Browsing by Subject "GENERATION"

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  • Batsyts, Sviatoslav; Vedmid, Roman; Namyslo, Jan C.; Nieger, Martin; Schmidt, Andreas (2019)
    1-Methylquinolinium salts substituted at the C3 position with phenyl, naphthalen-1-yl, phenanthren-9-yl, and pentaphenyl phenyl as well as aryl ethynyl substituents were prepared. The phenyl, naphthalen-1-yl, and phenanthren-9-yl substituents are in conjugation with the quinolinium ring, and the sterically crowded pentaphenyl phenyl residue causes a propeller-type molecule possessing a calculated dihedral angle between aryl substituent and the quinolinium ring of approximately 54 degrees. The different influences of the substituents including the aryl ethynyl residues on the pi-architecture is well reflected in their frontier orbital profiles, their spectroscopic properties, and in their ability to form N-heterocyclic carbenes. The latter were generated from the C3-aryl substituted quinolinium salts and trapped as sulfur and selenium adducts, whereas the aryl ethynyl substituted derivatives failed to undergo the NHC generation under the conditions applied. Se-77 NMR measurements of the corresponding selenones reveal that quinolin-2-ylidenes are electron poor carbenes with strong pi-acceptor character.
  • Van Horebeek, Lies; Hilven, Kelly; Mallants, Klara; Van Nieuwenhuijze, Annemarie; Kelkka, Tiina; Savola, Paula; Mustjoki, Satu; Schlenner, Susan M.; Liston, Adrian; Dubois, Benedicte; Goris, An (2019)
    The role of somatic variants in diseases beyond cancer is increasingly being recognized, with potential roles in autoinflammatory and autoimmune diseases. However, as mutation rates and allele fractions are lower, studies in these diseases are substantially less tolerant of false positives, and bio-informatics algorithms require high replication rates. We developed a pipeline combining two variant callers, MuTect2 and VarScan2, with technical filtering and prioritization. Our pipeline detects somatic variants with allele fractions as low as 0.5% and achieves a replication rate of > 55%. Validation in an independent data set demonstrates excellent performance (sensitivity > 57%, specificity > 98%, replication rate > 80%). We applied this pipeline to the autoimmune disease multiple sclerosis (MS) as a proof-of-principle. We demonstrate that 60% of MS patients carry 2-10 exonic somatic variants in their peripheral blood T and B cells, with the vast majority (80%) occurring in T cells and variants persisting over time. Synonymous variants significantly co-occur with non-synonymous variants. Systematic characterization indicates somatic variants are enriched for being novel or very rare in public databases of germline variants and trend towards being more damaging and conserved, as reflected by higher phred-scaled combined annotation-dependent depletion (CADD) and genomic evolutionary rate profiling (GERP) scores. Our pipeline and proof-of-principle now warrant further investigation of common somatic genetic variation on top of inherited genetic variation in the context of autoimmune disease, where it may offer subtle survival advantages to immune cells and contribute to the capacity of these cells to participate in the autoimmune reaction.
  • Iso-Touru, Terhi; Wurmser, Christine; Venhoranta, Heli; Hiltpold, Maya; Savolainen, Tujia; Sironen, Anu; Fischer, Konrad; Flisikowski, Krzysztof; Fries, Ruedi; Vicente-Carrillo, Alejandro; Alvarez-Rodriguez, Manuel; Nagy, Szabolcs; Mutikainen, Mervi; Peippo, Jaana; Taponen, Juhani; Sahana, Goutam; Guldbrandtsen, Bernt; Simonen, Henri; Rodriguez-Martinez, Heriberto; Andersson, Magnus; Pausch, Hubert (2019)
    Background: Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected. Results: Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P=0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5 splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle. Conclusions; Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).
  • Purhonen, Janne; Grigorjev, Vladislav; Ekiert, Robert; Aho, Noora; Rajendran, Jayasimman; Pietras, Rafal; Truve, Katarina; Wikström, Mårten; Sharma, Vivek; Osyczka, Artur; Fellman, Vineta; Kallijärvi, Jukka (2020)
    We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1/(p.S78G) mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cyb(p.D254N)), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1/(p.S78G) tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc(1) complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes.
