Genetic variation of the intelectin gene family implicated in inflammatory disease and mesothelioma

The human intelectin protein 1 (hItln1), coded by the ITLN1 gene, is expressed in the intestine. It recognizes and binds with multiple glycans that found solely on bacteria. A genome wide association study (GWAS) identified SNP, rs2274910, found in the ITLN1 gene that contributes to the risk of having Crohn’s disease (CD). However, the variant functionally responsible for this association with CD has not yet been identified.

Several copy number variants (CNV) overlapping ITLN1 have already been identified. However, a putative duplication and a deletion were not validated, suggesting these were false positive calls. Another deletion was confirmed to be an in-frame deletion found in the African population. However, it is rare, and it does not explain the GWAS signal found in Europeans.

The C57BL/6, the reference mouse genome, has a single Itln gene, yet the 129S7 strain has 6 Itln genes. Thus, any variation within the Itln locus were not able to be identified (except Itln1). To investigate the variation of these Itln genes, we realigned Illumina short read sequence reads from several inbred mouse strains and wild-caught mice to the BAC contig spanning the highly repetitive Itln locus generated from a single 129S7 strain mouse. Using sequence read depth, a deletion in the C57BL/6 strains was confirmed and several distinct deletions were identified. Analysis of sequence variation also suggested polymorphic variants introducing early stop codons in particular Itln genes.

Several studies demonstrated the ITLN1 gene shows the highest expression level in mesothelioma tissue samples, compared to normal tissues and it could therefore be a potential tumour biomarker for mesothelioma. To validate this, an expression analysis of ITLN1 was carried out on several mesothelioma tissues and correlated with clinical parameters in a small patient cohort. A significant relationship between the expression level of ITLN1 and the survival time after surgery was revealed.