Several human genes are known which are induced by copper in various human cell lines.
The use of traditional model organisms that are relatively closely related to humans (including primates, mice, and, more recently, zebrafish) has been quite successful in yielding results that can translate to humans [ 10- 15], but more distantly related animals have also been utilized for studying various human disease genes and diseases.
It is well known that malignant transformation of human cancer cells is a multi-staged process involving mutation or deletions of various human suppressor's genes.
Yu et al. [ 9] addressed this issue by identifying motif pairs with biased distance distributions in various sets of human genes that exhibited tissue-specific expression, and Long et al. [ 10] identified motif pairs over-represented in promoters of immune-response genes.
In human genes, various domains have been shown to be more often spliced-out than average [ 19].
Since promoter hypermethylation is responsible for transcriptional silencing of important tumour suppressor genes in various human cancer types [ 30], we searched all three EDN genes for the presence of CpG islands in their promoter region.
Analysis of approximately 1 Mb of contiguous DNA surrounding the functional class II region in zebrafish demonstrates the presence of 23 flanking genes mapping to various human chromosomal locations, including two or more genes mapping to human 6q (C6orf117, LOC557721, ppil4), 12q (slc15a4, KIAA1944), 20q (rnpc2, slc12a5), 22q (sf3a14, sf3and and Xp (pqbp1l, t541, jarid1c).
For example, Hsu et al. [ 26] integrated a GWAS of Caucasians with gene expression profiling of various human tissues and identified three novel genes associated with BMD - RAP1A (encoding a Ras oncogene family member), TBC1D8 (TBC1 domain family member 8), and OSBPL1A (oxysterol binding protein-like 1A) - and replicated the identification of OPG (osteoprotegerin) [ 26].
To categorize the SAE-expressed genes in healthy nonsmokers as ubiquitous (i.e., expressed by most other tissues) or genes expressed in an SAE-enriched fashion, a comparison was made between the 7,897 genes identified by Ramsköld et al [ 24] to be ubiquitously expressed in various human tissues and the 15,877 genes expressed in human SAE.
