Browsing by Subject "HYBRIDIZATION"

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  • Reinsalu, Olavi; Scheler, Ott; Mikelsaar, Ruth; Mikelsaar, Aavo-Valdur; Hallap, Triin; Jaakma, Ülle; Padrik, Peeter; Kavak, Ants; Salumets, Andres; Kurg, Ants (2019)
    Background: Usage of sexed semen that allows to choose the gender of the calves, is commonly practiced in livestock industry as a profitable breeding alternative, especially in dairy farming. The flow cytometric cell sorting is the only commercially available method for bovine sperm sexing. For validation of the sexing procedure several methods have been developed including sperm fluorescence in situ hybridisation techniques. Latter usually include the use of pre-labelled nucleotides for probe synthesis which is relatively expensive approach compared to combined application of aminoallyl-dUTP and chemical binding of fluorescent dyes. Here a sex determining dual colour bovine sperm fluorescence in situ hybridisation method is presented which is considered more cost-effective technique than the previously reported approaches. Results: The reliability of sex chromosome identifying probes, designed in silico, was proven on bovine metaphase plate chromosomes and through comparison with a commercially available standard method. In the dual colour FISH experiments of unsexed and sexed bovine sperm samples the hybridisation efficiency was at least 98%, whereas the determined sex ratios were not statistically different from the expected. Very few cells carried both of the sex chromosome-specific signals (less than 0.2%). Conclusions: A protocol for a dual colour bovine sperm FISH method is provided which is cost-effective, simple and fast for sex determination of spermatozoa in bull semen samples.
  • Ruotsalainen, Juho; Hujanen, Jaana; Villi, Mikko (2019)
    As pioneers of new ideas and practices, many entrepreneurial journalists spearhead the change of journalism towards hybridity. By applying appraisal theory, this article examines a hybrid of objectivity and dialogue in daily news articles by five entrepreneurial journalism outlets – Axios, MustRead, National Observer, The Skimm and the Voice of San Diego. For comparative purposes, a dataset from three legacy media outlets was also analysed. The results show that the entrepreneurial journalism outlets employ journalistic dialogue in otherwise stylistically objective news texts notably more often than do legacy media outlets. Dialogic registers provide subtle, non-partisan assessments of events and issues and make the news more informal. Such a hybrid form of journalism serves the functions of sense-making, establishing an interpersonal connection between ‘private’ audiences and ‘public’ news, and connecting journalism with fields outside of its core. By doing so, the hybrid journalism of entrepreneurial journalists offers a distinctive vision of the futures of news journalism.
  • Day-Williams, Aaron G.; McLay, Kirsten; Drury, Eleanor; Edkins, Sarah; Coffey, Alison J.; Palotie, Aarno; Zeggini, Eleftheria (2011)
  • Filppu, Pauliina; Ramanathan, Jayendrakishore Tanjore; Granberg, Kirsi J.; Gucciardo, Erika; Haapasalo, Hannu; Lehti, Kaisa; Nykter, Matti; Le Joncour, Vadim; Laakkonen, Pirjo (2021)
    Glioma stem cells (GSCs) drive propagation and therapeutic resistance of glioblastomas, the most aggressive diffuse brain tumors. However, the molecular mechanisms that maintain the stemness and promote therapy resistance remain poorly understood. Here we report CD109/STAT3 axis as crucial for the maintenance of stemness and tumorigenicity of GSCs and as a mediator of chemoresistance. Mechanistically, CD109 physically interacts with glycoprotein 130 to promote activation of the IL-6/STAT3 pathway in GSCs. Genetic depletion of CD109 abolished the stemness and self-renewal of GSCs and impaired tumorigenicity. Loss of stemness was accompanied with a phenotypic shift of GSCs to more differentiated astrocytic-like cells. Importantly, genetic or pharmacologic targeting of CD109/STAT3 axis sensitized the GSCs to chemotherapy, suggesting that targeting CD109/STAT3 axis has potential to overcome therapy resistance in glioblastoma.
  • Kallijärvi, Jukka; Stratoulias, Vassilis; Virtanen, Kristel; Hietakangas, Ville; Heino, Tapio I.; Saarma, Mart (2012)
  • Saura, Anssi; Von Schoultz, Barbara; Saura, Anja O.; Brown, JR., Keith S. (2013)
  • Feng, Xueyun; Merilä, Juha; Löytynoja, Ari (2022)
    Introgressive hybridization is an important process in evolution but challenging to identify, undermining the efforts to understand its role and significance. On the contrary, many analytical methods assume direct descent from a single common ancestor, and admixture among populations can violate their assumptions and lead to seriously biased results. A detailed analysis of 888 whole-genome sequences of nine-spined sticklebacks (Pungitius pungitius) revealed a complex pattern of population ancestry involving multiple waves of gene flow and introgression across northern Europe. The two recognized lineages were found to have drastically different histories, and their secondary contact zone was wider than anticipated, displaying a smooth gradient of foreign ancestry with some curious deviations from the expected pattern. Interestingly, the freshwater isolates provided peeks into the past and helped to understand the intermediate states of evolutionary processes. Our analyses and findings paint a detailed picture of the complex colonization history of northern Europe and provide backdrop against which introgression and its role in evolution can be investigated. However, they also expose the challenges in analyses of admixed populations and demonstrate how hidden admixture and colonization history misleads the estimation of admixture proportions and population split times.
