Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci
Genome-wide linkage scans to identify asthma susceptibility loci have revealed many linked regions, including a broad region on chromosome 5p. To identify a 5p-linked asthma or bronchial hyperresponsiveness (BHR) locus. We performed fine mapping and positional candidate studies of this region in the...
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| creator | Kurz, Thorsten Hoffjan, Sabine Hayes, M. Geoffrey Schneider, Dan Nicolae, Raluca Heinzmann, Andrea Jerkic, Sylvija P. Parry, Rod Cox, Nancy J. Deichmann, Klaus A. Ober, Carole |
| description | Genome-wide linkage scans to identify asthma susceptibility loci have revealed many linked regions, including a broad region on chromosome 5p.
To identify a 5p-linked asthma or bronchial hyperresponsiveness (BHR) locus.
We performed fine mapping and positional candidate studies of this region in the Hutterites and an outbred case-control sample from Germany by genotyping 89 single nucleotide polymorphisms (SNPs) in 22 genes. SNP and haplotype analyses were performed.
Three genes in a distal region (zinc finger RNA binding protein [
ZFR], natriuretic peptide receptor C, and a disintegrin and metalloproteinase domain with thrombospondin type 1 motif [
ADAMTS12]) were associated with BHR, whereas 4 genes in a proximal region (prolactin receptor, IL-7 receptor [
IL7R], leukemia inhibitory factor receptor [
LIFR], and prostaglandin E4 receptor [
PTGER4]) were associated with asthma symptoms in the Hutterites. Furthermore, nearly the entire original linkage signal in the Hutterites was generated by individuals who had the risk-associated alleles in
ZFR3, natriuretic peptide receptor C,
ADAMTS12,
LIFR, and
PTGER4. Variation in
ADAMTS12, IL7R, and
PTGER4 were also associated with asthma in the outbred Germans, and the frequencies of long-range haplotypes composed of SNPs at
ZFR,
ADAMTS12,
IL7R,
LIFR, and
PTGER4 were significantly different between both the German and Hutterite cases and controls. There is little linkage disequilbrium between alleles in these 2 regions in either population.
These results suggest that a broad region on 5p, separated by >9 Mb, harbors at least 2 and possibly 5 asthma or BHR susceptibility loci. These findings are consistent with the hypothesis that regions providing evidence for linkage in multiple populations may, in fact, house more than 1 susceptibility locus, as appears to be the case for the linked region on 5p.
Identifying asthma or BHR genes could lead to novel therapeutic approaches. |
| doi_str_mv | 10.1016/j.jaci.2006.04.036 |
| format | Article |
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To identify a 5p-linked asthma or bronchial hyperresponsiveness (BHR) locus.
We performed fine mapping and positional candidate studies of this region in the Hutterites and an outbred case-control sample from Germany by genotyping 89 single nucleotide polymorphisms (SNPs) in 22 genes. SNP and haplotype analyses were performed.
Three genes in a distal region (zinc finger RNA binding protein [
ZFR], natriuretic peptide receptor C, and a disintegrin and metalloproteinase domain with thrombospondin type 1 motif [
ADAMTS12]) were associated with BHR, whereas 4 genes in a proximal region (prolactin receptor, IL-7 receptor [
IL7R], leukemia inhibitory factor receptor [
LIFR], and prostaglandin E4 receptor [
PTGER4]) were associated with asthma symptoms in the Hutterites. Furthermore, nearly the entire original linkage signal in the Hutterites was generated by individuals who had the risk-associated alleles in
ZFR3, natriuretic peptide receptor C,
ADAMTS12,
LIFR, and
PTGER4. Variation in
ADAMTS12, IL7R, and
PTGER4 were also associated with asthma in the outbred Germans, and the frequencies of long-range haplotypes composed of SNPs at
ZFR,
ADAMTS12,
IL7R,
LIFR, and
PTGER4 were significantly different between both the German and Hutterite cases and controls. There is little linkage disequilbrium between alleles in these 2 regions in either population.
