A previous autosomal STR study provided evidence of a connection between the ancient Soliga tribe at the southern tip of the Indian subcontinent and Australian aboriginal populations, possibly reflecting an eastbound coastal migration circa (15 Kya). The Soliga are considered to be among India's earliest inhabitants. In this investigation, we focus on the Y chromosomal characteristics shared between the Soliga population and other Indian tribes as well as western Eurasia and Sub-Saharan Africa groups.
View Article and Find Full Text PDFVascular anomalies, including local and peripheral thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of deregulation of the cancer cell genome and epigenome. Although the molecular effectors of these changes are poorly understood, the upregulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk for venous thromboembolism (VTE) in GBM patients. Therefore, regulation of this platelet-activating protein by transforming events in cancer cells is of considerable interest.
View Article and Find Full Text PDFA previous autosomal STR study provided evidence of a connection between the ancient Soliga tribe at the southern tip of the Indian subcontinent and Australian aboriginal populations, possibly reflecting an eastbound coastal migration circa (15 Kya). The Soliga are considered to be among India's earliest inhabitants. In this investigation, we focus on the Y chromosomal characteristics shared between the Soliga population and other Indian tribes as well as western Eurasia and Sub-Saharan Africa groups.
View Article and Find Full Text PDFOncogenic transformation impacts cancer cell interactions with their stroma, including through formation of abnormal blood vessels. This influence is often attributed to angiogenic growth factors, either soluble, or associated with tumor cell-derived extracellular vesicles (EVs). Here we examine some of the cancer-specific components of EV-mediated tumor-vascular interactions, including the impact of genetic driver mutations and genetic instability.
View Article and Find Full Text PDFDetection of unique oncogenic alterations encoded by the sequence or biochemical modification in cancer-associated transforming macromolecules has revolutionized diagnosis, classification and management of human cancers. While these signatures were traditionally regarded as largely intracellular and confined to the tumor mass, oncogenic mutations and actionable cancer-related molecular alterations can also be accessed remotely through their recovery from biofluids of either rare circulating tumor cells (CTCs), or of more abundant non-cellular carriers, such as extracellular vesicles (EVs), protein complexes, or cell-free tumor DNA (ctDNA). Tumor-related macromolecules may also accumulate in circulating platelets.
View Article and Find Full Text PDFMolecular profiling of human cancers revealed a startling diversity in disease-causing mechanisms superseding histological and anatomical commonalities. The emerging molecular subtypes and disease entities are often driven by distinct oncogenic pathways and their effectors, including those acting extracellularly on the vascular and coagulation systems. Indeed, several oncogenic mutations such as those affecting protein-coding genes (RAS, EGFR, PTEN, TP53) and non-coding RNA (microRNA) regulate multiple effectors of the coagulation system (coagulome), including tissue factor, protease activated receptors, clotting factors, mediators of platelet function and fibrinolysis.
View Article and Find Full Text PDFPathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids.
View Article and Find Full Text PDFA total of 223 samples from the general population of Ladakh in Northwestern India were amplified at 17 Y-STR loci using the AmpFlSTR® Yfiler™ system. The DNA profiles generated were employed to generate allelic frequencies, gene diversity, haplotype diversity and discrimination capacity values as well as number of different haplotypes, fraction of unique haplotypes and Rst pair wise genetic distances. Multidimensional Scaling (MDS) and Correspondence Analysis (CA) were performed with the Rst values and allelic frequencies, respectively.
View Article and Find Full Text PDFExtracellular vesicles (EVs) enable the exit of regulatory, mutant and oncogenic macromolecules (proteins, RNA and DNA) from their parental tumor cells and uptake of this material by unrelated cellular populations. Among the resulting biological effects of interest is the notion that cancer-derived EVs may mediate horizontal transformation of normal cells through transfer of mutant genes, including mutant ras. Here, we report that H-ras-mediated transformation of intestinal epithelial cells (IEC-18) results in the emission of exosome-like EVs containing genomic DNA, HRAS oncoprotein and transcript.
View Article and Find Full Text PDFBrain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs).
View Article and Find Full Text PDFAt an average altitude of 4000m above sea level, the Tibetan plateau is one of the highest plains on the planet. It is surrounded on three sides by massive mountain ranges: the Kunlun, the Karakoram and the Himalayas. These natural barriers have kept Tibet relatively isolated.
View Article and Find Full Text PDFExtracellular vesicles (EVs), including exosomes, are a subject of intense interest due to their emission by cancer cells and role in intercellular communication. Earlier reports suggested that oncogenes, such as RAS, MET or EGFR, drive cellular vesiculation. Interestingly, these oncogenes may also traffic between cells using the EV-mediated emission and uptake processes.
View Article and Find Full Text PDFOwing to its geographic location near the longitudinal center of Asia, Ladakh, the land of high passes, has witnessed numerous demographic movements during the past millenniums of occupation. In an effort to view Ladakh's multicultural history from a paternal genetic perspective, we performed a high-resolution Y-chromosomal survey of Ladakh, within the context of Y haplogroup and haplotype distributions of 41 Asian reference populations. The results of this investigation highlight the rich ethnic and genetic diversity of Ladkah which includes genetic contributions from disparate regions of the continent including, West, East, South and Central Asia.
