一种大规模绘制基因图谱的新颖方法,被用来显示一组其表达在人类B细胞中似乎是受遗传控制的基因,同时用来绘制控制这些基因表达的因子的图谱。通过将微阵列方法和定量特性分析方法结合起来,研究人员找到了控制1000个以上基因的表达的染色体位点以及引起其自然变异的复杂的转录调节网络。该方法有可能用在对疾病来说重要的组织中,帮助识别复杂疾病的遗传病因。
Genetic analysis of genome-wide variation in human gene expression
MICHAEL MORLEY1,3,*, CLIONA M. MOLONY2,*, TERESA M. WEBER1,3, JAMES L. DEVLIN2, KATHRYN G. EWENS2, RICHARD S. SPIELMAN2 & VIVIAN G. CHEUNG1,2,3
1 Department of Pediatrics and
2 Department of Genetics, University of Pennsylvania,
3 The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
* These authors contributed equally to this work
Correspondence and requests for materials should be addressed to V.G.C. (vcheung@mail.med.upenn.edu) or R.S.S. (spielman@pobox.upenn.edu).
The GEO accession number for the microarray data is GSE1485.
Natural variation in gene expression is extensive in humans and other organisms, and variation in the baseline expression level of many genes has a heritable component. To localize the genetic determinants of these quantitative traits (expression phenotypes) in humans, we used microarrays to measure gene expression levels and performed genome-wide linkage analysis for expression levels of 3,554 genes in 14 large families. For approximately 1,000 expression phenotypes, there was significant evidence of linkage to specific chromosomal regions. Both cis- and trans-acting loci regulate variation in the expression levels of genes, although most act in trans. Many gene expression phenotypes are influenced by several genetic determinants. Furthermore, we found hotspots of transcriptional regulation where significant evidence of linkage for several expression phenotypes (up to 31) coincides, and expression levels of many genes that share the same regulatory region are significantly correlated. The combination of microarray techniques for phenotyping and linkage analysis for quantitative traits allows the genetic mapping of determinants that contribute to variation in human gene expression.