Co-regulation and multilocus determinants of gene expression in humans
Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expressio...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kerner, Berit [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2007 |
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| Schlagwörter: |
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| Anmerkung: |
© Kerner et al; licensee BioMed Central Ltd. 2007 |
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| Übergeordnetes Werk: |
Enthalten in: BMC proceedings - London : BioMed Central, 2007, 1(2007), Suppl 1 vom: 18. Dez. |
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| Übergeordnetes Werk: |
volume:1 ; year:2007 ; number:Suppl 1 ; day:18 ; month:12 |
| Links: |
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| DOI / URN: |
10.1186/1753-6561-1-S1-S88 |
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SPR028426886 |
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| 520 | |a Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. | ||
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| 700 | 1 | |a Cantor, Rita M |4 aut | |
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10.1186/1753-6561-1-S1-S88 doi (DE-627)SPR028426886 (SPR)1753-6561-1-S1-S88-e DE-627 ger DE-627 rakwb eng Kerner, Berit verfasserin aut Co-regulation and multilocus determinants of gene expression in humans 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Kerner et al; licensee BioMed Central Ltd. 2007 Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. Stepwise Regression (dpeaa)DE-He213 Expression Trait (dpeaa)DE-He213 Multiple SNPs (dpeaa)DE-He213 Mendelian Error (dpeaa)DE-He213 Solar Software (dpeaa)DE-He213 Bailey, Julia N aut Cantor, Rita M aut Enthalten in BMC proceedings London : BioMed Central, 2007 1(2007), Suppl 1 vom: 18. Dez. (DE-627)559080840 (DE-600)2411867-9 1753-6561 nnns volume:1 year:2007 number:Suppl 1 day:18 month:12 https://dx.doi.org/10.1186/1753-6561-1-S1-S88 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 1 2007 Suppl 1 18 12 |
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10.1186/1753-6561-1-S1-S88 doi (DE-627)SPR028426886 (SPR)1753-6561-1-S1-S88-e DE-627 ger DE-627 rakwb eng Kerner, Berit verfasserin aut Co-regulation and multilocus determinants of gene expression in humans 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Kerner et al; licensee BioMed Central Ltd. 2007 Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. Stepwise Regression (dpeaa)DE-He213 Expression Trait (dpeaa)DE-He213 Multiple SNPs (dpeaa)DE-He213 Mendelian Error (dpeaa)DE-He213 Solar Software (dpeaa)DE-He213 Bailey, Julia N aut Cantor, Rita M aut Enthalten in BMC proceedings London : BioMed Central, 2007 1(2007), Suppl 1 vom: 18. Dez. (DE-627)559080840 (DE-600)2411867-9 1753-6561 nnns volume:1 year:2007 number:Suppl 1 day:18 month:12 https://dx.doi.org/10.1186/1753-6561-1-S1-S88 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 1 2007 Suppl 1 18 12 |
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10.1186/1753-6561-1-S1-S88 doi (DE-627)SPR028426886 (SPR)1753-6561-1-S1-S88-e DE-627 ger DE-627 rakwb eng Kerner, Berit verfasserin aut Co-regulation and multilocus determinants of gene expression in humans 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Kerner et al; licensee BioMed Central Ltd. 2007 Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. Stepwise Regression (dpeaa)DE-He213 Expression Trait (dpeaa)DE-He213 Multiple SNPs (dpeaa)DE-He213 Mendelian Error (dpeaa)DE-He213 Solar Software (dpeaa)DE-He213 Bailey, Julia N aut Cantor, Rita M aut Enthalten in BMC proceedings London : BioMed Central, 2007 1(2007), Suppl 1 vom: 18. Dez. (DE-627)559080840 (DE-600)2411867-9 1753-6561 nnns volume:1 year:2007 number:Suppl 1 day:18 month:12 https://dx.doi.org/10.1186/1753-6561-1-S1-S88 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 1 2007 Suppl 1 18 12 |
| allfieldsGer |
