(TG/CA)_nRepeats in Human Housekeeping Genes

Abstract

The unravelling of human genome sequence gives a new opportunity to investigate the role of repetitive sequences in gene regulation. Among the various types of repetitive sequences, the dinucleotide (TG:CA)(n) repeats are one of the most abundant in human genome and exhibit polymorphism. Early on, it was observed that the (TG:CA)(n) repeats could modulate gene expression and has the propensity to undergo conformational transitions in in vivo conditions. Recent reports describe the role of polymorphic (TG:CA)(n) repeats in gene regulation in several genes. In this work, we have analysed the distribution of (TG:CA)(n) (n >or= 6) repeats in human 'housekeeping genes' on which recently released Gene Chip data is available. Our results indicate that (i). The number of short intragenic (TG:CA)(n) repeats is significantly higher than the number of long repeats (ii). the proportion of genes with (TG:CA)(n) repeats (n >or= 12 units) had lower mean expression levels compared to those without these repeats, (iii). the genes belonging to the functional class of 'signalling and communication' had a positive association with repeats in contrast to the genes belonging to the 'information' class that were negatively associated with repeats.

Abundance of dinucleotide repeats and gene expression are inversely correlated: a role for gene function in addition to intron length

“…Uninterrupted (TG/CA) nՆ12 repeats (type II and type III) were identified as described previously (39,41). Repeats of these types have been shown to modulate transcription (2, 10, 16, 31, 32, 35, 39 -43).…”

“…These six broad functional classes were defined based on the scheme suggested by Adams et al (1) and Andrade et al (4) (also see Refs. [37][38][39]41). Two KOG categories (R, S) for "general function prediction only" and "unknown" functions were not included in the functional analysis.…”

CA Repeats in the 3′-Untranslated Region of bcl-2 mRNA Mediate Constitutive Decay of bcl-2 mRNA

“…Recently, a number of reports have described a correlation between the reduced expression levels of several genes such as IFN-␥ and HSD11B2 and either the presence of repeats or an increase in the length of the repeats in the intron, suggesting a regulatory function of CA repeats on the processing of pre-mRNAs (25)(26)(27). Furthermore, CA repeats in intron 13 of the human endothelial nitric-oxide synthase (eNOS) gene seem to specify the cleavage site of the pre-mRNA of eNOS for splicing or degradation, depending on the presence of heterogeneous nuclear ribonucleoprotein L (hnRNPL) (28,29).…”

Characterization of simple sequence repeat variants linked to candidate genes for behavioral phenotypes

“…Simple sequence repeat (SSR) loci, consisting of repeat units 2-5 base pairs in length, and minisatellites with longer repeat lengths (up to 65 base pairs) provide a possible mechanism for behavioral variation, as repeat length at many of these loci correlates with transcriptional efficiency and hence regulation of linked genes (Sabol, et al, 1998;Sharma, et al, 2003). Repeat length can also correspond to differential responsivity to environmental cues (Streelman and Kocher, 2002;Hammock and Young, 2005).…”