  • Saarimaki-Vire, Jonna; Balboa, Diego; Russell, Mark A.; Saarikettu, Juha; Kinnunen, Matias; Keskitalo, Salla; Malhi, Amrinder; Valensisi, Cristina; Andrus, Colin; Eurola, Solja; Grym, Heli; Ustinov, Jarkko; Wartiovaara, Kirmo; Hawkins, R. David; Silvennoinen, Olli; Varjosalo, Markku; Morgan, Noel G.; Otonkoski, Timo (2017)
    Activating germline mutations in STAT3 were recently identified as a cause of neonatal diabetes mellitus associated with beta-cell autoimmunity. We have investigated the effect of an activating mutation, STAT3(K392R,) on pancreatic development using induced pluripotent stem cells (iPSCs) derived from a patient with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm differentiated similarly from STAT3(K392R) and healthy-control cells, but in later stages, NEUROG3 expressionwas upregulated prematurely in STAT3(K392R) cells together with insulin (INS) and glucagon (GCG). RNA sequencing (RNA-seq) showed robust NEUROG3 downstream targets upregulation. STAT3 mutation correction with CRISPR/Cas9 reversed completely the disease phenotype. STAT3(K392R) -activating properties were not explained fully by altered DNA-binding affinity or increased phosphorylation. Instead, reporter assays demonstrated NEUROG3 promoter activation by STAT3 in pancreatic cells. Furthermore, proteomic and immunocytochemical analyses revealed increased nuclear translocation of STAT3(K392R). Collectively, our results demonstrate that the STAT3(K392R) mutation causes premature endocrine differentiation through direct induction of NEUROG3 expression.
  • Wang, Xin; Ye, Lingling; Lyu, Munan; Ursache, Robertas; Löytynoja, Ari; Mähönen, Ari Pekka (2020)
    Conditional manipulation of gene expression is a key approach to investigating the primary function of a gene in a biological process. While conditional and cell-type-specific overexpression systems exist for plants, there are currently no systems available to disable a gene completely and conditionally. Here, we present a new tool with which target genes can efficiently and conditionally be knocked out by genome editing at any developmental stage. Target genes can also be knocked out in a cell-type-specific manner. Our tool is easy to construct and will be particularly useful for studying genes having null alleles that are non-viable or show pleiotropic developmental defects.
  • Mahil, Satveer K.; Twelves, Sophie; Farkas, Katalin; Setta-Kaffetzi, Niovi; Burden, A. David; Gach, Joanna E.; Irvine, Alan D.; Kepiro, Laszlo; Mockenhaupt, Maja; Oon, Hazel H.; Pinner, Jason; Ranki, Annamari; Seyger, Marieke M. B.; Soler-Palacin, Pere; Storan, Eoin R.; Tan, Eugene S.; Valeyrie-Allanore, Laurence; Young, Helen S.; Trembath, Richard C.; Choon, Siew-Eng; Szell, Marta; Bata-Csorgo, Zsuzsanna; Smith, Catherine H.; Di Meglio, Paola; Barker, Jonathan N.; Capon, Francesca (2016)
    Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-kappa B activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36 alpha, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.
  • Szibor, Annett; Lehtimäki, Jarmo; Ylikoski, Jukka; Aarnisalo, Antti A.; Mäkitie, Antti; Hyvärinen, Petteri (2018)
    Affective processing appears to be altered in tinnitus, and the condition is to a large extent characterized by the emotional reaction to the phantom sound. Psychophysiological models of tinnitus and supporting brain imaging studies have suggested a role for the limbic system in the emergence and maintenance of tinnitus. It is not clear whether the tinnitus-related changes in these systems are specific for tinnitus only, or whether they affect emotional processing more generally. In this study, we aimed to quantify possible deviations in affective processing in tinnitus patients by behavioral and physiological measures. Tinnitus patients rated the valence and arousal of sounds from the International Affective Digitized Sounds database. Sounds were chosen based on the normative valence ratings, that is, negative, neutral, or positive. The individual autonomic response was measured simultaneously with pupillometry. We found that the subjective ratings of the sounds by tinnitus patients differed significantly from the normative ratings. The difference was most pronounced for positive sounds, where sounds were rated lower on both valence and arousal scales. Negative and neutral sounds were rated differently only for arousal. Pupil measurements paralleled the behavioral results, showing a dampened response to positive sounds. Taken together, our findings suggest that affective processing is altered in tinnitus patients. The results are in line with earlier studies in depressed patients, which have provided evidence in favor of the so-called positive attenuation hypothesis of depression. Thus, the current results highlight the close link between tinnitus and depression.
