RESUMO
Atopic dermatitis (AD) is a chronic, inflammatory skin condition with a multifactorial pathophysiology. The filaggrin gene (FLG) has particularly been implicated given loss of function (LoF) mutations in this gene lead to skin barrier dysfunction and such mutations can increase a patient's likelihood of developing AD. FLG has intragenic copy number variation (CNV), which impacts the total amount of filaggrin produced. Previous research reported a dose-dependent effect such that as amount of FLG increases, risk of AD decreases. To gain a better understanding, we evaluated FLG CNV in a large case-control study of Whites and Blacks with and without AD. The goal of our study was to determine whether FLG CNV has a dose-dependent effect on the risk of developing AD and to determine whether FLG CNV varies by race. The frequencies and odds ratios comparing a given CNV by race or race within those with AD did not significantly vary. It had been thought that FLG CNV might vary by race and represent an important association with AD in Black AD subjects. However, our work suggests that while there are racial differences with respect to CNV, these differences do not appear to explain AD risk.
Assuntos
Dermatite Atópica , Proteínas Filagrinas , Negro ou Afro-Americano/genética , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Dermatite Atópica/genética , Humanos , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismo , MutaçãoAssuntos
Negro ou Afro-Americano/genética , Variações do Número de Cópias de DNA , Dermatite Atópica/genética , Proteínas S100/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Dermatite Atópica/epidemiologia , Feminino , Proteínas Filagrinas , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto JovemRESUMO
We have generated an induced pluripotent stem cell (iPSC) line KCLi003-A (iOP101) from epidermal keratinocytes of a female donor, heterozygous for the loss-of-function mutation p.R501X in the filaggrin gene (FLG), using non-integrating Sendai virus vectors. Derivation and expansion of iPSCs were performed under xeno-free culture conditions. Characterization and validation of KCLi003-A line included molecular karyotyping, mutation screening using restriction enzyme digestion, next generation sequencing (NGS), while pluripotency and differentiation potential were confirmed by expression of associated markers in vitro and by in vivo teratoma assay.
Assuntos
Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas de Filamentos Intermediários/genética , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Proteínas Filagrinas , Imunofluorescência , Heterozigoto , Humanos , Repetições de Microssatélites/genética , Mycoplasma/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vírus Sendai/genéticaRESUMO
We have generated an induced pluripotent stem cell (iPSC) line KCLi002-A (iOP107) from a female donor, heterozygous for the loss-of-function mutation p.R2447X in the filaggrin gene (FLG). Epidermal keratinocytes were reprogrammed using non-integrating Sendai virus vectors. The entire process of derivation and expansion of iPSCs were performed under xeno-free culture conditions. Characterization of KCLi002-A line included molecular karyotyping, mutation screening using restriction enzyme digestion Sanger sequencing and next generation sequencing (NGS), whereas pluripotency and differentiation potential were confirmed by expression of associated markers in vitro and in vivo teratoma assay.