Genetic analysis of genome-wide variation in human gene expression

Genetic analysis of genome-wide variation in human gene expression

2004 August 12; 430(7001): 743–747 | Michael Morley, Cliona M. Molony, Teresa M. Weber, James L. Devlin, Kathryn G. Ewens, Richard S. Spielman, Vivian G. Cheung
The study investigates the genetic determinants of gene expression variation in humans using microarrays and genome-wide linkage analysis. The researchers analyzed gene expression levels in 3,554 genes from 14 large families, identifying significant linkage to specific chromosomal regions for approximately 1,000 expression phenotypes. Both cis- and trans-acting loci regulate gene expression levels, with most acting in trans. The analysis revealed hotspots of transcriptional regulation where multiple expression phenotypes show significant linkage, suggesting shared regulatory regions. The study also found that many gene expression phenotypes are influenced by multiple genetic determinants. The combination of microarray techniques for phenotyping and linkage analysis for quantitative traits allows for the genetic mapping of determinants contributing to human gene expression variation. The results highlight the importance of understanding the genetic basis of gene expression in human biology and disease susceptibility.The study investigates the genetic determinants of gene expression variation in humans using microarrays and genome-wide linkage analysis. The researchers analyzed gene expression levels in 3,554 genes from 14 large families, identifying significant linkage to specific chromosomal regions for approximately 1,000 expression phenotypes. Both cis- and trans-acting loci regulate gene expression levels, with most acting in trans. The analysis revealed hotspots of transcriptional regulation where multiple expression phenotypes show significant linkage, suggesting shared regulatory regions. The study also found that many gene expression phenotypes are influenced by multiple genetic determinants. The combination of microarray techniques for phenotyping and linkage analysis for quantitative traits allows for the genetic mapping of determinants contributing to human gene expression variation. The results highlight the importance of understanding the genetic basis of gene expression in human biology and disease susceptibility.
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