  • Nurminen, Kimmo; Litkey, Paula; Honkavaara, Eija; Vastaranta, Mikko; Holopainen, Markus; Lyytikäinen-Saarenmaa, Päivi; Kantola, Tuula; Lyytikäinen, Minna (2015)
    Photogrammetric aerial film image archives are scanned into digital form in many countries. These data sets offer an interesting source of information for scientists from different disciplines. The objective of this investigation was to contribute to the automation of a generation of 3D environmental model time series when using small-scale airborne image archives, especially in forested scenes. Furthermore, we investigated the usability of dense digital surface models (DSMs) generated using these data sets as well as the uncertainty propagation of the DSMs. A key element in the automation is georeferencing. It is obvious that for images captured years apart, it is essential to find ground reference locations that have changed as little as possible. We studied a 68-year-long aerial image time series in a Finnish Karelian forestland. The quality of candidate ground locations was evaluated by comparing digital DSMs created from the images to an airborne laser scanning (ALS)-originated reference DSM. The quality statistics of DSMs were consistent with the expectations; the estimated median root mean squared error for height varied between 0.3 and 2 m, indicating a photogrammetric modelling error of 0.1 parts per thousand with respect to flying height for data sets collected since the 1980s, and 0.2 parts per thousand for older data sets. The results show that of the studied land cover classes, "peatland without trees" changed the least over time and is one of the most promising candidates to serve as a location for automatic ground control measurement. Our results also highlight some potential challenges in the process as well as possible solutions. Our results indicate that using modern photogrammetric techniques, it is possible to reconstruct 3D environmental model time series using photogrammetric image archives in a highly automated way.
  • Raykhel, Irina; Moafi, Fazeh; Myllymaki, Satu M.; Greciano, Patricia G.; Matlin, Karl S.; Moyano, Jose V.; Manninen, Aki; Myllyharju, Johanna (2018)
    Hypoxia and loss of cell polarity are common features of malignant carcinomas. Hypoxia-inducible factor 1 (HIF1) is the major regulator of cellular hypoxia response and mediates the activation of similar to 300 genes. Increased HIF1 signaling is known to be associated with epithelial-mesenchymal transformation. Here, we report that hypoxia disrupts polarized epithelial morphogenesis of MDCK cells in a HIF1 alpha-dependent manner by modulating the transforming growth factor-beta (TGF beta) signaling pathway. Analysis of potential HIF1 targets in the TGF beta pathway identified the bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), a transmembrane glycoprotein related to the type I receptors of the TGF beta family, whose expression was essentially lost in HIF1-depleted cells. Similar to what was observed in HIF1-deficient cells, BAMBI-depleted cells failed to efficiently activate TGF beta signaling and retained epithelial polarity during hypoxia. Taken together, we show that hypoxic conditions promote TGF beta signaling in a HIF1-dependent manner and BAMBI is identified in this pathway as a novel HIF1-regulated gene that contributes to hypoxia-induced loss of epithelial polarity.
  • Granholm, Camilla (2016)
    This article presents a qualitative study of ICT use among Finnish young people attending training programmes for youth outside employment and education. The data come from six focus group interviews and three individual interviews, as well as a single focus group interview with involved supervisors. The data was analyzed using McQuail's (1983) theory regarding the motives for individual media use. The results show that the young people use ICT primarily for entertainment, but their use is diverse. Young people choose the tools and dimensions for interaction that best fulfill their needs, blending together ingredients from both online and offline sources. Unlike previous research, young people in this study stated that they prefer talking to someone face-to-face about severe (health-related or emotional) problems. If social and youth services want to meet young people on their own terms, both online and offline services are needed.