  • Laakkonen, Hanna; Hardman, Michael; Strelkov, Petr; Väinölä, Risto (2021)
    The amphi-boreal faunal element comprises closely related species and conspecific populations with vicarious distributions in the North Atlantic and North Pacific basins. It originated from an initial trans-Arctic dispersal in the Pliocene after the first opening of the Bering Strait, and subsequent inter-oceanic vicariance through the Pleistocene when the passage through the Arctic was severed by glaciations and low sea levels. Opportunities for further trans-Arctic dispersal have risen at times, however, and molecular data now expose more complex patterns of inter-oceanic affinities and dispersal histories. For a general view on the trans-Arctic dynamics and of the roles of potential dispersal-vicariance cycles in generating systematic diversity, we produced new phylogeographic data sets for amphi-boreal taxa in 21 genera of invertebrates and vertebrates, and combined them with similar published data sets of mitochondrial coding gene variation, adding up to 89 inter-oceanic comparisons involving molluscs, crustaceans, echinoderms, polychaetes, fishes and mammals. Only 39% of the cases correspond to a simple history of Pliocene divergence; in most taxonomical groups, the range of divergence estimates implies connections through the entire Pliocene-Pleistocene-Holocene time frame. Repeated inter-oceanic exchange was inferred for 23 taxa, and the latest connection was usually post-glacial. Such repeated invasions have usually led to secondary contacts and occasionally to widespread hybridization between the different invasion waves. Late- or post-glacial exchange was inferred in 46% of the taxa, stressing the importance of the relatively recent invasions to the current diversity in the North Atlantic. Individual taxa also showed complex idiosyncratic patterns and histories, and several instances of cryptic speciation were recognized. In contrast to a simple inter-oceanic vicariance scenario underlying amphi-boreal speciation, the data expose complex patterns of reinvasion and reticulation that complicate the interpretation of taxon boundaries in the region.
  • Martin-Roy, Raphael; Nygard, Elisa; Nouhaud, Pierre; Kulmuni, Jonna (2021)
    Genetic variability is essential for adaptation and could be acquired via hybridization with a closely related lineage. We use ants to investigate thermal adaptation and the link between temperature and genetic variation arising from hybridization. We test for differences in cold and heat tolerance between Finnish Formica polyctena and Formica aquilonia wood ants and their naturally occurring hybrids. Using workers, we find that the parental individuals differ in both cold and heat tolerances and express thermal limits that reflect their global distributions. Hybrids, however, cannot combine thermal tolerance of parental species as they have the same heat tolerance as F. polyctena but not the same cold tolerance as F. aquilonia. We then focus on a single hybrid population to investigate the relationship between temperature variation and genetic variation across 16 years using reproductive individuals. On the basis of the thermal tolerance results, we expected the frequency of putative F. polyctena alleles to increase in warm years and F. aquilonia alleles to increase in cold years. We find support for this in hybrid males but not in hybrid females. These results contribute to understanding the outcomes of hybridization, which may be sex specific or depend on the environment. Furthermore, genetic variability resulting from hybridization could help hybrid wood ants cope with changing thermal conditions.
  • Benard-Slagter, Anne; Zondervan, Ilse; de Groot, Karel; Ghazavi, Farzaneh; Sarhadi, Virinder; Van Vlierberghe, Pieter; De Moerloose, Barbara; Schwab, Claire; Vettenranta, Kim; Harrison, Christine J.; Knuutila, Sakari; Schouten, Jan; Lammens, Tim; Savola, Suvi (2017)
    Recurrent and clonal genetic alterations are characteristic of different subtypes of T- and B-cell lymphoblastic leukemia (ALL), and several subtypes are strong independent predictors of clinical outcome. A next-generation sequencing based multiplex ligation-dependent probe amplification variant (digitalMLPA) has been developed enabling simultaneous detection of copy number alterations (CNAs) of up to 1000 target sequences. This novel digitalMLPA assay was designed and optimized to detect CNAs of 56 key target genes and regions in ALL. A set of digital karyotyping probes has been included for the detection of gross ploidy changes, to determine the extent of CNAs, while also serving as reference probes for data normalization. Sixty-seven ALL patient samples (including B- and T-cell ALL), previously characterized for genetic aberrations by standard MLPA, array comparative genomic hybridization, and/or single-nucleotide polymorphism array, were analyzed single blinded using digitalMLPA. The digitalMLPA assay reliably identified whole chromosome losses and gains (including high hyperdiploidy), whole gene deletions or gains, intrachromosomal amplification of chromosome 21, fusion genes, and intragenic deletions, which were confirmed by other methods. Furthermore, subclonal alterations were reliably detected if present in at least 20% to 30% of neoplastic cells. The diagnostic sensitivity of the digitaLMLPA assay was 98.9%, and the specificity was 97.8%. These results merit further consideration of digitalMLPA as a valuable alternative for genetic work-up of newly diagnosed ALL patients.
