Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Exploring New Biomarkers for Autoimmune Thyroid Diseases Through Whole Exome Sequencing and Pathway-Based Enrichment
Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, represent common multifactorial conditions arising from a complex interplay of genetic and environmental factors. Despite extensive research employing family and population-based approaches, alongside varied genome screening resolutions, the complete understanding of AITD pathophysiology remains elusive, largely due to the genetic and allelic heterogeneity of the disease. In this work, next-generation sequencing (NGS) is employed to explore the whole exome of seven patients from a large multiplex family. The whole exome sequencing (WES) data is subjected to meticulous filtration. Variants of genes localized on the IDDM6 locus (18q21) are analyzed as positional candidates. By means of computational functional assessments and in silico variant prediction tools, the p.Phe532Ser variant of the polymerase iota (POLI) gene, member of the DNA repair machinery genes, is selected as the most pathogenic variant. The remaining DNA repair genes variants are evaluated and another pathogenic variant in 8-oxoguanine-DNA glycosylase (OGG1) gene (p.Arg229Gln) is selected. Both selected functional variants are genotyped by direct sequencing among the family members. The statistical analysis demonstrates a high prevalence of the minor alleles of both variants among the patients compared to healthy members. The findings of this study underscore the exceptional value and significance of both POLI and OGG1 as promising candidates for AITD pathogenesis.
Exploring New Biomarkers for Autoimmune Thyroid Diseases Through Whole Exome Sequencing and Pathway-Based Enrichment
Autoimmune thyroid diseases (AITD), including Graves' disease and Hashimoto's thyroiditis, represent common multifactorial conditions arising from a complex interplay of genetic and environmental factors. Despite extensive research employing family and population-based approaches, alongside varied genome screening resolutions, the complete understanding of AITD pathophysiology remains elusive, largely due to the genetic and allelic heterogeneity of the disease. In this work, next-generation sequencing (NGS) is employed to explore the whole exome of seven patients from a large multiplex family. The whole exome sequencing (WES) data is subjected to meticulous filtration. Variants of genes localized on the IDDM6 locus (18q21) are analyzed as positional candidates. By means of computational functional assessments and in silico variant prediction tools, the p.Phe532Ser variant of the polymerase iota (POLI) gene, member of the DNA repair machinery genes, is selected as the most pathogenic variant. The remaining DNA repair genes variants are evaluated and another pathogenic variant in 8-oxoguanine-DNA glycosylase (OGG1) gene (p.Arg229Gln) is selected. Both selected functional variants are genotyped by direct sequencing among the family members. The statistical analysis demonstrates a high prevalence of the minor alleles of both variants among the patients compared to healthy members. The findings of this study underscore the exceptional value and significance of both POLI and OGG1 as promising candidates for AITD pathogenesis.
Exploring New Biomarkers for Autoimmune Thyroid Diseases Through Whole Exome Sequencing and Pathway-Based Enrichment
Younsou, Roa M. (Autor:in) / Moalla, Mariam (Autor:in) / Kallel, Rihab (Autor:in) / Kifagi, Chamseddine (Autor:in) / Bougacha-Elleuch, Noura (Autor:in) / Ghorbel, Achraf (Autor:in) / Ayadi, Hammadi (Autor:in) / Abid, Mohamed (Autor:in) / Mnif-Feki, Mouna (Autor:in) / Kacem, Hassen Hadj (Autor:in)
03.06.2024
887701 byte
Aufsatz (Konferenz)
Elektronische Ressource
Englisch
| British Library Online Contents | 2013
Bullous Autoimmune Diseases in Humans
| British Library Conference Proceedings | 1997
Immunomodulatory Vaccines Against Autoimmune Diseases
| British Library Online Contents | 2006