Genetic Distribution of Five Spinocerebellar Ataxia Microsatellite Loci in Mexican Native American Populations and Its Impact on Contemporary Mestizo Populations

Spinocerebellar ataxias (SCAs) conform a heterogeneous group of neurodegenerative disorders with autosomal dominant inheritance. Five of the most frequent SCAs are caused by a CAG repeat expansion in the exons of specific genes. The SCAs incidence and the distribution of polymorphic CAG alleles vary among populations and ethnicities. Thus, characterization of the genetic architecture of ethnically diverse populations, which have undergone recent admixture and demographic events, could facilitate the identification of genetic risk factors. Owing to the great ethnic diversity of the Mexican population, this study aimed to analyze the allele frequencies of five SCA microsatellite loci (SCA1, SCA2, SCA3, SCA6, and SCA7) in eleven Mexican Native American (MNA) populations. Data from the literature were used to compare the allelic distribution of SCA loci with worldwide populations. The SCA loci allelic frequencies evidenced a certain genetic homogeneity in the MNA populations, except for Mayans, who exhibited distinctive genetic profiles. Neither pathological nor large normal alleles were found in MNA populations, except for the SCA2 pre-mutated allele in the Zapotec population. Collectively, our findings demonstrated the contribution of the MNA ancestry in shaping the genetic structure of contemporary Mexican Mestizo populations. Our results also suggest that Native American ancestry has no impact on the origin of SCAs in the Mexican population. Instead, the acquisition of pathological SCA alleles could be associated with European migration.

Genetic profiles and invasion ability of Listeria monocytogenes isolated from bovine carcasses in Southern Brazil

The goals of this study were to evaluate the persistence and the virulence potential of Listeria monocytogenes isolated from beef carcasses obtained in processing facilities in the Southern region of Rio Grande do Sul, Brazil, based on pulsed field gel electrophoresis (PFGE), invasion ability in human colorectal carcinoma cells (HCT-116), InlA expression by western blot (WB) and identification of mutation points in the inlA . PFGE profiles demonstrated that L. monocytogenes isolates were grouped based on their previously identified lineages and serogroups (lineage I: serogroups IIb, n = 2, and IVb, n = 5; lineage II, serogroup IIc, n = 5), isolates with indistinguishable genetic profiles by this method were obtained from different slaughterhouses and sampling steps, with up to 3-year interval. Seven isolates showed high invasion ability (2.4 to 7.4%, lineage I, n = 6, lineage II, n = 1) in HCT and expressed InlA. Five isolates showed low cell invasion ability (0.6 to 1.4%, lineage I, n = 1, lineage II, n = 4) and did not express InlA, and two of them (lineage II, serogroup IIc) presented mutations in inlA leading to a premature stop codon (PMSC) type 19, at position 326 (GAA → TAA). The results demonstrated that most of L. monocytogenes isolates from Lineage I expressed InlA and were the most invasive in HCT indicating their high virulence potential, while most isolates from Lineage II showed attenuated invasion due to non-expression of InlA and the presence of PMSC type 19 in inlA . The obtained results demonstrated that L. monocytogenes with indistinguishable PFGE profiles can be persisting or being reintroduced in beef processing facilities in the studied region and differences on their virulence potential based on their lineages and serogroups.

Principles of Spatial Transcriptomics Analysis: A Practical Walk-Through in Kidney Tissue

Spatial transcriptomic technologies capture genome-wide readouts across biological tissue space. Moreover, recent advances in this technology, including Slide-seqV2, have achieved spatial transcriptomic data collection at a near-single cell resolution. To-date, a repertoire of computational tools has been developed to discern cell type classes given the transcriptomic profiles of tissue coordinates. Upon applying these tools, we can explore the spatial patterns of distinct cell types and characterize how genes are spatially expressed within different cell type contexts. The kidney is one organ whose function relies upon spatially defined structures consisting of distinct cellular makeup. Thus, the application of Slide-seqV2 to kidney tissue has enabled us to elucidate spatially characteristic cellular and genetic profiles at a scale that remains largely unexplored. Here, we review spatial transcriptomic technologies, as well as computational approaches for cell type mapping and spatial cell type and transcriptomic characterizations. We take kidney tissue as an example to demonstrate how the technologies are applied, while considering the nuances of this architecturally complex tissue.

