RESUMO
The genetically isolated yet heterogeneous and highly consanguineous Indian population has shown a higher prevalence of rare genetic disorders. However, there is a significant socioeconomic burden for genetic testing to be accessible to the general population. In the current study, we analyzed next-generation sequencing data generated through focused exome sequencing from individuals with different phenotypic manifestations referred for genetic testing to achieve a molecular diagnosis. Pathogenic or likely pathogenic variants are reported in 280 of 833 cases with a diagnostic yield of 33.6%. Homozygous sequence and copy number variants were found as positive diagnostic findings in 131 cases (15.7%) because of the high consanguinity in the Indian population. No relevant findings related to reported phenotype were identified in 6.2% of the cases. Patients referred for testing due to metabolic disorder and neuromuscular disorder had higher diagnostic yields. Carrier testing of asymptomatic individuals with a family history of the disease, through focused exome sequencing, achieved positive diagnosis in 54 of 118 cases tested. Copy number variants were also found in trans with single-nucleotide variants and mitochondrial variants in a few of the cases. The diagnostic yield and the findings from this study signify that a focused exome test is a good lower-cost alternative for whole-exome and whole-genome sequencing and as a first-tier approach to genetic testing.
Assuntos
Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Testes Genéticos , Humanos , Sequenciamento do Exoma/métodos , Índia/epidemiologia , Masculino , Testes Genéticos/métodos , Testes Genéticos/economia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Exoma/genética , Consanguinidade , Criança , Adulto , Adolescente , Pré-Escolar , Fenótipo , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/epidemiologia , Lactente , Adulto JovemRESUMO
OBJECTIVE: CRP gene polymorphism is common in inflammatory diseases, but such association has not been reported in periodontitis. Our objective was to interrogate SNPs of crp in chronic periodontitis in a case-control manner. METHODS: DNAs were extracted from mouthwash samples of 116 volunteers using salting-out method. Selected 12 5'UTR SNPs of crp were genotyped using ARMS-PCR. RESULTS: TC genotype of - 757T > C polymorphism (rs3093059) showed protective association (OR- 0.29, 95%CI-0.12-0.68, and p-0.004), and wild type - 757TT showed susceptible association with a p value of 0.008 (OR-3.09, 95%CI-1.33-7.15). CONCLUSION: The observation of protective and susceptible association of crp - 757T > C polymorphism may be useful for better management and prophylaxis of periodontitis.