These results suggest that a broad region on 5p, separated by >9 Mb, harbors at least 2 and possibly 5 asthma or BHR susceptibility loci. These findings are consistent with the hypothesis that regions providing evidence for linkage in multiple populations may, in fact, house more than 1 susceptibility locus, as appears to be the case for the linked region on 5p.
Identifying asthma or BHR genes could lead to novel therapeutic approaches.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2006.04.036</identifier><identifier>PMID: 16890764</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Asthma ; Asthma - epidemiology ; Asthma - genetics ; Biological and medical sciences ; Candidates ; Case-Control Studies ; Chromosome Mapping ; Chromosomes ; Chromosomes, Human, Pair 5 ; Disease ; Family medical history ; founder population ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genes ; Genetic Predisposition to Disease ; Genomes ; Genomics ; Germany - epidemiology ; Humans ; Immunopathology ; Leukemia ; linkage ; Medical sciences ; Pathogenesis ; Polymorphism, Single Nucleotide ; Studies</subject><ispartof>Journal of allergy and clinical immunology, 2006-08, Vol.118 (2), p.396-402</ispartof><rights>2006 American Academy of Allergy, Asthma and Immunology</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Elsevier Limited Aug 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-420cb7058eae3a269ebe1acbefc5e5e9a946c4aca04b4fd58b4f60688ad3f5743</citedby><cites>FETCH-LOGICAL-c478t-420cb7058eae3a269ebe1acbefc5e5e9a946c4aca04b4fd58b4f60688ad3f5743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaci.2006.04.036$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18028067$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16890764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kurz, Thorsten</creatorcontrib><creatorcontrib>Hoffjan, Sabine</creatorcontrib><creatorcontrib>Hayes, M. Geoffrey</creatorcontrib><creatorcontrib>Schneider, Dan</creatorcontrib><creatorcontrib>Nicolae, Raluca</creatorcontrib><creatorcontrib>Heinzmann, Andrea</creatorcontrib><creatorcontrib>Jerkic, Sylvija P.</creatorcontrib><creatorcontrib>Parry, Rod</creatorcontrib><creatorcontrib>Cox, Nancy J.</creatorcontrib><creatorcontrib>Deichmann, Klaus A.</creatorcontrib><creatorcontrib>Ober, Carole</creatorcontrib><title>Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Genome-wide linkage scans to identify asthma susceptibility loci have revealed many linked regions, including a broad region on chromosome 5p.
To identify a 5p-linked asthma or bronchial hyperresponsiveness (BHR) locus.
We performed fine mapping and positional candidate studies of this region in the Hutterites and an outbred case-control sample from Germany by genotyping 89 single nucleotide polymorphisms (SNPs) in 22 genes. SNP and haplotype analyses were performed.
Three genes in a distal region (zinc finger RNA binding protein [
ZFR], natriuretic peptide receptor C, and a disintegrin and metalloproteinase domain with thrombospondin type 1 motif [
ADAMTS12]) were associated with BHR, whereas 4 genes in a proximal region (prolactin receptor, IL-7 receptor [
IL7R], leukemia inhibitory factor receptor [
LIFR], and prostaglandin E4 receptor [
PTGER4]) were associated with asthma symptoms in the Hutterites. Furthermore, nearly the entire original linkage signal in the Hutterites was generated by individuals who had the risk-associated alleles in
ZFR3, natriuretic peptide receptor C,
ADAMTS12,
LIFR, and
PTGER4. Variation in
ADAMTS12, IL7R, and
PTGER4 were also associated with asthma in the outbred Germans, and the frequencies of long-range haplotypes composed of SNPs at
ZFR,
ADAMTS12,
IL7R,
LIFR, and
PTGER4 were significantly different between both the German and Hutterite cases and controls. There is little linkage disequilbrium between alleles in these 2 regions in either population.
