This study investigates genetic factors influencing gene expression variation in humans. Using microarray technology and genome-wide linkage analysis, researchers examined 3,554 genes in 14 large families to identify genetic determinants of gene expression levels. They found significant evidence of linkage for approximately 1,000 expression phenotypes, with many genes showing correlated expression levels influenced by shared regulatory regions. The study identified hotspots of transcriptional regulation where multiple expression phenotypes showed significant linkage, suggesting the presence of master regulators affecting gene expression. The analysis distinguished between cis- and trans-acting regulators. Cis-acting regulators are located near the target gene, while trans-acting regulators influence gene expression from distant locations. The study found that most expression phenotypes are influenced by trans-acting regulators, although some are influenced by cis-acting regulators. The results suggest that many genes are regulated by shared regulatory regions, with some genes showing strong correlations in expression levels. The study also identified differential allelic expression, where one allele of a gene is expressed more than the other. This was observed in several genes, with significant evidence of linkage between SNPs and gene expression levels. The results suggest that genetic factors influence gene expression variation, and that these factors can be mapped using genome-wide linkage analysis. The study highlights the importance of genetic factors in gene expression variation and provides evidence that gene expression is influenced by both cis- and trans-acting regulators. The findings suggest that understanding the genetic basis of gene expression variation can provide insights into the genetic architecture of complex traits and diseases. The study also demonstrates the utility of genome-wide linkage analysis in identifying genetic determinants of gene expression.This study investigates genetic factors influencing gene expression variation in humans. Using microarray technology and genome-wide linkage analysis, researchers examined 3,554 genes in 14 large families to identify genetic determinants of gene expression levels. They found significant evidence of linkage for approximately 1,000 expression phenotypes, with many genes showing correlated expression levels influenced by shared regulatory regions. The study identified hotspots of transcriptional regulation where multiple expression phenotypes showed significant linkage, suggesting the presence of master regulators affecting gene expression. The analysis distinguished between cis- and trans-acting regulators. Cis-acting regulators are located near the target gene, while trans-acting regulators influence gene expression from distant locations. The study found that most expression phenotypes are influenced by trans-acting regulators, although some are influenced by cis-acting regulators. The results suggest that many genes are regulated by shared regulatory regions, with some genes showing strong correlations in expression levels. The study also identified differential allelic expression, where one allele of a gene is expressed more than the other. This was observed in several genes, with significant evidence of linkage between SNPs and gene expression levels. The results suggest that genetic factors influence gene expression variation, and that these factors can be mapped using genome-wide linkage analysis. The study highlights the importance of genetic factors in gene expression variation and provides evidence that gene expression is influenced by both cis- and trans-acting regulators. The findings suggest that understanding the genetic basis of gene expression variation can provide insights into the genetic architecture of complex traits and diseases. The study also demonstrates the utility of genome-wide linkage analysis in identifying genetic determinants of gene expression.