mecA positive Staphylococcus spp. in bovine mastitis, milkers, milking environment, and the circulation of different MRSA clones at dairy cows farms in the Northeast region of Brazil

ABSTRACT: This study detected the presence and distribution of mecA in Staphylococcus spp. in the dairy production environment at farm level in Brazil. We analyzed 335 samples of mastitis cow milk, 15 samples of nostrils and hand swabs from milkers, 14 teat cup swabs, and 9 milking buckets swabs. Initially, the samples were subjected to microbiological analysis to detect Staphylococcus spp. and then S. aureus and mecA positive isolates were identified by PCR. All S. aureus isolates carrying the mecA genes were subjected to DNA macro-restriction analysis by Pulsed-Field Gel Electrophoresis (PFGE). The mecA gene was detected in 6/335 (1.78%) of mastitis cow milk, 5/15 (33.3%), and 5/15 (33.3%) of nostrils and hand swab, and 4/14 (28.5%) of the teat cup isolates. MRSA genotyping was performed by PFGE, a total of seven pulsotypes were grouped in two clusters. This study identified the occurrence and spread of MRSA at dairy environment of farms, and also the existence of distinct genetic profiles between isolates.

Ultrasensitive analysis of genetic instability related to chemical exposure

Our concerns have been raised about whether prolonged exposure to ammunition-related chemicals could correlate with genomic instability predisposing to lung carcinogenesis. The group of professional soldiers engaged in routine ammunition analysis and its explosive properties testing. To assess the presence of an innate genetic profile, DNA isolated from swabs was analyzed with LungCarta and HS Lung Panels and MassARRAY Analyzer 4 mass spectrometry. The presence of new somatic single nucleotide polymorphisms (SNPs) was detected with liquid biopsy technique and circulating cell-free DNA (ccfDNA) isolation, which was further analyzed with UltraSeek Lung Panel. Both genetic profiles obtained for each individual were compared. Genetic analysis revealed that in professional soldiers with long-term exposure to ammunition-related toxic chemicals, new SNPs in genes related to lung carcinogenesis are present. The preliminary data indicate that using modern molecular techniques could be a valuable tool for monitoring the genome instability in context of occupational risk of harmful volatile toxic compounds and improving personnel safety. The analyzed group will be further enlarged, and follow-up studies will be continued.

Genetic Profiles and Risk Stratification in Adult De Novo Acute Myeloid Leukaemia in Relation to Age, Gender, and Ethnicity: A Study from Malaysia

Hitherto, no data describing the heterogeneity of genetic profiles and risk stratifications of adult acute myeloid leukaemia (AML) in Southeast Asia are reported. This study assessed genetic profiles, Moorman’s hierarchical classification, and ELN 2017-based risk stratifications in relation to age, gender, and ethnicity in Malaysian adult AML patients. A total of 854 AML patients: male (52%), female (48%) were recruited comprising three main ethnic groups: Malays (59%), Chinese (32%) and Indians (8%). Of 307 patients with abnormal karyotypes: 36% exhibited translocations; 10% deletions and 5% trisomies. The commonest genotype was FLT3-ITD-NPM1wt (276/414; 66.7%). ELN 2017 risk stratification was performed on 494 patients, and 41% were classified as favourable, 39% as intermediate and 20% as adverse groups. More females (47%) were in the favourable risk group compared to males (37%), whereas adverse risk was higher in patients above 60 (24%) of age compared to below 60 (18%) patients. We observed heterogeneity in the distribution of genetic profiles and risk stratifications between the age groups and gender, but not among the ethnic groups. Our study elucidated the diversity of adult AML genetic profiles between Southeast Asians and other regions worldwide.

