Molecular identification of whales remains from the Keller Peninsula, Admiralty Bay, King George Island, Antarctica.

At the beginning of the 20th century, intense whaling activity took place in the South Shetland Islands, which is represented today in the form of ruins and numerous whale bones scattered along several Antarctic beaches. Despite being exposed to a harsh environment throughout the last decades, the present manuscript tried to answer if these bone remains still have viable DNA to allow species' identification using molecular methods. Several individuals were collected from the shores of Keller Peninsula, Admiralty Bay, Antarctica, and submitted to DNA extraction, amplification and Sanger sequencing. The challenging identification of these bone fragments proved to be still feasible. Mitochondrial DNA was successfully extracted, amplified and sequenced. A database with 43 sequences including previously published and newly determined sequences were built and enabled the precise identification to species level for some of the collected samples, therefore shedding light on the whales species that inhabited the region and how their overexploitation seems to have affected modern day presence of these species within the study area.

Integrating frontiers: a holistic, quantum and evolutionary approach to conquering cancer through systems biology and multidisciplinary synergy.

Cancer therapy is facing increasingly significant challenges, marked by a wide range of techniques and research efforts centered around somatic mutations, precision oncology, and the vast amount of big data. Despite this abundance of information, the quest to cure cancer often seems more elusive, with the "war on cancer" yet to deliver a definitive victory. A particularly pressing issue is the development of tumor treatment resistance, highlighting the urgent need for innovative approaches. Evolutionary, Quantum Biology and System Biology offer a promising framework for advancing experimental cancer research. By integrating theoretical studies, translational methods, and flexible multidisciplinary clinical research, there's potential to enhance current treatment strategies and improve outcomes for cancer patients. Establishing stronger links between evolutionary, quantum, entropy and chaos principles and oncology could lead to more effective treatments that leverage an understanding of the tumor's evolutionary dynamics, paving the way for novel methods to control and mitigate cancer. Achieving these objectives necessitates a commitment to multidisciplinary and interprofessional collaboration at the heart of both research and clinical endeavors in oncology. This entails dismantling silos between disciplines, encouraging open communication and data sharing, and integrating diverse viewpoints and expertise from the outset of research projects. Being receptive to new scientific discoveries and responsive to how patients react to treatments is also crucial. Such strategies are key to keeping the field of oncology at the forefront of effective cancer management, ensuring patients receive the most personalized and effective care. Ultimately, this approach aims to push the boundaries of cancer understanding, treating it as a manageable chronic condition, aiming to extend life expectancy and enhance patient quality of life.

Impact of patrilocality on contrasting patterns of paternal and maternal heritage in Central-West Africa.

Despite their ancient past and high diversity, African populations are the least represented in human population genetic studies. In this study, uniparental markers (mtDNA and Y chromosome) were used to investigate the impact of sociocultural factors on the genetic diversity and inter-ethnolinguistic gene flow in the three major Nigerian groups: Hausa (n = 89), Yoruba (n = 135) and Igbo (n = 134). The results show a distinct history from the maternal and paternal perspectives. The three Nigerian groups present a similar substrate for mtDNA, but not for the Y chromosome. The two Niger-Congo groups, Yoruba and Igbo, are paternally genetically correlated with populations from the same ethnolinguistic affiliation. Meanwhile, the Hausa is paternally closer to other Afro-Asiatic populations and presented a high diversity of lineages from across Africa. When expanding the analyses to other African populations, it is observed that language did not act as a major barrier to female-mediated gene flow and that the differentiation of paternal lineages is better correlated with linguistic than geographic distances. The results obtained demonstrate the impact of patrilocality, a common and well-established practice in populations from Central-West Africa, in the preservation of the patrilineage gene pool and in the affirmation of identity between groups.

Microsatellites' mutation modeling through the analysis of the Y-chromosomal transmission: Results of a GHEP-ISFG collaborative study.

The Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) organized a collaborative study on mutations of Y-chromosomal short tandem repeats (Y-STRs). New data from 2225 father-son duos and data from 44 previously published reports, corresponding to 25,729 duos, were collected and analyzed. Marker-specific mutation rates were estimated for 33 Y-STRs. Although highly dependent on the analyzed marker, mutations compatible with the gain or loss of a single repeat were 23.2 times more likely than those involving a greater number of repeats. Longer alleles (relatively to the modal one) showed to be nearly twice more mutable than the shorter ones. Within the subset of longer alleles, the loss of repeats showed to be nearly twice more likely than the gain. Conversely, shorter alleles showed a symmetrical trend, with repeat gains being twofold more frequent than reductions. A positive correlation between the paternal age and the mutation rate was observed, strengthening previous findings. The results of a machine learning approach, via logistic regression analyses, allowed the establishment of algebraic formulas for estimating the probability of mutation depending on paternal age and allele length for DYS389I, DYS393 and DYS627. Algebraic formulas could also be established considering only the allele length as predictor for DYS19, DYS389I, DYS389II-I, DYS390, DYS391, DYS393, DYS437, DYS439, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS533, DYS576, DYS626 and DYS627 loci. For the remaining Y-STRs, a lack of statistical significance was observed, probably as a consequence of the small effective size of the subsets available, a common difficulty in the modeling of rare events as is the case of mutations. The amount of data used in the different analyses varied widely, depending on how the data were reported in the publications analyzed. This shows a regrettable waste of produced data, due to inadequate communication of the results, supporting an urgent need of publication guidelines for mutation studies.

Analysis of 12 X-STRs loci in a population from southeastern Brazil.

Short tandem repeat (STR) markers on the X chromosome have a high potential for solving complex kinship analysis and individual identification cases. To achieve such purposes, allele and haplotype frequencies for the specific population are necessary. Nonetheless, such frequencies are not always available. Therefore, we obtained haplotypes from 520 unrelated males from four different geographic regions of Espírito Santo - Brazil, using the Investigator Argus X-12 kit. Forensic parameters for linked groups of four X-STR loci are reported. Genetic distance analyzes suggest that ES population is genetically closer to the Italian population and farther from the Mexican one, among the populations analyzed in this study.

Prognostic Factors and Markers in Non-Small Cell Lung Cancer: Recent Progress and Future Challenges.

Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting.

Biomarkers in Breast Cancer: An Old Story with a New End.

Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, prognosis, and risk prediction, enabling personalized treatments, improving therapy, and preventing overtreatment, undertreatment, and incorrect treatment. Several breast cancer biomarkers have been identified and, along with traditional biomarkers, they can assist physicians throughout treatment plan and increase therapy success. Despite the need of more data to improve specificity and determine the real clinical utility of some biomarkers, others are already established and can be used as a guide to make treatment decisions. In this review, we summarize the available traditional, novel, and potential biomarkers while also including gene expression profiles, breast cancer single-cell and polyploid giant cancer cells. We hope to help physicians understand tumor specific characteristics and support decision-making in patient-personalized clinical management, consequently improving treatment outcome.

Computational Biology Helps Understand How Polyploid Giant Cancer Cells Drive Tumor Success.

Precision and organization govern the cell cycle, ensuring normal proliferation. However, some cells may undergo abnormal cell divisions (neosis) or variations of mitotic cycles (endopolyploidy). Consequently, the formation of polyploid giant cancer cells (PGCCs), critical for tumor survival, resistance, and immortalization, can occur. Newly formed cells end up accessing numerous multicellular and unicellular programs that enable metastasis, drug resistance, tumor recurrence, and self-renewal or diverse clone formation. An integrative literature review was carried out, searching articles in several sites, including: PUBMED, NCBI-PMC, and Google Academic, published in English, indexed in referenced databases and without a publication time filter, but prioritizing articles from the last 3 years, to answer the following questions: (i) "What is the current knowledge about polyploidy in tumors?"; (ii) "What are the applications of computational studies for the understanding of cancer polyploidy?"; and (iii) "How do PGCCs contribute to tumorigenesis?"

