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1.  Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells 
PLoS ONE  2015;10(7):e0132957.
For multiple sclerosis, genome wide association studies and follow up studies have identified susceptibility single nucleotide polymorphisms located in or near CLEC16A at chromosome 16p13.13, encompassing among others CIITA, DEXI and SOCS1 in addition to CLEC16A. These genetic variants are located in intronic or intergenic regions and display strong linkage disequilibrium with each other, complicating the understanding of their functional contribution and the identification of the direct causal variant(s). Previous studies have shown that multiple sclerosis-associated risk variants in CLEC16A act as expression quantitative trait loci for CLEC16A itself in human pancreatic β-cells, for DEXI and SOCS1 in thymic tissue samples, and for DEXI in monocytes and lymphoblastoid cell lines. Since T cells are major players in multiple sclerosis pathogenesis, we have performed expression analyses of the CIITA-DEXI-CLEC16A-SOCS1 gene cluster in CD4+ and CD8+ T cells isolated from multiple sclerosis patients and healthy controls. We observed a higher expression of SOCS1 and CLEC16A in CD4+ T cells in samples homozygous for the risk allele of CLEC16A rs12927355. Pair-wise linear regression analysis revealed high correlation in gene expression in peripheral T cells of CIITA, DEXI, CLEC16A and SOCS1. Our data imply a possible regulatory role for the multiple sclerosis-associated rs12927355 in CLEC16A.
PMCID: PMC4512731  PMID: 26203907
2.  Dact1-3 mRNAs exhibit distinct expression domains during tooth development 
Gene expression patterns : GEP  2010;10(2-3):140-143.
Wnt signaling is essential for tooth formation. Dact proteins modulate Wnt signaling by binding to the intracellular protein Dishevelled (Dvl). Comparison of all known mouse Dact genes, Dact1-3, from the morphological initiation of mandibular first molar development after the onset of the root formation using sectional in situ hybridization showed distinct, complementary and overlapping expression patterns for the studied genes. While Dact2 expression was restricted to the dental epithelium including the enamel knot signaling centers and tooth specific preameloblasts, Dact1 and Dact3 showed developmentally regulated expression in the dental mesenchyme. Both mRNAs were first detected in the presumptive dental mesenchyme. After being downregulated from the condensed dental mesenchyme of the bud stage tooth germ, Dact1 was upregulated in the dental follicle masenchyme at the cap stage and subsequently also in the dental papilla at the bell stage where the expression persisted to the postnatal stages. In contrast, Dact3 transcripts persisted throughout the dental mesenchymal tissue components including the tooth-specific cells, preodontoblasts before transcripts were largely downregulated from the tooth germ postnatally. Collectively these results suggest that Dact1 and -3 may contribute to early tooth formation by modulation of Wnt signaling pathways in the mesenchyme, including preodontoblasts, whereas Dact2 may play important signal-modulating roles in the adjacent epithelial cells including the enamel knot signaling centers and preameloblasts. Future loss-of-function studies will help elucidate whether any of these functions are redundant, particularly for Dact1 and Dact3.
PMCID: PMC2849867  PMID: 20170752

Results 1-2 (2)