Abstract
Recently, gene expression levels have been shown to demonstrate familial aggregation, suggesting a direct role of heritable DNA variation. We studied the gene expression levels in lymphoblastoid cells of the Centre d'Etude du Polymorphisme Humain Utah families made available to Genetic Analysis Workshop 15 (GAW15), using genome-wide linkage analyses. Heritability was estimated for the expression levels of each individual phenotype. Genome wide linkage analysis was then performed using the 2819 SNPs for the expression levels of all the genes. Heritability exceeded 0.21 for 50% of the expressed phenotypes. Genome-wide linkage analysis demonstrated that 19 of them reached significance after correcting for multiple comparisons, only 4 of which were reported previously. We did not identify any hot spots of transcriptional regulation when assuming LOD score > 5.3 for significant linkage evidence. Our analysis suggests that inconsistent results in comparison to the previous report may be due to the different approaches, phenotype transformation, and different pedigree data used in the analyses.
Highlights
Gene expression levels have been shown to demonstrate familial aggregation, suggesting a direct role of heritable DNA variation
Genetic diseases are the ultimate manifestation of pathological genetic variation, under some circumstances they may reflect the influence of environmental factors
We studied the same expression data made available to Genetic Analysis Workshop 15 (GAW15), using the variance-components method implemented in Merlin [3] in order to compare to the results obtained in the original report obtained with SIBPAL in S.A.G.E. [4]
Summary
Gene expression levels have been shown to demonstrate familial aggregation, suggesting a direct role of heritable DNA variation. We studied the gene expression levels in lymphoblastoid cells of the Centre d'Etude du Polymorphisme Humain Utah families made available to Genetic Analysis Workshop 15 (GAW15), using genome-wide linkage analyses. Cheung et al [1] studied variation in human gene expression across the genome by comparing variation among unrelated individuals, among siblings within families, and between monozygotic twins. They found significant evidence for familial aggregation of gene expression phenotypes, suggesting a contribution from germ line genetic variation. BMC Proceedings 2007, 1(Suppl 1):S87 http://www.biomedcentral.com/1753-6561/1/S1/S87 phisms (SNPs) They identified significant linkage evidence for a large proportion of the expression phenotypes, further supporting a role for DNA sequence variation on these phenotypes. The rationale for this comparison is that the variance-components approach may be more powerful than SIBPAL when a phenotype is normally distributed, but SIBPAL is robust to the normality assumption, the variance-components approach is not
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