biostudies-literatureMontandon SAFonds Général de l'Université de GenèveSara Borrell grantHuman Frontier Science ProgramSwiss National Science FoundationEmile Plantamour FundErnst and Lucie Schmidheiny Foundation73https://www.ebi.ac.uk/biostudies/studies/S-EPMC11948899biostudies-literatureUnknown26(1)<h4>Background</h4>Snakes exhibit a broad variety of adaptive colors and color patterns, generated by the spatial arrangement of chromatophores, but little is known of the mechanisms responsible for these spectacular traits. Here, we investigate a mono-locus trait with two recessive alleles, motley and stripe, that both cause pattern aberrations in the corn snake.<h4>Results</h4>We use mapping-by-sequencing to identify the genomic interval where the causal mutations reside. With our differential gene expression analyses, we find that CLCN2 (Chloride Voltage-Gated Channel 2), a gene within the genomic interval, is significantly downregulated in Motley embryonic skin. Furthermore, we identify the stripe allele as the insertion of an LTR-retrotransposon in CLCN2, resulting in a disruptive mutGenome biologyRegulatory and disruptive variants in the CLCN2 gene are associated with modified skin color pattern phenotypes in the corn snake.PMC11948899CD22/0002720446610_2023RGP0037/2022140785310030_2044662024/1231003A_14078531003023_28Ullate-Agote AAndersson LTzika ACMilinkovitch MCKummrow MRoig-Puiggros SMontandon SABeaudier PJabaudon DHelleboid PYfalseRegulatory and disruptive variants in the CLCN2 gene are associated with modified skin color pattern phenotypes in the corn snake.<h4>Background</h4>Snakes exhibit a broad variety of adaptive colors and color patterns, generated by the spatial arrangement of chromatophores, but little is known of the mechanisms responsible for these spectacular traits. Here, we investigate a mono-locus trait with two recessive alleles, motley and stripe, that both cause pattern aberrations in the corn snake.<h4>Results</h4>We use mapping-by-sequencing to identify the genomic interval where the causal mutations reside. With our differential gene expression analyses, we find that CLCN2 (Chloride Voltage-Gated Channel 2), a gene within the genomic interval, is significantly downregulated in Motley embryonic skin. Furthermore, we identify the stripe allele as the insertion of an LTR-retrotransposon in CLCN2, resulting in a disruptive mut2025-01-01T00:00:00Z2025 Mar2026-06-01T22:59:40.875Z2025-07-13T03:04:49.044ZS-EPMC119488994014090010.1186/s13059-025-03539-0