These results suggest that a broad region on 5p, separated by >9 Mb, harbors at least 2 and possibly 5 asthma or BHR susceptibility loci. These findings are consistent with the hypothesis that regions providing evidence for linkage in multiple populations may, in fact, house more than 1 susceptibility locus, as appears to be the case for the linked region on 5p.
Identifying asthma or BHR genes could lead to novel therapeutic approaches.</description><subject>Asthma</subject><subject>Asthma - epidemiology</subject><subject>Asthma - genetics</subject><subject>Biological and medical sciences</subject><subject>Candidates</subject><subject>Case-Control Studies</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 5</subject><subject>Disease</subject><subject>Family medical history</subject><subject>founder population</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genes</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Germany - epidemiology</subject><subject>Humans</subject><subject>Immunopathology</subject><subject>Leukemia</subject><subject>linkage</subject><subject>Medical sciences</subject><subject>Pathogenesis</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Studies</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGL1TAQxoMo7nP1H_AgAdFb66RN0xS8yOLuCgte9BzSdOpOaZuapML7783jPVjw4GWGgd83zHwfY28FlAKE-jSVk3VUVgCqBFlCrZ6xg4CuLZSumufsANCJQrWyu2KvYpwgz7XuXrIroXQHrZIHttzSinyx20brL27XgW8-UiK_2pm7PNNgE_KY9oEwcr9y9xj84qNfkDebqDkNuCYaj3zZ50TbjNzG9LhYHvfocEvU00zpyGfv6DV7Mdo54ptLv2Y_b7_-uLkvHr7ffbv58lA42epUyApc30Kj0WJtK9Vhj8K6HkfXYIOd7aRy0joLspfj0OhcFSit7VCPTSvra_bxvHcL_veOMZmF8jHzbFf0ezRKt9kCDRl8_w84-T3k36MRDci2ER1UmarOlAs-xoCj2QItNhyNAHOKwkzmFIU5RWFAmhxFFr27rN77BYcnycX7DHy4ADY6O4_Bro7iE6eh0qDazH0-c5gd-0MYTHSEq8OBArpkBk__u-MvGC6pEQ</recordid><startdate>20060801</startdate><enddate>20060801</enddate><creator>Kurz, Thorsten</creator><creator>Hoffjan, Sabine</creator><creator>Hayes, M. Geoffrey</creator><creator>Schneider, Dan</creator><creator>Nicolae, Raluca</creator><creator>Heinzmann, Andrea</creator><creator>Jerkic, Sylvija P.</creator><creator>Parry, Rod</creator><creator>Cox, Nancy J.</creator><creator>Deichmann, Klaus A.</creator><creator>Ober, Carole</creator><general>Mosby, Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><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>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20060801</creationdate><title>Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci</title><author>Kurz, Thorsten ; Hoffjan, Sabine ; Hayes, M. Geoffrey ; Schneider, Dan ; Nicolae, Raluca ; Heinzmann, Andrea ; Jerkic, Sylvija P. ; Parry, Rod ; Cox, Nancy J. ; Deichmann, Klaus A. ; Ober, Carole</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-420cb7058eae3a269ebe1acbefc5e5e9a946c4aca04b4fd58b4f60688ad3f5743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Asthma</topic><topic>Asthma - epidemiology</topic><topic>Asthma - genetics</topic><topic>Biological and medical sciences</topic><topic>Candidates</topic><topic>Case-Control Studies</topic><topic>Chromosome Mapping</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 5</topic><topic>Disease</topic><topic>Family medical history</topic><topic>founder population</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Genes</topic><topic>Genetic Predisposition to Disease</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Germany - epidemiology</topic><topic>Humans</topic><topic>Immunopathology</topic><topic>Leukemia</topic><topic>linkage</topic><topic>Medical sciences</topic><topic>Pathogenesis</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kurz, Thorsten</creatorcontrib><creatorcontrib>Hoffjan, Sabine</creatorcontrib><creatorcontrib>Hayes, M. Geoffrey</creatorcontrib><creatorcontrib>Schneider, Dan</creatorcontrib><creatorcontrib>Nicolae, Raluca</creatorcontrib><creatorcontrib>Heinzmann, Andrea</creatorcontrib><creatorcontrib>Jerkic, Sylvija P.