  • Savriama, Yoland; Valtonen, Mia; Kammonen, Juhana I.; Rastas, Pasi; Smolander, Olli-Pekka; Lyyski, Annina; Häkkinen, Teemu J.; Corfe, Ian J.; Gerber, Sylvain; Salazar-Ciudad, Isaac; Paulin, Lars; Holm, Liisa; Löytynoja, Ari; Auvinen, Petri; Jernvall, Jukka (2018)
    An increasing number of mammalian species have been shown to have a history of hybridization and introgression based on genetic analyses. Only relatively few fossils, however, preserve genetic material, and morphology must be used to identify the species and determine whether morphologically intermediate fossils could represent hybrids. Because dental and cranial fossils are typically the key body parts studied in mammalian palaeontology, here we bracket the potential for phenotypically extreme hybridizations by examining uniquely preserved cranio-dental material of a captive hybrid between grey and ringed seals. We analysed how distinct these species are genetically and morphologically, how easy it is to identify the hybrids using morphology and whether comparable hybridizations happen in the wild. We show that the genetic distance between these species is more than twice the modern human–Neanderthal distance, but still within that of morphologically similar species pairs known to hybridize. By contrast, morphological and developmental analyses show grey and ringed seals to be highly disparate, and that the hybrid is a predictable intermediate. Genetic analyses of the parent populations reveal introgression in the wild, suggesting that grey–ringed seal hybridization is not limited to captivity. Taken together, we postulate that there is considerable potential for mammalian hybridization between phenotypically disparate taxa.
  • Alviano, Mario; Dodaro, Carmine; Järvisalo, Matti; Maratea, Marco; Previti, Alessandro (2018)
    Answer Set Programming (ASP) is a logic-based knowledge representation framework, supporting-among other reasoning modes-the central task of query answering. In the propositional case, query answering amounts to computing cautious consequences of the input program among the atoms in a given set of candidates, where a cautious consequence is an atom belonging to all stable models. Currently, the most efficient algorithms either iteratively verify the existence of a stable model of the input program extended with the complement of one candidate, where the candidate is heuristically selected, or introduce a clause enforcing the falsity of at least one candidate, so that the solver is free to choose which candidate to falsify at any time during the computation of a stable model. This paper introduces new algorithms for the computation of cautious consequences, with the aim of driving the solver to search for stable models discarding more candidates. Specifically, one of such algorithms enforces minimality on the set of true candidates, where different notions of minimality can be used, and another takes advantage of unsatisfiable cores computation. The algorithms are implemented in WASP, and experiments on benchmarks from the latest ASP competitions show that the new algorithms perform better than the state of the art.
