title: Genomic expression differences between cutaneous cells from red hair color individuals and black hair color individuals based on bioinformatic analysis.
abstract: The MC1R gene plays a crucial role in pigmentation synthesis. Loss-of-function MC1R variants, which impair protein function, are associated with red hair color (RHC) phenotype and increased skin cancer risk. Cultured cutaneous cells bearing loss-of-function MC1R variants show a distinct gene expression profile compared to wild-type MC1R cultured cutaneous cells. We analysed the gene signature associated with RHC co-cultured melanocytes and keratinocytes by Protein-Protein interaction (PPI) network analysis to identify genes related with non-functional MC1R variants. From two detected networks, we selected 23 nodes as hub genes based on topological parameters. Differential expression of hub genes was then evaluated in healthy skin biopsies from RHC and black hair color (BHC) individuals. We also compared gene expression in melanoma tumors from individuals with RHC versus BHC. Gene expression in normal skin from RHC cutaneous cells showed dysregulation in 8 out of 23 hub genes (CLN3, ATG10, WIPI2, SNX2, GABARAPL2, YWHA, PCNA and GBAS). Hub genes did not differ between melanoma tumors in RHC versus BHC individuals. The study suggests that healthy skin cells from RHC individuals present a constitutive genomic deregulation associated with the red hair phenotype and identify novel genes involved in melanocyte biology.
authors.affiliation: Biochemistry and Molecular Genetics Department, Melanoma Unit, Hospital Clinic & IDIBAPS, CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain.
authors.forename: Joan Anton
authors.initials: JA
authors.lastname: Puig-Butille
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS, CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain.
authors.forename: Pol
authors.initials: P
authors.lastname: Gimenez-Xavier
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Alessia
authors.initials: A
authors.lastname: Visconti
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Nsengimana
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-García
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS, CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Tell-Marti
authors.affiliation: Departamento de Bioingeniería, Universidad Carlos III de Madrid, CIEMAT, IIS-Fundación Jiménez Díaz, CIBER de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Escamez
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Newton-Bishop
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Veronique
authors.initials: V
authors.lastname: Bataille
authors.affiliation: Departamento de Bioingeniería, Universidad Carlos III de Madrid, CIEMAT, IIS-Fundación Jiménez Díaz, CIBER de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Marcela
authors.initials: M
authors.lastname: Del Río
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Functional Genomics Node, (INB) at CIPF, Valencia, Spain.|CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.affiliation: Dermatology Department, Melanoma Unit, Hospital Clinic & IDIBAPS, CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
mesh_terms: D000328:Adult; D018920:Coculture Techniques; D019295:Computational Biology / Q000379:methods; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006200:Hair Color / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D008544:Melanocytes / Q000502:physiology*; D008875:Middle Aged; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics
chemical_list: D044102:Receptor, Melanocortin, Type 1
keywords: MC1R; autophagy; melanocyte; melanoma; red hair phenotype