Περίληψη:
Background: Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic. Methods: Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition. Results: Analysis revealed six genomic variants of prime interest: SLC9A4 c.1919G>A, KIAA1109 c.2933T>C and c.4268-4269delCCinsTA, HoxB6 c.668C>A, HoxD12 c.418G>A, and NCK2 c.745-746delAAinsG, from which NCK2 c.745-746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n = 109) and Serbian (n = 73) descent and their healthy counterparts (n = 111 and n = 32, respectively) indicated that HoxD12 c.418G>A is more prevalent in celiac disease patients in the Serbian population (P < 0.01), while NCK2 c.745-746delAAinsG is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P = 0.03). SLC9A4 c.1919G>A and KIAA1109 c.2933T>C and c.4268-4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance. Conclusions: The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology. © 2016 The Author(s).
Συγγραφείς:
Balasopoulou, A.
Stanković, B.
Panagiotara, A.
Nikčevic, G.
Peters, B.A.
John, A.
Mendrinou, E.
Stratopoulos, A.
Legaki, A.I.
Stathakopoulou, V.
Tsolia, A.
Govaris, N.
Govari, S.
Zagoriti, Z.
Poulas, K.
Kanariou, M.
Constantinidou, N.
Krini, M.
Spanou, K.
Radlovic, N.
Ali, B.R.
Borg, J.
Drmanac, R.
Chrousos, G.
Pavlovic, S.
Roma, E.
Zukic, B.
Patrinos, G.P.
Katsila, T.
Λέξεις-κλειδιά:
genomic DNA; immunoglobulin A; integrin; interleukin 2; interleukin 21; microRNA; protein glutamine gamma glutamyltransferase 2, Article; bioinformatics; celiac disease; cell adhesion; cell motility; clinical article; controlled study; DNA isolation; endothelium cell; gene; gene frequency; gene replication; genetic analysis; genetic predisposition; genetic risk; genetic susceptibility; genetic variability; genomics; Greece; HoxB6 gene; HoxD12 gene; human; KIAA1109 gene; NCK2 gene; next generation sequencing; protein structure; Serbian (citizen); single nucleotide polymorphism; SLC9A4 gene; binding site; celiac disease; child; genetic association study; genetics; high throughput sequencing; molecular model; mutation; risk factor, Binding Sites; Celiac Disease; Child; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Models, Molecular; Mutation; Polymorphism, Single Nucleotide; Risk Factors