  • Cai, Runlong; Attoui, Michel; Jiang, Jingkun; Korhonen, Frans; Hao, Jiming; Petäjä, Tuukka; Kangasluoma, Juha (2018)
    Classifying sub-3 nm particles effectively with relatively high penetration efficiencies and sizing resolutions is important for atmospheric new particle formation studies. A high-resolution supercritical differential mobility analyzer (half-mini DMA) was recently improved to classify aerosols at a sheath flow rate less than 100 L/min. In this study, we characterized the transfer functions, the penetration efficiencies, and the sizing resolution of the new half-mini DMA at the aerosol flow rate of 2.5-10 L/min and the sheath flow rate of 25-250 L/min using tetra-alkyl ammonium ions and tungsten oxide particles. The transfer functions of the new half-mini DMA at an aerosol flow rate lower than 5 L/min and a sheath flow rate lower than 150 L/min agree well with predictions using a theoretical diffusing transfer function. The penetration efficiencies can be approximated using an empirical formula. When classifying 1.48 nm molecular ions at an aerosol-to-sheath flow ratio of 5/50 L/min, the penetration efficiency, the sizing resolution, and the multiplicative broadening factor of the new half-mini DMA are 0.18, 6.8, and 1.11, respectively. Compared to other sub-3 nm DMAs applied in atmospheric measurements (e.g. the mini-cyDMA, the TSI DMA 3086, the TSI nanoDMA 3085, and the Grimm S-DMA), the new half-mini DMA characterized in this study is able to classify particles at higher aerosol and sheath flow rates, leading to a higher sizing resolution at the same aerosol-to-sheath flow ratio. Accordingly, the new half-mini DMA can reduce the uncertainties in atmospheric new particle formation measurement if coupled with an aerosol detector that could work at the corresponding high aerosol flow rate. (c) 2018 American Association for Aerosol Research
  • Lund, Carina; Yellapragada, Venkatram; Vuoristo, Sanna; Balboa, Diego; Trova, Sara; Allet, Cecile; Eskici, Nazli; Pulli, Kristiina; Giacobini, Paolo; Tuuri, Timo; Raivio, Taneli (2020)
    Gonadotropin-releasing hormone (GnRH) neurons provide a fundamental signal for the onset of puberty and subsequent reproductive functions by secretion of gonadotropin-releasing hormone. Their disrupted development or function leads to congenital hypogonadotropic hypogonadism (CHH). To model the development of human GnRH neurons, we generated a stable GNRH1-TdTomato reporter cell line in human pluripotent stem cells (hPSCs) using CRISPR-Cas9 genome editing. RNA-sequencing of the reporter clone, differentiated into GnRH neurons by dual SMAD inhibition and FGF8 treatment, revealed 6461 differentially expressed genes between progenitors and GnRH neurons. Expression of the transcription factor ISL1, one of the top 50 most upregulated genes in the TdTomato-expressing GnRH neurons, was confirmed in 10.5 gestational week-old human fetal GnRH neurons. Among the differentially expressed genes, we detected 15 genes that are implicated in CHH and several genes that are implicated in human puberty timing. Finally, FGF8 treatment in the neuronal progenitor pool led to upregulation of 37 genes expressed both in progenitors and in TdTomato-expressing GnRH neurons, which suggests upstream regulation of these genes by FGF8 signaling during GnRH neuron differentiation. These results illustrate how hPSC-derived human GnRH neuron transcriptomic analysis can be utilized to dissect signaling pathways and gene regulatory networks involved in human GnRH neuron development.This article has an associated First Person interview with the first author of the paper.
  • Kainulainen, Kimmo; Leskinen, Juuso; Nurmi, Sami; Takahashi, Tomo (2017)
    We investigate the CMB mu distortion in models where two uncorrelated sources contribute to primordial perturbations. We parameterise each source by an amplitude, tilt, running and running of the running. We perform a detailed analysis of the distribution signal as function of the model parameters, highlighting the differences compared to single-source models. As a specific example, we also investigate the mixed inflaton-curvaton scenario. We find that the mu distortion could efficiently break degeneracies of curvaton parameters especially when combined with future sensitivity of probing the tensor-to-scalar ratio r. For example, assuming bounds mu <0.5 x 10(-8) and r <0.01, the curvaton contribution should either vanish or the curvaton should dominate primordial perturbations and its slow-roll parameter eta(chi) is constrained to the interval -0.007 <eta(chi) <0.045.
  • Riesgo, Ana; Andrade, Sonia C. S.; Sharma, Prashant P.; Novo, Marta; Perez-Porro, Alicia R.; Vahtera, Varpu; Gonzalez, Vanessa L.; Kawauchi, Gisele Y.; Giribet, Gonzalo (2012)
    Traditionally, genomic or transcriptomic data have been restricted to a few model or emerging model organisms, and to a handful of species of medical and/or environmental importance. Next-generation sequencing techniques have the capability of yielding massive amounts of gene sequence data for virtually any species at a modest cost. Here we provide a comparative analysis of de novo assembled transcriptomic data for ten non-model species of previously understudied animal taxa.
