一種大規(guī)模繪制基因圖譜的新穎方法,，被用來顯示一組其表達在人類B細胞中似乎是受遺傳控制的基因,，同時用來繪制控制這些基因表達的因子的圖譜。通過將微陣列方法和定量特性分析方法結(jié)合起來,，研究人員找到了控制1000個以上基因的表達的染色體位點以及引起其自然變異的復(fù)雜的轉(zhuǎn)錄調(diào)節(jié)網(wǎng)絡(luò),。該方法有可能用在對疾病來說重要的組織中，幫助識別復(fù)雜疾病的遺傳病因,。
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. ([email protected]) or R.S.S. ([email protected]).
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.
