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Expression differences by continent of origin point to the immortalization process.

Davis AR, Kohane IS - Hum. Mol. Genet. (2009)

Bottom Line: Analysis of recently available microarray expression data sets obtained from immortalized cell lines of the individuals represented in the HapMap project have led to inconclusive comparisons across cohorts with different ancestral continent of origin (ACOO).We further demonstrate that these differences correlate with viral titer and that both the titer and expression differences are associated with ACOO.We use the 14 genes most differentially expressed to construct an ACOO-specific 'immortalization network' comprised of 40 genes, one of which show significant correlation with genomic variation (eQTL).

View Article: PubMed Central - PubMed

Affiliation: i2b2 National Center for Biomedical Computing, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. ardavis@partners.org

ABSTRACT
Analysis of recently available microarray expression data sets obtained from immortalized cell lines of the individuals represented in the HapMap project have led to inconclusive comparisons across cohorts with different ancestral continent of origin (ACOO). To address this apparent inconsistency, we applied a novel approach to accentuate population-specific gene expression signatures for the CEU [homogeneous US residents with northern and western European ancestry (HapMap samples)] and YRI [homogenous Yoruba people of Ibadan, Nigeria (HapMap samples)] trios. In this report, we describe how four independent data sets point to the differential expression across ACOO of gene networks implicated in transforming the normal lymphoblast into immortalized lymphoblastoid cells. In particular, Werner syndrome helicase and related genes are differentially expressed between the YRI and CEU cohorts. We further demonstrate that these differences correlate with viral titer and that both the titer and expression differences are associated with ACOO. We use the 14 genes most differentially expressed to construct an ACOO-specific 'immortalization network' comprised of 40 genes, one of which show significant correlation with genomic variation (eQTL). The extent to which these measured group differences are due to differences in the immortalization procedures used for each group or reflect ACOO-specific biological differences remains to be determined. That the ACOO group differences in gene expression patterns may depend strongly on the process of transforming cells to establish immortalized lines should be considered in such comparisons.

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Twelve of the 14 probe sets identified in the Venn diagram with immortalized cell-specific differential expression (circled in Venn diagram), mapped to 12 independent genes in Ingenuity Pathway program to construct the ‘immortalization network'. The 12 independent genes are depicted in red. POLR1A which has an heritable eQTL in the YRI population with significant differential expression by ACOO is in green. The additional genes with ACOO significantly different expression but are not immortalization specific are in yellow.
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DDP330F4: Twelve of the 14 probe sets identified in the Venn diagram with immortalized cell-specific differential expression (circled in Venn diagram), mapped to 12 independent genes in Ingenuity Pathway program to construct the ‘immortalization network'. The 12 independent genes are depicted in red. POLR1A which has an heritable eQTL in the YRI population with significant differential expression by ACOO is in green. The additional genes with ACOO significantly different expression but are not immortalization specific are in yellow.

Mentions: To further explore which subset of the COO differentially expressed genes is specific to ACOO but not immortalization and specific to differences in the immortalization process with respect to ACOO, the results above were contrasted to an expression study of non-immortalized lymphoid cells harvested from the peripheral blood from AA and CA children. Figure 4 depicts a Venn diagram of the 78 significantly differentially expressed probe sets across platforms (Illumina and Affymetrix) between the immortalized CEU/YRI cells. Of those, 64 probe sets (82%) were confirmed to be significantly different between the AA and CA children populations. This left 14 probe sets (including WRN) that were differentially expressed across the CEU and YRI in the immortalized cell experiments.


Expression differences by continent of origin point to the immortalization process.

Davis AR, Kohane IS - Hum. Mol. Genet. (2009)

Twelve of the 14 probe sets identified in the Venn diagram with immortalized cell-specific differential expression (circled in Venn diagram), mapped to 12 independent genes in Ingenuity Pathway program to construct the ‘immortalization network'. The 12 independent genes are depicted in red. POLR1A which has an heritable eQTL in the YRI population with significant differential expression by ACOO is in green. The additional genes with ACOO significantly different expression but are not immortalization specific are in yellow.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2748894&req=5

DDP330F4: Twelve of the 14 probe sets identified in the Venn diagram with immortalized cell-specific differential expression (circled in Venn diagram), mapped to 12 independent genes in Ingenuity Pathway program to construct the ‘immortalization network'. The 12 independent genes are depicted in red. POLR1A which has an heritable eQTL in the YRI population with significant differential expression by ACOO is in green. The additional genes with ACOO significantly different expression but are not immortalization specific are in yellow.
Mentions: To further explore which subset of the COO differentially expressed genes is specific to ACOO but not immortalization and specific to differences in the immortalization process with respect to ACOO, the results above were contrasted to an expression study of non-immortalized lymphoid cells harvested from the peripheral blood from AA and CA children. Figure 4 depicts a Venn diagram of the 78 significantly differentially expressed probe sets across platforms (Illumina and Affymetrix) between the immortalized CEU/YRI cells. Of those, 64 probe sets (82%) were confirmed to be significantly different between the AA and CA children populations. This left 14 probe sets (including WRN) that were differentially expressed across the CEU and YRI in the immortalized cell experiments.

Bottom Line: Analysis of recently available microarray expression data sets obtained from immortalized cell lines of the individuals represented in the HapMap project have led to inconclusive comparisons across cohorts with different ancestral continent of origin (ACOO).We further demonstrate that these differences correlate with viral titer and that both the titer and expression differences are associated with ACOO.We use the 14 genes most differentially expressed to construct an ACOO-specific 'immortalization network' comprised of 40 genes, one of which show significant correlation with genomic variation (eQTL).

View Article: PubMed Central - PubMed

Affiliation: i2b2 National Center for Biomedical Computing, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. ardavis@partners.org

ABSTRACT
Analysis of recently available microarray expression data sets obtained from immortalized cell lines of the individuals represented in the HapMap project have led to inconclusive comparisons across cohorts with different ancestral continent of origin (ACOO). To address this apparent inconsistency, we applied a novel approach to accentuate population-specific gene expression signatures for the CEU [homogeneous US residents with northern and western European ancestry (HapMap samples)] and YRI [homogenous Yoruba people of Ibadan, Nigeria (HapMap samples)] trios. In this report, we describe how four independent data sets point to the differential expression across ACOO of gene networks implicated in transforming the normal lymphoblast into immortalized lymphoblastoid cells. In particular, Werner syndrome helicase and related genes are differentially expressed between the YRI and CEU cohorts. We further demonstrate that these differences correlate with viral titer and that both the titer and expression differences are associated with ACOO. We use the 14 genes most differentially expressed to construct an ACOO-specific 'immortalization network' comprised of 40 genes, one of which show significant correlation with genomic variation (eQTL). The extent to which these measured group differences are due to differences in the immortalization procedures used for each group or reflect ACOO-specific biological differences remains to be determined. That the ACOO group differences in gene expression patterns may depend strongly on the process of transforming cells to establish immortalized lines should be considered in such comparisons.

Show MeSH
Related in: MedlinePlus