10.1186/1753-6561-1-S1-S88 doi (DE-627)SPR028426886 (SPR)1753-6561-1-S1-S88-e DE-627 ger DE-627 rakwb eng Kerner, Berit verfasserin aut Co-regulation and multilocus determinants of gene expression in humans 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Kerner et al; licensee BioMed Central Ltd. 2007 Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. Stepwise Regression (dpeaa)DE-He213 Expression Trait (dpeaa)DE-He213 Multiple SNPs (dpeaa)DE-He213 Mendelian Error (dpeaa)DE-He213 Solar Software (dpeaa)DE-He213 Bailey, Julia N aut Cantor, Rita M aut Enthalten in BMC proceedings London : BioMed Central, 2007 1(2007), Suppl 1 vom: 18. Dez. (DE-627)559080840 (DE-600)2411867-9 1753-6561 nnns volume:1 year:2007 number:Suppl 1 day:18 month:12 https://dx.doi.org/10.1186/1753-6561-1-S1-S88 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 1 2007 Suppl 1 18 12 |
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10.1186/1753-6561-1-S1-S88 doi (DE-627)SPR028426886 (SPR)1753-6561-1-S1-S88-e DE-627 ger DE-627 rakwb eng Kerner, Berit verfasserin aut Co-regulation and multilocus determinants of gene expression in humans 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Kerner et al; licensee BioMed Central Ltd. 2007 Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. Stepwise Regression (dpeaa)DE-He213 Expression Trait (dpeaa)DE-He213 Multiple SNPs (dpeaa)DE-He213 Mendelian Error (dpeaa)DE-He213 Solar Software (dpeaa)DE-He213 Bailey, Julia N aut Cantor, Rita M aut Enthalten in BMC proceedings London : BioMed Central, 2007 1(2007), Suppl 1 vom: 18. Dez. (DE-627)559080840 (DE-600)2411867-9 1753-6561 nnns volume:1 year:2007 number:Suppl 1 day:18 month:12 https://dx.doi.org/10.1186/1753-6561-1-S1-S88 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 1 2007 Suppl 1 18 12 |
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On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. 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co-regulation and multilocus determinants of gene expression in humans |
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Co-regulation and multilocus determinants of gene expression in humans |
| abstract |
Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. © Kerner et al; licensee BioMed Central Ltd. 2007 |
| abstractGer |
Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. © Kerner et al; licensee BioMed Central Ltd. 2007 |
| abstract_unstemmed |
Background The regulation of gene expression is an emerging area of investigation. Increased knowledge can deepen our understanding of the genetic contributions to variations in complex traits. The purpose of this study is to explore the feasibility of detecting regulatory elements of gene expression with multivariate analyses. Methods Peripheral blood lymphocyte expression levels of 30 genes on chromosome 5 and a single gene, DEAD, on chromosome 22 were analyzed in single-point variance-component linkage analyses in multiplex families to identify putative regulatory regions. To explore the possibility of regulatory regions having individual relationships with the expression levels of a single gene, we utilized stepwise regression. To explore the possibility of pleiotropy of a single regulatory locus for multiple genes, bivariate linkage analysis was applied. Results Twenty-one loci were linked to five expression levels. The two most significant were for the known region on chromosome 22 (LOD = 4.62). On chromosome 5 a LOD of 4.57 was found for the gene leukocyte-derived arginine aminopeptidase (LRAP) with a single-nucleotide polymorphism (SNP) within 5 Mb. Both genes showed evidence of linkage to multiple SNPs. When 194 family members were treated as independent, stepwise regression identified fewer single-nucleotide polymorphisms with significant predictive values (p < 0.05), providing evidence for multiple regulatory regions of unequal effect. However, when corrections for non-independence were applied these results could no longer be detected. Conclusion The complex nature of gene regulation can be explored by linkage analysis with single-nucleotide polymorphisms followed by multivariate methods to explore co-regulation. © Kerner et al; licensee BioMed Central Ltd. 2007 |
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| score |
7.398878 |