</creatorcontrib><creatorcontrib>Parry, Rod</creatorcontrib><creatorcontrib>Cox, Nancy J.</creatorcontrib><creatorcontrib>Deichmann, Klaus A.</creatorcontrib><creatorcontrib>Ober, Carole</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kurz, Thorsten</au><au>Hoffjan, Sabine</au><au>Hayes, M. Geoffrey</au><au>Schneider, Dan</au><au>Nicolae, Raluca</au><au>Heinzmann, Andrea</au><au>Jerkic, Sylvija P.</au><au>Parry, Rod</au><au>Cox, Nancy J.</au><au>Deichmann, Klaus A.</au><au>Ober, Carole</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2006-08-01</date><risdate>2006</risdate><volume>118</volume><issue>2</issue><spage>396</spage><epage>402</epage><pages>396-402</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><coden>JACIBY</coden><abstract>Genome-wide linkage scans to identify asthma susceptibility loci have revealed many linked regions, including a broad region on chromosome 5p.
To identify a 5p-linked asthma or bronchial hyperresponsiveness (BHR) locus.
We performed fine mapping and positional candidate studies of this region in the Hutterites and an outbred case-control sample from Germany by genotyping 89 single nucleotide polymorphisms (SNPs) in 22 genes. SNP and haplotype analyses were performed.
Three genes in a distal region (zinc finger RNA binding protein [
ZFR], natriuretic peptide receptor C, and a disintegrin and metalloproteinase domain with thrombospondin type 1 motif [
ADAMTS12]) were associated with BHR, whereas 4 genes in a proximal region (prolactin receptor, IL-7 receptor [
IL7R], leukemia inhibitory factor receptor [
LIFR], and prostaglandin E4 receptor [
PTGER4]) were associated with asthma symptoms in the Hutterites. Furthermore, nearly the entire original linkage signal in the Hutterites was generated by individuals who had the risk-associated alleles in
ZFR3, natriuretic peptide receptor C,
ADAMTS12,
LIFR, and
PTGER4. Variation in
ADAMTS12, IL7R, and
PTGER4 were also associated with asthma in the outbred Germans, and the frequencies of long-range haplotypes composed of SNPs at
ZFR,
ADAMTS12,
IL7R,
LIFR, and
PTGER4 were significantly different between both the German and Hutterite cases and controls. There is little linkage disequilbrium between alleles in these 2 regions in either population.
These results suggest that a broad region on 5p, separated by >9 Mb, harbors at least 2 and possibly 5 asthma or BHR susceptibility loci. These findings are consistent with the hypothesis that regions providing evidence for linkage in multiple populations may, in fact, house more than 1 susceptibility locus, as appears to be the case for the linked region on 5p.
Identifying asthma or BHR genes could lead to novel therapeutic approaches.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>16890764</pmid><doi>10.1016/j.jaci.2006.04.036</doi><tpages>7</tpages></addata></record> |
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| ispartof | Journal of allergy and clinical immunology, 2006-08, Vol.118 (2), p.396-402 |
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| source | MEDLINE; ScienceDirect Freedom Collection (Elsevier); EZB Electronic Journals Library |
| subjects | Asthma Asthma - epidemiology Asthma - genetics Biological and medical sciences Candidates Case-Control Studies Chromosome Mapping Chromosomes Chromosomes, Human, Pair 5 Disease Family medical history founder population Fundamental and applied biological sciences. Psychology Fundamental immunology Genes Genetic Predisposition to Disease Genomes Genomics Germany - epidemiology Humans Immunopathology Leukemia linkage Medical sciences Pathogenesis Polymorphism, Single Nucleotide Studies |
| title | Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci |
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