  • Ritari, Jarmo; Hyvärinen, Kati; Koskela, Satu; Niittyvuopio, Riitta; Nihtinen, Anne; Salmenniemi, Urpu; Putkonen, Mervi; Volin, Liisa; Kwan, Tony; Pastinen, Tomi; Itälä-Remes, Maija; Partanen, Jukka (2019)
    Genetic mismatches in protein coding genes between allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipient and donor can elicit an alloimmunity response via peptides presented by the recipient HLA receptors as minor histocompatibility antigens (mHAs). While the impact of individual mHAs on allo-HSCT outcome such as graft-vs.-host and graft-vs.-leukemia effects has been demonstrated, it is likely that established mHAs constitute only a small fraction of all immunogenic non-synonymous variants. In the present study, we have analyzed the genetic mismatching in 157 exome-sequenced sibling allo-HSCT pairs to evaluate the significance of polymorphic HLA class I associated peptides on clinical outcome. We applied computational mismatch estimation approaches based on experimentally verified HLA ligands available in public repositories, published mHAs, and predicted HLA-peptide affinites, and analyzed their associations with chronic graft-vs.-host disease (cGvHD) grades. We found that higher estimated recipient mismatching consistently increased the risk of severe cGvHD, suggesting that HLA-presented mismatching influences the likelihood of long-term complications in the patient. Furthermore, computational approaches focusing on estimation of HLA-presentation instead of all non-synonymous mismatches indiscriminately may be beneficial for analysis sensitivity and could help identify novel mHAs.
  • Beier, Sebastian; Himmelbach, Axel; Colmsee, Christian; Zhang, Xiao-Qi; Barrero, Roberto A.; Zhang, Qisen; Li, Lin; Bayer, Micha; Bolser, Daniel; Taudien, Stefan; Groth, Marco; Felder, Marius; Hastie, Alex; Simkova, Hana; Stankova, Helena; Vrana, Jan; Chan, Saki; Munoz-Amatriain, Maria; Ounit, Rachid; Wanamaker, Steve; Schmutzer, Thomas; Aliyeva-Schnorr, Lala; Grasso, Stefano; Tanskanen, Jaakko; Sampath, Dharanya; Heavens, Darren; Cao, Sujie; Chapman, Brett; Dai, Fei; Han, Yong; Li, Hua; Li, Xuan; Lin, Chongyun; McCooke, John K.; Tan, Cong; Wang, Songbo; Yin, Shuya; Zhou, Gaofeng; Poland, Jesse A.; Bellgard, Matthew I.; Houben, Andreas; Dolezel, Jaroslav; Ayling, Sarah; Lonardi, Stefano; Langridge, Peter; Muehlbauer, Gary J.; Kersey, Paul; Clark, Matthew D.; Caccamo, Mario; Schulman, Alan H.; Platzer, Matthias; Close, Timothy J.; Hansson, Mats; Zhang, Guoping; Braumann, Ilka; Li, Chengdao; Waugh, Robbie; Scholz, Uwe; Stein, Nils; Mascher, Martin (2017)
    Barley (Hordeum vulgare L.) is a cereal grass mainly used as animal fodder and raw material for the malting industry. The map-based reference genome sequence of barley cv. `Morex' was constructed by the International Barley Genome Sequencing Consortium (IBSC) using hierarchical shotgun sequencing. Here, we report the experimental and computational procedures to (i) sequence and assemble more than 80,000 bacterial artificial chromosome (BAC) clones along the minimum tiling path of a genome-wide physical map, (ii) find and validate overlaps between adjacent BACs, (iii) construct 4,265 non-redundant sequence scaffolds representing clusters of overlapping BACs, and (iv) order and orient these BAC clusters along the seven barley chromosomes using positional information provided by dense genetic maps, an optical map and chromosome conformation capture sequencing (Hi-C). Integrative access to these sequence and mapping resources is provided by the barley genome explorer (BARLEX).
  • Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Paivi; Jarvela, Irma (2016)
    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose a common genetic background for music-related creative behaviour and musical abilities at chromosome 4.