Intergenic and genic sequence lengths have opposite relationships with respect to gene expression.

Eukaryotic genomes are mostly composed of noncoding DNA whose role is still poorly understood. Studies in several organisms have shown correlations between the length of the intergenic and genic sequences of a gene and the expression of its corresponding mRNA transcript. Some studies have found a positive relationship between intergenic sequence length and expression diversity between tissues, and concluded that genes under greater regulatory control require more regulatory information in their intergenic sequences. Other reports found a negative relationship between expression level and gene length and the interpretation was that there is selection pressure for highly expressed genes to remain small. However, a correlation between gene sequence length and expression diversity, opposite to that observed for intergenic sequences, has also been reported, and to date there is no testable explanation for this observation. To shed light on these varied and sometimes conflicting results, we performed a thorough study of the relationships between sequence length and gene expression using cell-type (tissue) specific microarray data in Arabidopsis thaliana. We measured median gene expression across tissues (expression level), expression variability between tissues (expression pattern uniformity), and expression variability between replicates (expression noise). We found that intergenic (upstream and downstream) and genic (coding and noncoding) sequences have generally opposite relationships with respect to expression, whether it is tissue variability, median, or expression noise. To explain these results we propose a model, in which the lengths of the intergenic and genic sequences have opposite effects on the ability of the transcribed region of the gene to be epigenetically regulated for differential expression. These findings could shed light on the role and influence of noncoding sequences on gene expression.

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites.

PURPOSE: Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. METHODS: Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression. RESULTS: The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05). CONCLUSIONS: These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.