  • Metso, Leena; Maki, Minna; Tissari, Paivi; Remes, Ville; Piiparinen, Pasi; Kirveskari, Juha; Tarkka, Eveliina; Anttila, Veli-Jukka; Vaara, Martti; Huotari, Kaisa (2014)
  • Priklopil, Tadeas; Kisdi, Eva; Gyllenberg, Mats (2015)
    We consider mating strategies for females who search for males sequentially during a season of limited length. We show that the best strategy rejects a given male type if encountered before a time-threshold but accepts him after. For frequency-independent benefits, we obtain the optimal time-thresholds explicitly for both discrete and continuous distributions of males, and allow for mistakes being made in assessing the correct male type. When the benefits are indirect (genes for the offspring) and the population is under frequency-dependent ecological selection, the benefits depend on the mating strategy of other females as well. This case is particularly relevant to speciation models that seek to explore the stability of reproductive isolation by assortative mating under frequency-dependent ecological selection. We show that the indirect benefits are to be quantified by the reproductive values of couples, and describe how the evolutionarily stable time-thresholds can be found. We conclude with an example based on the Levene model, in which we analyze the evolutionarily stable assortative mating strategies and the strength of reproductive isolation provided by them.
  • Junnila, Siina; Kokkola, Arto; Karjalainen-Lindsberg, Marja; Puolakkainen, Pauli; Monni, Outi (2010)
  • Pulido-Santacruz, Paola; Aleixo, Alexandre; Weir, Jason T. (2020)
    The incidence of introgression during the diversification process and the timespan following divergence when introgression is possible are poorly understood in the neotropics where high species richness could provide extensive opportunities for genetic exchange. We used thousands of genome-wide SNPs to infer phylogenetic relationships, calculate ages of splitting, and to estimate the timing of introgression in a widespread avian neotropical genus of woodcreepers. Five distinct introgression events were reconstructed involving taxa classified both as subspecies and species including lineages descending from the basal-most split, dated to 7.3 million years ago. Introgression occurred between just a few hundred thousand to about 2.5 million years following divergence, suggesting substantial portions of the genome are capable of introgressing across taxa boundaries during a protracted time window of a few million years following divergence. Despite this protracted time window, we found that the proportion of the genome introgressing (6-11%) declines with the time of introgression following divergence, suggesting that the genome becomes progressively more immune to introgression as reproductive isolation increases.
  • Habermann, Jens K.; Buendgen, Nana K.; Gemoll, Timo; Hautaniemi, Sampsa; Lundgren, Caroline; Wangsa, Danny; Doering, Jana; Bruch, Hans-Peter; Nordstroem, Britta; Roblick, Uwe J.; Jornvall, Hans; Auer, Gert; Ried, Thomas (2011)
  • Crowgey, Erin L.; Soini, Tea; Shah, Nidhi; Pauniaho, Satu-Liisa; Lahdenne, Pekka; Wilson, David B.; Heikinheimo, Markku; Druley, Todd E. (2020)
    Purpose: Pediatric germ cell tumors are rare, representing about 3% of childhood malignancies in children less than 15 years of age, presenting in neonates or adolescents with a greater incidence noted in older adolescents. Aberrations in primordial germ cell proliferation/differentiation can lead to a variety of neoplasms, including teratomas, embryonal carcinoma, choriocarcinoma, and yolk sac tumors. Patients and Methods: Three Finnish families with varying familial germ cell tumors were identified, and whole-genome sequencing was performed using an Illumina sequencing platform. In total, 22 unique subjects across the three families were sequenced. Family 1 proband (female) was affected by malignant ovarian teratoma, Family 2 proband (female) was affected by sacrococcygeal teratoma with yolk sac tumor in the setting of Cornelia de Lange syndrome, and Family 3 proband (male) was affected by malignant testicular teratoma. Rare variants were identified using an autosomal recessive or de novo model of inheritance. Results: For family 1 proband (female), an autosomal recessive or de novo model of inheritance identified variants of interest in the following genes: CD109, IKBKB, and CTNNA3, SUPT6H, MUC5AC, and FRG1. Family 2 proband (female) analysis identified gene variants of interest in the following genes: LONRF2, ANO7, HS6ST1, PRB2, and DNM2. Family 3 proband (male) analysis identified the following potential genes: CRIPAK, KRTAP5-7, and CACNA1B. Conclusion: Leveraging deep pedigrees and next-generation sequencing, rare germline variants were identified that were enriched in three families from Finland with a history of familial germ cell tumors. The data presented support the importance of germline mutations when analyzing complex cancers with a low somatic mutation landscape.
