Abstract
We have mapped a locus on chromosome 7p22.3-7p15.3 spanning a 22.4 Mb region for ulcerative colitis (UC) by whole genome linkage analyses of a large Danish family. The family represent three generations with UC segregating as an autosomal dominant trait with variable expressivity. The whole-genome scan resulted in a logarithm of odds score (LOD score) of Z = 3.31, and a whole genome sequencing (WGS) of two affected excluded disease-causing mutations in the protein coding genes. Two rare heterozygote variants, rs182281985:G>A and rs541426369:G>A, both with low allele frequencies (MAF A:0.0001, gnomAD ver3.1.2), were found in clusters of ChiP-seq transcription factors binding sites close to the AHR (aryl hydrocarbon receptor) gene and the UC associated SNP rs1077773:G>A. Testing the two SNPs in a promoter reporter assay for regulatory activity revealed that rs182281985:G>A influenced the AHR promoter. These results suggest a regulatory region that include rs182281985:G>A close to the UC GWAS SNP rs1077773:G>A and further demonstrate evidence that the AHR gene on the 7p-tel region is a candidate susceptible gene for UC.
Original language | English |
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Journal | European journal of human genetics : EJHG |
Volume | 31 |
Issue number | 12 |
Pages (from-to) | 1440-1446 |
Number of pages | 7 |
ISSN | 1018-4813 |
DOIs | |
Publication status | Published - Dec 2023 |
Keywords
- Colitis, Ulcerative/genetics
- Genetic Linkage
- Humans
- Phenotype
- Polymorphism, Single Nucleotide
- Receptors, Aryl Hydrocarbon/genetics