraham, C</creatorcontrib><creatorcontrib>Mayer, L</creatorcontrib><creatorcontrib>Desnick, R J</creatorcontrib><creatorcontrib>Cardinale, C J</creatorcontrib><creatorcontrib>Hakonarson, H</creatorcontrib><creatorcontrib>Waterman, M</creatorcontrib><creatorcontrib>Chowers, Y</creatorcontrib><creatorcontrib>Karban, A</creatorcontrib><creatorcontrib>Brant, S R</creatorcontrib><creatorcontrib>Silverberg, M S</creatorcontrib><creatorcontrib>Gregersen, P K</creatorcontrib><creatorcontrib>Katz, S</creatorcontrib><creatorcontrib>Lifton, R P</creatorcontrib><creatorcontrib>Zhao, H</creatorcontrib><creatorcontrib>Nuñez, G</creatorcontrib><creatorcontrib>Pe'er, I</creatorcontrib><creatorcontrib>Peter, I</creatorcontrib><creatorcontrib>Cho, J H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, W</au><au>Hui, K Y</au><au>Gusev, A</au><au>Warner, N</au><au>Ng, S M E</au><au>Ferguson, J</au><au>Choi, M</au><au>Burberry, A</au><au>Abraham, C</au><au>Mayer, L</au><au>Desnick, R J</au><au>Cardinale, C J</au><au>Hakonarson, H</au><au>Waterman, M</au><au>Chowers, Y</au><au>Karban, A</au><au>Brant, S R</au><au>Silverberg, M S</au><au>Gregersen, P K</au><au>Katz, S</au><au>Lifton, R P</au><au>Zhao, H</au><au>Nuñez, G</au><au>Pe'er, I</au><au>Peter, I</au><au>Cho, J H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>14</volume><issue>5</issue><spage>310</spage><epage>316</epage><pages>310-316</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at
NOD2
, in which three causal, uncommon and conditionally independent
NOD2
variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with
P
-value <10
−3
, respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in
TRPM2
on chromosome 21. Within the chromosome 16 region, R642S of
HEATR3
and rs9922362 of
BRD7
showed genome-wide significance. Expression studies of
HEATR3
demonstrated a positive role in NOD2-mediated NF-κB signaling. The
BRD7
signal showed conditional dependence with only the downstream rare CD-causal variants in
NOD2
, but not with the background haplotype; this elaborates
NOD2
as a key illustration of synthetic association.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23615072</pmid><doi>10.1038/gene.2013.19</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1466-4879 |
| ispartof | Genes and immunity, 2013-07, Vol.14 (5), p.310-316 |
| issn | 1466-4879 1476-5470 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3785105 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | 631/208/205 631/208/727/728 631/250/516/1909 692/699/249/2510/1402 Biomedical and Life Sciences Biomedicine Cancer Research Cellular signal transduction Chromosomal Proteins, Non-Histone - genetics Chromosome 16 Chromosome 21 Chromosomes, Human, Pair 16 - genetics Crohn Disease - genetics Crohn's disease Demographic aspects Development and progression Etiology Exons - genetics Gene Expression Gene mutations Genetic aspects Genetic Predisposition to Disease - genetics Genome-Wide Association Study Genomes Genotype Genotyping Haplotypes HEK293 Cells Human Genetics Humans Immunology Jewish people Jews - genetics Logistic Models Missense mutation Mutation, Missense NF-kappa B - genetics NF-κB protein NOD2 NOD2 protein Nod2 Signaling Adaptor Protein - genetics original-article Physiological aspects Polymorphism, Single Nucleotide Population Proteins - genetics RNA Interference Sequence Analysis, DNA Signal Transduction - genetics Transient receptor potential proteins |
| title | Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T19%3A40%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Extended%20haplotype%20association%20study%20in%20Crohn%E2%80%99s%20disease%20identifies%20a%20novel,%20Ashkenazi%20Jewish-specific%20missense%20mutation%20in%20the%20NF-%CE%BAB%20pathway%20gene,%20HEATR3&rft.jtitle=Genes%20and%20immunity&rft.au=Zhang,%20W&rft.date=2013-07-01&rft.volume=14&rft.issue=5&rft.spage=310&rft.epage=316&rft.pages=310-316&rft.issn=1466-4879&rft.eissn=1476-5470&rft_id=info:doi/10.1038/gene.2013.19&rft_dat=%3Cgale_pubme%3EA341262139%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2641736743&rft_id=info:pmid/23615072&rft_galeid=A341262139&rfr_iscdi=true |