  • Jamshidi, Maral; Fagerholm, Rainer; Muranen, Taru A.; Kaur, Sippy; Potdar, Swapnil; Khan, Sofia; Netti, Eliisa; Mpindi, John-Patrick; Yadav, Bhagwan; Kiiski, Johanna I.; Aittomäki, Kristiina; Heikkilä, Päivi; Saarela, Jani; Bützow, Ralf; Blomqvist, Carl; Nevanlinna, Heli (2021)
  • Mahlamaki, E H; Kauraniemi, P; Monni, O; Wolf, Maija; Hautaniemi, S; Kallioniemi, Anne (2004)
  • Lan, Tianying; Leppälä, Kalle; Tomlin, Crystal; Talbot, Sandra L.; Sage, George K.; Farley, Sean D.; Shideler, Richard T.; Bachmann, Lutz; Wiig, Øystein; Albert, Victor A.; Salojärvi, Jarkko; Mailund, Thomas; Drautz-Moses, Daniela I.; Schuster, Stephan C.; Herrera-Estrella, Luis; Lindqvist, Charlotte (2022)
    The polar bear (Ursus maritimus) has become a symbol of the threat to biodiversity from climate change. Understanding polar bear evolutionary history may provide insights into apex carnivore responses and prospects during periods of extreme environmental perturbations. In recent years, genomic studies have examined bear speciation and population history, including evidence for ancient admixture between polar bears and brown bears (Ursus arctos). Here, we extend our earlier studies of a 130,000- to 115,000-y-old polar bear from the Svalbard Archipelago using a 10x coverage genome sequence and 10 new genomes of polar and brown bears from contemporary zones of overlap in northern Alaska. We demonstrate a dramatic decline in effective population size for this ancient polar bear's lineage, followed by a modest increase just before its demise. A slightly higher genetic diversity in the ancient polar bear suggests a severe genetic erosion over a prolonged bottleneck in modern polar bears. Statistical fitting of data to alternative admixture graph scenarios favors at least one ancient introgression event from brown bears into the ancestor of polar bears, possibly dating back over 150,000 y. Gene flow was likely bidirectional, but allelic transfer from brown into polar bear is the strongest detected signal, which contrasts with other published work. These findings may have implications for our understanding of climate change impacts: Polar bears, a specialist Arctic lineage, may not only have undergone severe genetic bottlenecks but also been the recipient of generalist, boreal genetic variants from brown bears during critical phases of Northern Hemisphere glacial oscillations.
  • Zhou, Wenjing; Jirstrom, Karin; Johansson, Christine; Amini, Rose-Marie; Blomqvist, Carl; Agbaje, Olorunsola; Warnberg, Fredrik (2010)
    Background: Microarray gene-profiling of invasive breast cancer has identified different subtypes including luminal A, luminal B, HER2-overexpressing and basal-like groups. Basal-like invasive breast cancer is associated with a worse prognosis. However, the prognosis of basal-like ductal carcinoma in situ (DCIS) is still unknown. Our aim was to study the prognosis of basal-like DCIS in a large population-based cohort. Methods: All 458 women with a primary DCIS diagnosed between 1986 and 2004, in Uppland and Vastmanland, Sweden were included. TMA blocks were constructed. To classify the DCIS tumors, we used immunohistochemical (IHC) markers (estrogen-, progesterone-, HER2, cytokeratin 5/6 and epidermal growth factor receptor) as a surrogate for the gene expression profiling. The association with prognosis was examined for basal-like DCIS and other subtypes using Kaplan-Meier survival analyses and Cox proportional hazards regression models. Results: IHC data were complete for 392 women. Thirty-two were basal-like (8.2%), 351 were luminal or HER2-positive (89.5%) and 9 unclassified (2.3%). Seventy-six women had a local recurrence of which 34 were invasive. Another 3 women had general metastases as first event. Basal-like DCIS showed a higher risk of local recurrence and invasive recurrence 1.8 (Confidence interval (CI) 95%, 0.8-4.2) and 1.9 (0.7-5.1), respectively. However, the difference was not statistically significant. Also, no statistically significant increased risk was seen for triple-negative or high grade DCIS. Conclusions: Basal-like DCIS showed about a doubled, however not statistically significant risk for local recurrence and developing invasive cancer compared with the other molecular subtypes. Molecular subtyping was a better prognostic parameter than histopathological grade.