Correction: Association of NOD2 and IFNG single nucleotide polymorphisms with leprosy in the Amazon ethnic admixed population.

[This corrects the article DOI: 10.1371/journal.pntd.0008247.].

Translational Bioinformatics Applied to the Study of Complex Diseases.

Translational Bioinformatics (TBI) is defined as the union of translational medicine and bioinformatics. It emerges as a major advance in science and technology by covering everything, from the most basic database discoveries, to the development of algorithms for molecular and cellular analysis, as well as their clinical applications. This technology makes it possible to access the knowledge of scientific evidence and apply it to clinical practice. This manuscript aims to highlight the role of TBI in the study of complex diseases, as well as its application to the understanding and treatment of cancer. An integrative literature review was carried out, obtaining articles through several websites, among them: PUBMED, Science Direct, NCBI-PMC, Scientific Electronic Library Online (SciELO), and Google Academic, published in English, Spanish, and Portuguese, indexed in the referred databases and answering the following guiding question: "How does TBI provide a scientific understanding of complex diseases?" An additional effort is aimed at the dissemination, inclusion, and perpetuation of TBI knowledge from the academic environment to society, helping the study, understanding, and elucidating of complex disease mechanics and their treatment.

Tierra Del Fuego: What Is Left from the Precolonial Male Lineages?

Similar to other South American regions, Tierra del Fuego has an admixed population characterized by distinct ancestors: Native Americans who first occupied the continent, European settlers who arrived from the late 15th century onwards, and Sub-Saharan Africans who were brought to the Americas for slave labor. To disclose the paternal lineages in the current population from Tierra del Fuego, 196 unrelated males were genotyped for 23 Y-STRs and 52 Y-SNPs. Haplotype and haplogroup diversities were high, indicating the absence of strong founder or drift events. A high frequency of Eurasian haplogroups was detected (94.4%), followed by Native American (5.1%) and African (0.5%) ones. The haplogroup R was the most abundant (48.5%), with the sub-haplogroup R-S116* taking up a quarter of the total dataset. Comparative analyses with other Latin American populations showed similarities with other admixed populations from Argentina. Regarding Eurasian populations, Tierra del Fuego presented similarities with Italian and Iberian populations. In an in-depth analysis of the haplogroup R-M269 and its subtypes, Tierra del Fuego displayed a close proximity to the Iberian Peninsula. The results from this study are in line with the historical records and reflect the severe demographic change led mainly by male newcomers with paternal European origin.

Testing the Ion AmpliSeq™ HID Y-SNP Research Panel v1 for performance and resolution in admixed South Americans of haplogroup Q.

Y haplogroups, defined by Y-SNPs, allow the reconstruction of the human Y chromosome genealogy, which is important for population, evolutionary and forensic genetics. In this study, Y-SNPs were typed and haplogroups inferred with the MPS Ion AmpliSeq™ HID Y-SNP Research Panel v1, as a high-throughput approach. Firstly, the performance of the panel was evaluated with different DNA input amounts, reagent volumes and cycle numbers. DNA-inputs from 0.5 to 1 ng generated the most balanced read depth. Combined with full reagent and 19 cycles, this offered the highest number of amplicons with a sequencing read depth of at least 20 reads. Secondly, the sub-haplogroups of 182 admixed South Americans and Greenlanders belonging to haplogroup Q were inferred and tested for potential improvement in resolution. Most samples were assigned to lineage Q-M3 with some samples assigned to lineages upstream (Q-M346, L56, L57; Q-L331, L53; Q-L54; Q-CTS11969, CTS11970) or parallel (Q-L330, L334; Q-Z780/M971) to Q-M3. Only one sample was assigned to a downstream lineage (Q-Z35615, Z35616). Most individuals of haplogroup Q with NAM ancestry could neither be distinguished from each other, nor from half of the Greenlandic samples. Typing additional, known SNPs within lineage Q-M3, Z19483 and SA05, increased the resolution of predicted haplogroups. The search for novel variants in the sequenced regions allowed the detection of 42 variants and the subdivision of lineage Q-M3 into new subclades. The variants found in six of these subclades were exclusive to certain South American countries. In light of the limited differentiation of haplogroup Q samples, the additional information on known or novel SNPs disclosed in this study when using MPS Ion AmpliSeq™ HID Y-SNP Research Panel v1 should be included in the Yleaf software, to increase the differentiation of lineage Q-M3.

Uniparental genetic markers to investigate hybridization in wild-born marmosets with a mixed phenotype among Callithrix aurita and invasive species.

The native marmoset of the Southeastern Atlantic Forest in Brazil is among the 25 most endangered primates of the world. Hybridization with alien species is one of its main threats registered since the early 2000s based on phenotype, so far, without genetic confirmation. Using uniparental molecular markers, we analyzed 18 putative hybrids, captured from 2004 to 2013 in different localities of the Atlantic Forest. A nine base pair deletion in the SRY gene of C. aurita was used to investigate paternal ancestry. Maternal ancestry was assessed by DNA sequencing of ca. 455 bp from the COX2 gene. Hybridization was confirmed for 16 out of the 18 marmosets since they inherited COX2 haplotypes of the alien C. penicillata or C. jacchus and the SRY deletion specific to C. aurita. Two individuals inherited both parental lineages of C. aurita, which is probably related to backcrossing or hybrid interbreeding. The direction of hybridization of females with the matrilineal lineage of invasive species with males descending from the native lineage was predominant in our sampling. This is the first time that hybridization between C. aurita and invasive species has been confirmed through genetic analysis.

Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

Host factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. Here, we accessed samples from 153 pregnant women (77 without and 76 with CZS) and 143 newborns (77 without and 66 with CZS) exposed to ZIKV conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS outcome, and characterized placenta gene expression profile at term. Newborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.41; IC=1.35-8.60; Pcorrected=0.032). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. We found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. Despite of the low sample size se findings shed light on the host-pathogen interaction focusing on the genetically regulated type I/type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections.

The Ancestry of Eastern Paraguay: A Typical South American Profile with a Unique Pattern of Admixture.

Immigrants from diverse origins have arrived in Paraguay and produced important demographic changes in a territory initially inhabited by indigenous Guarani. Few studies have been performed to estimate the proportion of Native ancestry that is still preserved in Paraguay and the role of females and males in admixture processes. Therefore, 548 individuals from eastern Paraguay were genotyped for three marker sets: mtDNA, Y-SNPs and autosomal AIM-InDels. A genetic homogeneity was found between departments for each set of markers, supported by the demographic data collected, which showed that only 43% of the individuals have the same birthplace as their parents. The results show a sex-biased intermarriage, with higher maternal than paternal Native American ancestry. Within the native mtDNA lineages in Paraguay (87.2% of the total), most haplogroups have a broad distribution across the subcontinent, and only few are concentrated around the Paraná River basin. The frequency distribution of the European paternal lineages in Paraguay (92.2% of the total) showed a major contribution from the Iberian region. In addition to the remaining legacy of the colonial period, the joint analysis of the different types of markers included in this study revealed the impact of post-war migrations on the current genetic background of Paraguay.

Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations.

Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this case-control study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus-North; Salvador-Northeast; Rondonópolis-Midwest and Rio de Janeiro-Southeast) and with tuberculosis in Mozambique. Haplotype T/G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 -recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima's D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.

Putative pathogen-selected polymorphisms in the PKLR gene are associated with mycobacterial susceptibility in Brazilian and African populations

Investigation of human genes under pathogen-driven selection as Plasmodium sp. has pinpointed genetic variants that participate in the adaptation to the environment and/or are related to severities of human diseases. The current study examined an example of an evolutionary trade-off in which genetic variants in the PKLR gene putatively selected for malaria resistance influence the susceptibility to mycobacterial diseases (leprosy and tuberculosis) in Brazilian population and Mozambique. A complete characterization of the biological effect of those risk variants may clarify the role of the PKLR gene in leprosy and tuberculosis. Deciphering the genetic basis of mycobacterial diseases has implications for the identification of true high-risk individuals in order to optimize screening strategies. Furthermore, the trade-off mechanism discussed in this work might occur in other central genes of immune response and biochemical pathways, controlling the susceptibility to other infectious diseases.

