A family with ulcerative colitis maps to 7p21.1 and comprises a region with regulatory activity for the aryl hydrocarbon receptor gene

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Fulltext

    Accepteret manuskript, 398 KB, PDF-dokument

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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Human Genetics
Vol/bind31
Sider (fra-til)1440-1446
Antal sider7
ISSN1018-4813
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We thank all family members for their participation in this study and Annemette Friis Mikkelsen and Marianne Lauridsen is thanked for excellent technical assistance and Rigshospitalets Microarray Center for the genotyping. HE was supported by the Danish Medical Research Council (22-02-0208), CBB by the Innovation Fund Denmark (0603-00320B), JTT and JBO received funding from Region Zealand and Roskilde University.

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to European Society of Human Genetics.

ID: 337596491