Genetic profiles of three Cinchona species in Junghuhn Natural Reserve, Indonesia

Cinchona species were widely used as ancient medicines for different diseases because they contain the active component quinine and its derivatives. However, studies on the molecular aspects of cinchona, including its genetic diversity, have not been reported because most previous works focused on the administration of the antimalarial cinchona alkaloid. Quinine is also being tested as alternative compound for the treatment of Covid-19. The Junghuhn Natural Reserve in Indonesia contains three different types of cinchona plants, namely, Cinchona calisaya, Cinchona pubescens, and Cinchona sp. Given that the genetic diversity and kinship of these species have never been studied, collecting data on the cinchona gene pool has become imperative. This study analyzed the genetic diversity of the cinchona species in the Junghuhn Natural Reserve, Indonesia, by using eight RAPD markers, i.e., OPA-2, OPA-9, OPB-02, OPB-03, OPB-04, OPB-05, OPB-7, and OPJ-07, during 2020 at the University of Jenderal Soedirman, Purwokerto-Indonesia. Polymorphic band data were obtained. Then, phenogram analysis was conducted by using UPGMA and maximum parsimony with MEGA7. The RAPD profiles of Cinchona species (C. calisaya, C. pubescent, and Cinchona sp.) revealed polymorphism with different markers, i.e., OPA-2 (90%), OPB-2 (75%), OPB-5 (75%), OPB-3 (66.66%), OPB-4 (66.66%), OPB-7 (66.66%), OPJ-7 (66.66%), and OPA-9 (58.33%) sequentially with total polymorphism (70.62%). C. calisaya was identified as the most distinctive species. UPGMA yielded a coefficient of 0.200 and two distinctive groups: Group I, which comprised C. pubescens and Cinchona sp. with the p-distance value of 0.333, and Group II, which contained C. calisaya. Ixora sp. was treated as an outgroup plant. The topology of the dendrogram was consistent with that of the UPGMA dendrogram. Results may be used for the further exploration of the genetic diversity of cinchona species.

Molecular Pathology of Human Papilloma Virus-Negative Cervical Cancers

Cervical cancer is the fourth most common cancer in women worldwide and is predominantly caused by infection with human papillomavirus (HPV). However, a small subset of cervical cancers tests negative for HPV, including true HPV-independent cancers and false-negative cases. True HPV-negative cancers appear to be more prevalent in certain pathological adenocarcinoma subtypes, such as gastric- and clear-cell-type adenocarcinomas. Moreover, HPV-negative cervical cancers have proven to be a biologically distinct tumor subset that follows a different pathogenetic pathway to HPV-associated cervical cancers. HPV-negative cervical cancers are often diagnosed at an advanced stage with a poor prognosis and are expected to persist in the post-HPV vaccination era; therefore, it is important to understand HPV-negative cancers. In this review, we provide a concise overview of the molecular pathology of HPV-negative cervical cancers, with a focus on their definitions, the potential causes of false-negative HPV tests, and the histology, genetic profiles, and pathogenesis of HPV-negative cancers.

GiPS: Genomics-informed parent selection uncovers the breeding value of wheat genetic resources

The great efforts spent in the maintenance of past diversity in genebanks are rationalized by the potential role of plant genetic resources in future crop improvement: a concept whose practical implementation has fallen short of expectations. Here, we implement genomics-informed parent selection to expedite pre-breeding without discriminating against non-adapted germplasm. We collect dense genetic profiles for a large winter wheat collection and evaluate grain yield and resistance to yellow rust in representative coresets. Genomic prediction within and across genebanks identified the best parents for PGR x elite derived crosses that outyielded current elite cultivars in multiple field trials.

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Breast cancer (BC) is the leading cause of death among female patients with cancer. Patients with triple-negative breast cancer (TNBC) have the lowest survival rate. TNBC has substantial heterogeneity within the BC population. This study utilized our novel patient stratification and drug repositioning method to find subgroups of BC patients that share common genetic profiles and that may respond similarly to the recommended drugs. After further examination of the discovered patient subgroups, we identified five homogeneous druggable TNBC subgroups. A drug repositioning algorithm was then applied to find the drugs with a high potential for each subgroup. Most of the top drugs for these subgroups were chemotherapy used for various types of cancer, including BC. After analyzing the biological mechanisms targeted by these drugs, ferroptosis was the common cell death mechanism induced by the top drugs in the subgroups with neoplasm subdivision and race as clinical variables. In contrast, the antioxidative effect on cancer cells was the common targeted mechanism in the subgroup of patients with an age less than 50. Literature reviews were used to validate our findings, which could provide invaluable insights to streamline the drug repositioning process and could be further studied in a wet lab setting and in clinical trials.