Patterns of genetic diversity in Colombia for 38 indels used in human identification.

The current population of Colombia has a genetic heterogeneity resulting from different migrations from other continents and within the country. In addition, there are small groups in their territory that have remained isolated and therefore have a different genetic pool in relation to that of the neighbouring urban populations. This population stratification must be considered in forensic analysis, being more complex for markers with marked intercontinental differentiation. In this study, population differentiation in Colombian admixed, native, and Afro-descendant populations was evaluated for a group of 38 indels described for forensic use. Allelic frequencies and parameters of forensic relevance were determined in each of the groups defined based on population differentiation analyses. In addition to the differences found between population groups, the results show that the set of 38 indels analysed could be useful in studies of individual identification in Colombia. The exclusion power presented by this set of markers suggests the need for joint use with other markers, being able to complement the STRs in paternity cases. High levels of both power of discrimination and exclusion were found when complementing the 38 HID-indels with a second multiplex, for a total of 83 indels.

Searching for the roots of the first free African American community.

San Basilio de Palenque is an Afro-descendant community near Cartagena, Colombia, founded in the sixteenth century. The recognition of the historical and cultural importance of Palenque has promoted several studies, namely concerning the African roots of its first inhabitants. To deepen the knowledge of the origin and diversity of the Palenque parental lineages, we analysed a sample of 81 individuals for the entire mtDNA Control Region as well as 92 individuals for 27 Y-STRs and 95 for 51 Y-SNPs. The results confirmed the strong isolation of the Palenque, with some degree of influx of Native American maternal lineages, and a European admixture exclusively mediated by men. Due to the high genetic drift observed, a pairwise FST analysis with available data on African populations proved to be inadequate for determining population affinities. In contrast, when a phylogenetic approach was used, it was possible to infer the phylogeographic origin of some lineages in Palenque. Contradicting previous studies indicating a single African origin, our results evidence parental genetic contributions from widely different African regions.

Evaluation of the Precision of Ancestry Inferences in South American Admixed Populations.

Ancestry informative markers (AIMs) are used in forensic genetics to infer biogeographical ancestry (BGA) of individuals and may also have a prominent role in future police and identification investigations. In the last few years, many studies have been published reporting new AIM sets. These sets include markers (usually around 100 or less) selected with different purposes and different population resolutions. Regardless of the ability of these sets to separate populations from different continents or regions, the uncertainty associated with the estimates provided by these panels and their capacity to accurately report the different ancestral contributions in individuals of admixed populations has rarely been investigated. This issue is addressed in this study by evaluating different AIM sets. Ancestry inference was carried out in admixed South American populations, both at population and individual levels. The results of ancestry inferences using AIM sets with different numbers of markers among admixed reference populations were compared. To evaluate the performance of the different ancestry panels at the individual level, expected and observed estimates among families and their offspring were compared, considering that (1) the apportionment of ancestry in the offspring should be closer to the average ancestry of the parents, and (2) full siblings should present similar ancestry values. The results obtained illustrate the importance of having a good balance/compromise between not only the number of markers and their ability to differentiate ancestral populations, but also a balanced differentiation among reference groups, to obtain more precise values of genetic ancestry. This work also highlights the importance of estimating errors associated with the use of a limited number of markers. We demonstrate that although these errors have a moderate effect at the population level, they may have an important impact at the individual level. Considering that many AIM-sets are being described for inferences at the individual level and not at the population level, e.g., in association studies or the determination of a suspect's BGA, the results of this work point to the need of a more careful evaluation of the uncertainty associated with the ancestry estimates in admixed populations, when small AIM-sets are used.