View Article and Find Full Text PDFHere, we present 12 loci paternal haplotypes (Y-STR profiles) against the backdrop of the Y-SNP marker system of Bantu males from the Maputo Province of Southeast Africa, a region believed to represent the southeastern fringe of the Bantu expansion. Our Maputo Bantu group was analyzed within the context of 27 geographically relevant reference populations in order to ascertain its genetic relationship to other Bantu and non Bantu (Pygmy, Khoisan and Nilotic) sub-equatorial tribes from West and East Africa. This study entails statistical pair wise comparisons and multidimensional scaling based on YSTR Rst distances, network analyses of Bantu (B2a-M150) and Pygmy (B2b-M112) lineages as well as an assessment of Y-SNP distribution patterns.
View Article and Find Full Text PDFCell free DNA is often regarded as a source of genetic cancer biomarkers, but the related mechanisms of DNA release, composition and biological activity remain unclear. Here we show that rat epithelial cell transformation by the human H-ras oncogene leads to an increase in production of small, exosomal-like extracellular vesicles by viable cancer cells. These EVs contain chromatin-associated double-stranded DNA fragments covering the entire host genome, including full-length H-ras.
View Article and Find Full Text PDFPrevious studies have shown that India's vast coastal rim played an important role in the dispersal of modern humans out of Africa but the Karnataka state, which is located on the southwest coast of India, remains poorly characterized genetically. In the present study, two Dravidian populations, namely Lingayat (N=101) and Vokkaliga (N=102), who represent the two major communities of the Karnataka state, were examined using high-resolution analyses of Y-chromosome single nucleotide polymorphisms (Y-SNPs) and seventeen short tandem repeat (Y-STR) loci. Our results revealed that the majority of the Lingayat and Vokkaliga paternal gene pools are composed of four Y-chromosomal haplogroups (H, L, F* and R2) that are frequent in the Indian subcontinent.
View Article and Find Full Text PDFThe Himalayan mountain range is strategically located at the crossroads of the major cultural centers in Asia, the Middle East and Europe. Although previous Y-chromosome studies indicate that the Himalayas served as a natural barrier for gene flow from the south to the Tibetan plateau, this region is believed to have played an important role as a corridor for human migrations between East and West Eurasia along the ancient Silk Road. To evaluate the effects of the Himalayan mountain range in shaping the maternal lineages of populations residing on either side of the cordillera, we analyzed mitochondrial DNA variation in 344 samples from three Nepalese collections (Newar, Kathmandu and Tamang) and a general population of Tibet.
View Article and Find Full Text PDFIn the present study, 17 Y-chromosomal STR (Y-STR) loci were typed in 218 unrelated males from Sousse, Central-East Tunisia, to evaluate forensic and population genetic applications of the data. A total of 154 different haplotypes were identified, 127 (82.5%) of which were unique, with the most frequent haplotype occurring in 14 individuals (6.
View Article and Find Full Text PDFOne of the primary unanswered questions regarding the dispersal of Romani populations concerns the geographical region and/or the Indian caste/tribe that gave rise to the proto-Romani group. To shed light on this matter, 161 Y-chromosomes from Roma, residing in two different provinces of Serbia, were analyzed. Our results indicate that the paternal gene pool of both groups is shaped by several strata, the most prominent of which, H1-M52, comprises almost half of each collection's patrilineages.
View Article and Find Full Text PDFCentral Asia has served as a corridor for human migrations providing trading routes since ancient times. It has functioned as a conduit connecting Europe and the Middle East with South Asia and far Eastern civilizations. Therefore, the study of populations in this region is essential for a comprehensive understanding of early human dispersal on the Eurasian continent.
View Article and Find Full Text PDFIn the present study, we analyzed 17 Y-STR loci in 350 Tibetan males from three culturally defined regions of historical Tibet: Amdo (88), Kham (109) and U-Tsang (153). A total of 299 haplotypes were observed, 272 (90.9%) of which were unique.
View Article and Find Full Text PDFPrevious studies have revealed that the European Roma share close genetic, linguistic and cultural similarities with Indian populations despite their disparate geographical locations and divergent demographic histories. In this study, we report for the first time Y-chromosome distributions in three Roma collections residing in Belgrade, Vojvodina and Kosovo. Eighty-eight Y-chromosomes were typed for 14 SNPs and 17 STRs.
View Article and Find Full Text PDFLinguistic and ethnic diversity throughout the Himalayas suggests that this mountain range played an important role in shaping the genetic landscapes of the region. Previous Y-chromosome work revealed that the Himalayas acted as a biased bidirectional barrier to gene flow across the cordillera. In the present study, 17 Y-chromosomal short tandem repeat (Y-STR) loci included in the AmpFlSTR® Yfiler kit were analyzed in 344 unrelated males from three Nepalese populations (Tamang, Newar, and Kathmandu) and a general collection from Tibet.
View Article and Find Full Text PDFThe Himalayan mountain range has played a dual role in shaping the genetic landscape of the region by (1) delineating east-west migrations including the Silk Road and (2) restricting human dispersals, especially from the Indian subcontinent into the Tibetan plateau. In this study, 15 hypervariable autosomal STR loci were employed to evaluate the genetic relationships of three populations from Nepal (Kathmandu, Newar and Tamang) and a general collection from Tibet. These Himalayan groups were compared to geographically targeted worldwide populations as well as Tibeto-Burman (TB) speaking groups from Northeast India.
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