Genetic characterization of Callosciurus (Rodentia: Sciuridae) Asiatic squirrels introduced in Argentina

Squirrels have been traded in the pet market for several decades, and numerous species have established in the wild. The Asiatic species Callosciurus erythraeus and Callosciurus finlaysonii have been introduced into other parts of Asia, in Europe and South America. In this study, (1) we conducted a genetic characterization of C. erythraeus introduced into Argentina and compared them with native and introduced populations in Asia, and (2) we analyzed genetic variation among the four invasion foci in Argentina in order to corroborate that the pathway of invasion was a single introduction event in the country and subsequent translocations. We analyzed mitochondrial (cytochrome b, Cyt b; cytochrome oxidase c subunit I, COI and D-loop) and nuclear (recombination activating gene I, RAGI) DNA markers using the classical method (DNA barcoding gap analysis) and also the Automatic Barcode Gap Discovery method (ABGD). The markers D-loop, COI, and RAG1 indicated that the introduced squirrels from the different invasion foci formed a monophyletic group that, together with only one haplotype for the D-loop and COI markers, supported the hypothesis of one introduction event into Argentina followed by subsequent translocations. Unexpectedly, sequences from squirrels captured in Argentina were more related to C. finlaysonii than to C. erythraeus for D-loop and Cyt b markers. However, intraspecific variation among sequences of C. erythraeus belonging to different subspecies or collected in different regions was large and comparable with the distance to the sequences from Argentina. The ABGD method also indicated large genetic variability within C. erythraeus and close proximity between squirrels from Argentina and C. finlaysonii. The complex taxonomy of Callosciurus, as occurs with the sister species C. erythraeus and C. finlaysonii, requires a thorough systematic revision. A simultaneous analysis of diagnostic morphological characters and genetic markers is needed and will provide new insight regarding the worldwide invasion of Asiatic squirrels.Centro Regional de Estudios Genómico

Genetic characterization of Callosciurus (Rodentia: Sciuridae) Asiatic squirrels introduced in Argentina

Squirrels have been traded in the pet market for several decades, and numerous species have established in the wild. The Asiatic species Callosciurus erythraeus and Callosciurus finlaysonii have been introduced into other parts of Asia, in Europe and South America. In this study, (1) we conducted a genetic characterization of C. erythraeus introduced into Argentina and compared them with native and introduced populations in Asia, and (2) we analyzed genetic variation among the four invasion foci in Argentina in order to corroborate that the pathway of invasion was a single introduction event in the country and subsequent translocations. We analyzed mitochondrial (cytochrome b, Cyt b; cytochrome oxidase c subunit I, COI and D-loop) and nuclear (recombination activating gene I, RAGI) DNA markers using the classical method (DNA barcoding gap analysis) and also the Automatic Barcode Gap Discovery method (ABGD). The markers D-loop, COI, and RAG1 indicated that the introduced squirrels from the different invasion foci formed a monophyletic group that, together with only one haplotype for the D-loop and COI markers, supported the hypothesis of one introduction event into Argentina followed by subsequent translocations. Unexpectedly, sequences from squirrels captured in Argentina were more related to C. finlaysonii than to C. erythraeus for D-loop and Cyt b markers. However, intraspecific variation among sequences of C. erythraeus belonging to different subspecies or collected in different regions was large and comparable with the distance to the sequences from Argentina. The ABGD method also indicated large genetic variability within C. erythraeus and close proximity between squirrels from Argentina and C. finlaysonii. The complex taxonomy of Callosciurus, as occurs with the sister species C. erythraeus and C. finlaysonii, requires a thorough systematic revision. A simultaneous analysis of diagnostic morphological characters and genetic markers is needed and will provide new insight regarding the worldwide invasion of Asiatic squirrels.Centro Regional de Estudios Genómico

Genetic characterization of Callosciurus (Rodentia: Sciuridae) Asiatic squirrels introduced in Argentina

Squirrels have been traded in the pet market for several decades, and numerous species have established in the wild. The Asiatic species Callosciurus erythraeus and Callosciurus finlaysonii have been introduced into other parts of Asia, in Europe and South America. In this study, (1) we conducted a genetic characterization of C. erythraeus introduced into Argentina and compared them with native and introduced populations in Asia, and (2) we analyzed genetic variation among the four invasion foci in Argentina in order to corroborate that the pathway of invasion was a single introduction event in the country and subsequent translocations. We analyzed mitochondrial (cytochrome b, Cyt b; cytochrome oxidase c subunit I, COI and D-loop) and nuclear (recombination activating gene I, RAGI) DNA markers using the classical method (DNA barcoding gap analysis) and also the Automatic Barcode Gap Discovery method (ABGD). The markers D-loop, COI, and RAG1 indicated that the introduced squirrels from the different invasion foci formed a monophyletic group that, together with only one haplotype for the D-loop and COI markers, supported the hypothesis of one introduction event into Argentina followed by subsequent translocations. Unexpectedly, sequences from squirrels captured in Argentina were more related to C. finlaysonii than to C. erythraeus for D-loop and Cyt b markers. However, intraspecific variation among sequences of C. erythraeus belonging to different subspecies or collected in different regions was large and comparable with the distance to the sequences from Argentina. The ABGD method also indicated large genetic variability within C. erythraeus and close proximity between squirrels from Argentina and C. finlaysonii. The complex taxonomy of Callosciurus, as occurs with the sister species C. erythraeus and C. finlaysonii, requires a thorough systematic revision. A simultaneous analysis of diagnostic morphological characters and genetic markers is needed and will provide new insight regarding the worldwide invasion of Asiatic squirrels.Centro Regional de Estudios Genómico

