Expression Studies

Gene expression, a determinant of a cell's characteristics, is another phenotype that can be studied using lymphoblastoid cell lines. Studies have shown that gene expression levels in humans differ not only among cell types within an individual, but also among individuals (16,31). As a result, there have been several recent studies that have identified polymorphic genetic variants that influence gene expression levels (15,25,32).

Expression data on 233 CEPH cell lines using the Human Genome Focus1® Array representing over 8,500 verified human sequences from the NCBI RefSeq database is publicly available (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1485) and can be used for correlation and regression analysis with cytotoxicity and apoptosis. One use of this data to obtain information on gene expression that is important in drug sensitivity/resistance is to use vitro phenotype (e.g., cytotoxicity, apoptosis) as a continuous variable and use correlation and/or regression analyses to determine the effect of gene expression on phenotype for each probe set (4,276 probe sets after filtering). One limitation is that the Focus array does not represent the entire genome

(www.affymetrix.com/products/arrays/specific/focus.affx) and there is a 3 bias in probe design. There has also been data generated on 90 CEPH and 90 Yoruban cell lines at the baseline using the Human Exon 1.0 ST GeneChip® array. Containing roughly 1.4 million probe sets designed to represent all known exon regions within the human genome (Build 34), this exon chip overcomes the two limitations of the earlier Focus1® Array (8,500 probesets and the 3 bias in probe design). This array allows exon-level profiling and the ability to interrogate each exon across the genome on a single chip. Gene expression data for the 180HapMap lines can be correlated to phenotypes (IC50 for cytotoxicity and apoptosis).

Differences among individuals has led to several studies demonstrating expression differences among populations. Recently, ethnic differences in gene expression as a complex quantitative phenotype and its regulation by polymorphic genetic variants have not been investigated comprehensively. Spielman et al. utilized a subset of human genes (~4,200 expressed in LCLs) with samples derived from unrelated individuals from the CEU (CEPH from Utah, USA) and the CHB/JPT (Han Chinese in Beijing and Japanese in Tokyo) samples to demonstrate that cis-acting regulators may account for some of the differences in gene expression between the populations (33). Using the same platform, Storey et al. showed that 17% of genes are differentially expressed between CEU and YRI (Yoruban from Ibadan, Nigeria) in a limited set of 16 samples (34).

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment