Analysis of BRCA1 germline variants (exons 5, 11 and 20) in breast cancer families from Libya.

Breast cancer (BC) is a leading cause of cancer deaths in Libyan women. BRCA1 variants differ globally due to the diversity of genetic makeup and populations history. Their distribution, prevalence, and significance in Libyans remain largely unexplored. This study investigated the characteristics and distribution of BRCA1 variants in exons 5, 11, and 20 in Libyan families with BC. Thirty-six BC patients at ≤ 45 years, between 46-50 years and with a family history of breast, ovarian, pancreatic or prostate cancer in close relatives, or with triple-negative BC, were selected from 33 unrelated families during 2018-2020 at the National Cancer Institute, Sabratha, Libya. From these 33 families, 20 women (18 BC patients and two unaffected) were screened for BRCA1 exons 5, 11 and 20 using Sanger sequencing. All families completed an epidemiology and family history questionnaire. Twenty-seven variants (26 in exon 11 and 1 in exon 20, minor allele frequency of < 0.01) were detected in 10 of 18 unrelated families (55.6%.) Among the 27 variants, 26 (96%) were heterozygous. A frameshift pathogenic variant, c.2643del, and one novel variant c.1366A>G were identified. Furthermore, seven variants with unknown clinical significance were detected: c.1158T>A, c.1346C>G, c.1174C>G, c.3630 G>T, c.3599A>T, and c.3400 G>C in exon 11, and c.5244T>A in exon 20. Six variants with conflicting pathogenicity interpretations, c. 3460T>A, c. 3572 G>A, c. 3700 G>C, c. 1246C>G, c. 1344C>G, and c. 1054 G>A, were also identified. Twelve benign/likely benign variants were identified. Rare BRCA1 variants that have not been reported in North Africa were found in Libyan patients. These findings provide preliminary insights into the BRCA1 variants that could contribute to hereditary BC risk in Libyans. Further functional, computational, and population analyses are essential to determine their significance and potential impact on BC risk, which could ultimately lead to more personalized management strategies.

Screening of interleukin 17F gene polymorphisms and eight subgingival pathogens in chronic periodontitis in Libyan patients.

Background: Chronic periodontitis (CP) is triggered by periodontal pathogens influenced by genetic and environmental factors. Recent studies have suggested that anti-inflammatory cytokines such as interleukin 17 (IL-17) play a prominent role in the pathogenesis of CP.Aim: This study aimed to investigate the association between eight sub-gingival pathogens and interleukin 17F (IL-17F) gene single nucleotide polymorphisms with CP among Libyans.Materials and Methods: A case-control study was conducted on 100 individuals between the ages of 25-65 years. Species-specific 16S rRNA primers for each pathogen were used in a multiplex PCR reaction to detect sub-gingival pathogens from a paper point sample. DNA was also extracted from buccal swab samples and IL-17F polymorphisms were detected by Sanger sequencing.Results: A highly significant association between the seven sub-gingival pathogens and CP, (p-value 0.0001) and a high prevalence of P. intermedia (100%), T. forsythia (96%), T. denticola and E. corrodens (92%), P. gingivalis (82%), C. rectus (74%), P. nigrescens (72%), A. actinomvcetcmcomitans (40%) were found in the case group compared with control group. A novel variant in the c. *34 G>A in IL-17F gene caused a change in glutamic amino acid to lysine amino acid, position on chromosome number (6) in the third exon, mRNA/genomic position 597, found in 14.6% of CP patients (p-value = 0.010) while the IL-17F (rs763780) SNP showed no association with CP (p-value = 0.334).Conclusion: P. intermedia appear as keystone pathogen for CP in the Libyan population. A novel variant in the IL-7F gene may be related to the severity of CP.

Whole-genome sequencing of SARS-COV-2 showed wide spread of B.1.525 in February 2021 in Libya.

Alpha (B.1.1.7) SARS-COV-2 variant was detected in September 2020 in minks and humans in Denmark and UK. This variant has several mutations in the spike region (S) which could increase the transmissibility of the virus 43-90% over previously circulating variants. The National Center for Disease Control (NCDC) announced on 24 February 2021 a 25% frequency of B.1.1.7 strain in Libya using a reverse-transcriptase quantitative PCR assay. This assay relies on the specific identification of the H69-V70 deletion in S gene which causes its failure of amplification (SGTF). This deletion is not specific for B.1.1.7, but is also characteristic of two other SARS-COV-2 variants. This study aimed to estimate the frequency of B.1.1.7 and identify other variants circulating in Libya in February 2021. We performed whole genome sequencing of 67 positive SARS-COV-2 samples collected on 25 February 2021 in Libya which were also tested by RT-qPCR for SGTF. Our results showed that 55% of samples had mutations specific to B.1.525 strain and only ~3% of samples belonged to B.1.1.7. These findings suggested that B.1.525 was spreading widely in Libya. The use of such RT-qPCR assay, although useful to track some variants, cannot discriminate between variants with H69-V70 deletion. RT-qPCR assays could be multiplexed to identify multiple variants and screen samples prior to sequencing. We emphasize on the need for providing whole-genome sequencing to the main COVID-19 diagnostic laboratories in Libya as well as establishing international collaboration for building capacity and advancing research in this time of the pandemic.