Large scale genomic analysis of 3067 SARS-1 CoV-2 genomes reveals a clonal geo-distribution 2 and a rich genetic variations of hotspots 3 mutations 4 Abstract 33In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, 34China, and became a global pandemic. Characterization of the genetic variants of SARS-35CoV-2 is crucial in following and evaluating it spread across countries. In this study, we 36 collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the 37 first three months after the onset of this virus. Using comparative genomics analysis, we 38 traced the profiles of the whole-genome mutations and compared the frequency of each 39 mutation in the studied population. The accumulation of mutations during the epidemic 40 period with their geographic locations was also monitored. The results showed 782 variant 41 sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles 42 revealed the presence of 38 recurrent non-synonymous mutations, including ten hotspot 43 mutations with a prevalence higher than 0.10 in this population and distributed in six 44 SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map 45 revealed certain genotypes specific to the geographic location. We also found co-occurring 46 mutations resulting in the presence of several haplotypes. Moreover, evolution over time 47We have also created an inclusive unified database (http://genoma.ma/covid-19/) that lists 52 all of the genetic variants of the SARS-CoV-2 genomes found in this study with 53 phylogeographic analysis around the world. 54 55 56
In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variants sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 68 recurrent mutations, including ten hotspot non-synonymous mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed that certain genotypes are specific to geographic locations. We also identified co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. The phylogentic analysis identified two major Clades C1 and C2 harboring mutations L3606F and G614D, respectively and both emerging for the first time in China. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets. We have also created an inclusive unified database (http://covid-19.medbiotech.ma) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.
The coronavirus pandemic, which appeared in Wuhan, China, in December 2019, rapidly spread all over the world in only a few weeks. Faster testing techniques requiring less resources are key in managing the pandemic, either to enable larger scale testing or even just provide developing countries with limited resources, particularly in Africa, means to perform tests to manage the crisis. Here, we report an unprecedented, rapid, reagent-free and easy-to-use screening spectroscopic method for the detection of SARS-CoV-2 on RNA extracts. This method, validated on clinical samples collected from 280 patients with quantitative predictive scores on both positive and negative samples, is based on a multivariate analysis of FTIR spectra of RNA extracts. This technique, in agreement with RT-PCR, achieves 97.8% accuracy, 97% sensitivity and 98.3% specificity while reducing the testing time post RNA extraction from hours to minutes. Furthermore, this technique can be used in several laboratories with limited resources.
Abstract. At present, breast cancer is the most common type of cancer in females. The majority of cases are sporadic, but 5-10% are due to an inherited predisposition to develop breast and ovarian cancers, which are transmitted as an autosomal dominant form with incomplete penetrance. The beneficial effects of clinical genetic testing, including next generation sequencing (NGS) for BRCA1/2 mutations, is major; in particular, it benefits the care of patients and the counseling of relatives that are at risk of breast cancer, in order to reduce breast cancer mortality. BRCA genetic testing was performed in 15 patients with breast cancer and a family with positivity for the heterozygous c.6428C>A mutation of the BRCA2 gene. Informed consent was obtained from all the subjects. Genomic DNAs were extracted and the NGS for genes was performed using the Ion Torrent Personal Genome Machine (PGM) with a 316 chip. The reads were aligned with the human reference HG19 genome to elucidate variants in the BRCA1 and BRCA2 genes. Mutations detected by the PGM platform were confirmed by target direct Sanger sequencing on a second patient DNA sample. In total, 4 BRCA variants were identified in 6 families by NGS. Of these, 3 mutations had been previously reported: c.2126insA of BRCA1, and c.1310_1313delAAGA and c.7235insG of BRCA2. The fourth variant, c.3453delT in BRCA1, has, to the best of our knowledge, never been previously reported. The present study is the first to apply NGS of the BRCA1 and BRCA2 genes to a Moroccan population, prompting additional investigation into local founder mutations and variant characteristics in the region. The variants with no clear clinical significance may present a diagnostic challenge when performing targeted resequencing. These results confirm that an NGS approach based on Ampliseq libraries and PGM sequencing is a highly efficient, speedy and high-throughput mutation detection method, which may be preferable in lower income countries. IntroductionAt present, breast cancer is the most common type of cancer in females (1). The majority of cases are sporadic, but 5-10% are due to an inherited predisposition to develop breast and ovarian cancers, which are transmitted as an autosomal dominant form with incomplete penetrance (2,3). Germline mutations of BRCA1 and BRCA2 genes are involved in ~10 and 3-5% of ovarian and breast cancers, respectively (4,5). According to various professional society guidelines, BRCA1 and BRCA2 hereditary breast and ovarian cancer is characterised by: Multiple family members that possess breast, ovarian or both cancers; occurring at young ages or bilaterally in the case of breast cancer, triple-negative (estrogen receptor-, progesterone receptor-and human epidermal growth factor receptor 2/neu-negative) breast cancer and male breast cancer; and an increased risk of prostate, pancreatic and endometrial cancers (6,7). BRCA1 and BRCA2 are tumor suppressor genes associated with DNA damage recognition, double-strand break repair, checkpoint control, transcription regulation ...
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