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.Fil: Vaccaro, Carlos Alberto. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: López Kostner, Francisco. No especifíca;Fil: Adriana, Della Valle. Hospital Fuerzas Armadas; UruguayFil: Inez Palmero, Edenir. Hospital de cáncer de Barretos, FACISB; BrasilFil: Rossi, Benedito Mauro. Hospital Sirio Libanes; BrasilFil: Antelo, Marina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina. Universidad Nacional de Lanús; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Carraro, Dirce Maria. No especifíca;Fil: Forones, Nora Manoukian. Universidade Federal de Sao Paulo; BrasilFil: Bohorquez, Mabel. Universidad del Tolima; ColombiaFil: Lino Silva, Leonardo S.. Instituto Nacional de Cancerologia; MéxicoFil: Buleje, Jose. Universidad de San Martín de Porres; PerúFil: Spirandelli, Florencia. No especifíca;Fil: Abe Sandes, Kiyoko. Universidade Federal da Bahia; BrasilFil: Nascimento, Ivana. No especifíca;Fil: Sullcahuaman, Yasser. Universidad Peruana de Ciencias Aplicadas; Perú. Instituto de Investigación Genomica; PerúFil: Sarroca, Carlos. Hospital Fuerzas Armadas; UruguayFil: Gonzalez, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Herrando, Alberto Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Alvarez, Karin. No especifíca;Fil: Neffa, Florencia. Hospital Fuerzas Armadas; UruguayFil: Galvão, Henrique Camposreis. Barretos Cancer Hospital; BrasilFil: Esperon, Patricia. Hospital Fuerzas Armadas; UruguayFil: Golubicki, Mariano. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Cisterna, Daniel. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Cardoso, Florencia C.. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Tardin Torrezan, Giovana. No especifíca;Fil: Aguiar Junior, Samuel. No especifíca;Fil: Aparecida Marques Pimenta, Célia. Universidade Federal de Sao Paulo; BrasilFil: Nirvana da Cruz Formiga, María. No especifíca;Fil: Santos, Erika. Hospital Sirio Libanes; BrasilFil: Sá, Caroline U.. Hospital Sirio Libanes; BrasilFil: Oliveira, Edite P.. Hospital Sirio Libanes; BrasilFil: Fujita, Ricardo. Universidad de San Martín de Porres; PerúFil: Spirandelli, Enrique. No especifíca;Fil: Jimenez, Geiner. No especifíca;Fil: Santa Cruz Guindalini, Rodrigo. Universidade de Sao Paulo; BrasilFil: Gondim Meira Velame de Azevedo, Renata. No especifíca;Fil: Souza Mario Bueno, Larissa. Universidade Federal da Bahia; BrasilFil: dos Santos Nogueira, Sonia Tereza. No especifíca;Fil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentin

SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study.

BACKGROUND: SARS-CoV-2 lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. METHODS: We collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16 November 2020 to 10 January 2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. FINDINGS: Sequences were obtained from 2341 inpatients (HOCI cases=786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The HR for mortality of B.1.1.7 compared with other lineages was 1.01 (95% CI 0.79 to 1.28, p=0.94) and for ITU admission was 1.01 (95% CI 0.75 to 1.37, p=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95 to 1.78, p=0.096) and ITU admission (HR 1.82, 95% CI 1.15 to 2.90, p=0.011) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61 to 1.10, p=0.177; ITU HR 0.74, 95% CI 0.52 to 1.04, p=0.086). INTERPRETATION: In common with smaller studies of patients hospitalised with SARS-CoV-2, we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared with other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.This report was produced by members of the COG-UK-HOCI Variant substudy consortium. COG-UK-HOCI is part of COG-UK. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute

BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population

Abstract Background Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. Results A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients. Conclusions In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment

BRCA1 and BRCA2 Mutations Other Than the Founder Alleles Among Ashkenazi Jewish in the Population of Argentina

In Ashkenazi Jewish (AJ) high risk families 3 mutations [2 in BRCA1 (c. 68_69del and c.5266dup) and 1 in BRCA2 (c.5946del)] account for the majority of high risk breast and ovarian cancer cases in that ethnic group. Few studies with limited number of genotyped individuals have expanded the spectrum of mutations in both BRCA genes beyond the 3 mutation panel. In this study, 279 high risk individual AJ were counseled at CEMIC (Centro de Educación Médica e Investigaciones Clínicas), and were genotyped first for the 3 recurrent mutation panel followed by Next Generation Sequencing (NGS) of BRCA1 BRCA2 in 76 individuals who tested negative for the first genotyping step. Of 279 probands (259 women), 55 (50 women) harbored one of the 3 mutations (19.7%); Of 76 fully sequenced cases (73 women), 6 (5 women) (7.9%) carried a pathogenic mutation: in BRCA1, c.2728C>T - p.(Gln910*); c.5407-?_(*1_?)del and c.5445G>A - p.(Trp1815*); in BRCA2, c.5351dup - p.(Asn1784Lysfs*3); c.7308del - p.(Asn2436Lysfs*33) and c.9026_9030del - p.(Tyr3009Serfs*7). Of 61 mutation carriers the distribution was as follows: 11 cancer free at the time of genotyping, 34 female breast cancer cases with age range 28–72 years (41.6 ± 9.3), 3 male breast cancer cases with age range 59–75 years (65 ± 7.3), 6 breast and ovarian cancer cases with age range 35–60 years (breast 40.4 ± 5.2; ovary 47.8 ± 7.2) and 7 ovarian cancer cases with age range 41–77 years (60.6 ± 13.3). This information proved highly useful for counseling, treatment, and prevention for the patient and the family. In conclusion comprehensive BRCA1/2 testing in AJ high risk breast ovarian cancer cases adds valuable clinically relevant information in a subset of cases estimated up to 7% and is therefore recommended

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency