Clinical exome sequencing is currently being used in diagnostics of various genetic disorders, but studies supporting its application in clinical setting are scarce. The aim of this study was to establish diagnostic and clinical utility of clinical exome sequencing in patients with moderate and severe global developmental delay/intellectual disability. Clinical diagnosis was made in 49 of 88 investigated patients, with overall diagnostic yield of 55.7%. Molecular findings are characterized in detail, including the impact of newly made diagnosis on clinical management. Several previously unreported genotype-phenotype correlations and 33 novel variants are described. Genetic and clinical data were shared through publicly available database. In conclusion, clinical exome sequencing allows identification of causative variants in a significant proportion of patients in investigated clinical subgroup. Compared to whole exome sequencing, it shows similar diagnostic and clinical utility with reduced costs, which could be of particular importance for institutions with limited resources.
AbstractConsidering the importance of the TGF-β signaling pathway for normal lung function and especially its roles in inflammation and tissue remodeling, key features of asthma pathology, it can be assumed that these molecules may harbor mutations in asthmatics. The aim of this study was to analyze the SMAD4 gene in patients with asthma. Analysis has encompassed exons 10, 11, 12 and 13 encoding the carboxy-terminal (MH2) domain of the SMAD4 protein, where mutations most frequently occur. The study included 50 patients (20 men and 30 women) with asthma aged between 17 and 73 years (average age 45.2±15.6 years). Polymerase chain reaction (PCR) was used to amplify exons 10, 11, 12 and 13 of the SMAD4 gene and the obtained PCR products were subjected to direct DNA sequencing. No nucleotide changes were found in any of the analyzed exons in either of the subjects. Based on the results of this study, it seems that mutations in the carboxy-terminal (MH2) domain of the SMAD4 are not present in asthmatic patients. Future research should be directed at the analysis of the complete gene, including regulatory elements, in order to resolve the exact role of SMAD4 in asthma.
Domestikacija, selekcija i moderno oplemenjivanje suzili su genetičku varijabilnost ječma, a time stvorili potrebu za ponovnim stvaranjem varijabilnosti kao baze za oplemenjivanje ove biljne vrste. U radu je tokom dve godine ispitivano 4 sorte ječma i 48 lokalnih populacija iz Banke biljnih gena Srbije. Analizirana je fenotipska varijabilnost i genetička struktura dve kvantitativne osobine klasa: dužina i širina klasa, i jedna osobina zrna: masa 1000 zrna, u populaciji sa genotipovima poznatog tipa vegetacije i oblika klasa. Prosečna dužina klasa iznosila je 4,2-10,2 cm, širina 0,65-1,27 cm, a masa 1000 zrna 27,58-51,35 g. Analiza varijanse imala je značajnu F vrednost za sve izvore variranja kod svih osobina. Analizom šesnaest SSR markera detektovano je ukupno 105 alelnih formi. Posmatrajući grupe, tip vegetacije i oblik klasa, diverzitet gena je bio najveći kod jarog (dvoredog i šestoredog) i šestoredog (jarog i ozimog) ječma. Rezultati AMOVA testa za oblik klasa su pokazali visoko značajne vrednosti za oba izvora varijacije, dok je međugrupna komponenta bila dominantna i za tip vegetacije (91,26%) i za oblik klasa (90,83%). UPGMA klaster analizom konstruisan je dendogram kojim su 52 genotipa svrstana u tri glavne grupe i 11 podgrupa. Dobijeni rezultati su pokazali da u proučavanoj kolekciji postoji značajna varijabilnost ispitivanih osobina, koja se može koristiti u oplemenjivačkim programima ječma.
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