ABSTRACT
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.
Subject(s)
DNA Copy Number Variations , Exome Sequencing , Genetic Testing , Humans , Exome Sequencing/methods , India/epidemiology , Male , Genetic Testing/methods , Genetic Testing/economics , Female , High-Throughput Nucleotide Sequencing/methods , Exome/genetics , Consanguinity , Child , Adult , Adolescent , Child, Preschool , Phenotype , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/epidemiology , Infant , Young AdultABSTRACT
BACKGROUND/AIM: Gastric cancer (GC) is the fourth most common cancer and the second most common cause of cancer death world-wide after lung cancer. It is a multifactorial disease with the involvement of both genetic and environmental risk factors. Genetic variation in genes encoding cytokines and their receptors, determine the intensity of the inflammatory response, which may contribute to individual differences in severity of outcome of the disease. Tumor necrosis factor alpha (TNF-α) is a potent pro-inflammatory cytokine and acid inhibitor. A bi allelic G to A polymorphism at -308 upstream from the transcription initiation site of the promoter is associated with elevated TNF levels. The present study is aimed at evaluating the role of TNF-α-308 (G â A) gene polymorphism and susceptibility to GC. SUBJECTS AND METHODS: A case-control study was carried out in 114 GC patients and 229 healthy control subjects. TNF-α genotyping at position-308 (G â A) was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method followed by agarose gel electrophoresis. RESULTS: The distribution of TNF-α genotypes at -308 (G â A) were GG 28.07%, GA 66.67% and AA 5.26% in GC patients and GG 33.19%, GA 55.89% and AA 10.92% in control subjects. The frequencies of alleles G and A were 0.614 and 0.386 in GC patients and 0.611 and 0.389 in control subjects respectively. CONCLUSION: The study showed no significant difference in the distribution of genotype and allelic frequencies between GC patients and control subject.
