TUHAT-artikkelit / Articles from TUHAT CRIS


Kokoelma sisältää TUHAT-tutkimustietojäjestelmän kautta tallennetut Open Access-artikkelit.

Helsingin yliopiston tutkijat voivat rinnakkaistallentaa tutkimusjulkaisujansa HELDAan liittämällä kokotekstin julkaisuun TUHAT-tutkimustietojärjestelmässä. (Toimintaohje tutkijalle)

This collection contains Open Access articles deposited from the University of Helsinki TUHAT CRIS

Uusimmat julkaisut

  • Wallström, Peter; Drake, Isabel; Sonestedt, Emily; Gullberg, Bo; Bjartell, Anders; Olsson, Håkan; Adlercreutz, Herman; Tikkanen, Matti J.; Wirfält, Elisabet (2018)
    Enterolactone (ENL) is formed in the human gut after consumption of lignans, has estrogenic properties, and has been associated with risk of prostate cancer. We examined the association between plasma ENL levels and prostate cancer in a nested case-control study within the population-based Malmo Diet and Cancer cohort. We also examined the association between plasma ENL and dietary and lifestyle factors. The study population consisted of 1010 cases occurring during a mean follow-up of 14.6 years, and 1817 controls matched on age and study entry date. We used national registers (95%) and hospital records (5%) to ascertain cases. Diet was estimated by a modified diet history method. Plasma ENL concentrations were determined by a time-resolved fluoroimmunoassay. Odds ratios were calculated by unconditional logistic regression. There were no significant associations between plasma ENL and incidence of all prostate cancer (odds ratio 0.99 [95% confidence interval 0.77-1.280] for the highest ENL quintile versus lowest, p for trend 0.66). However, in certain subgroups of men, including men with abdominal obesity (p for interaction = 0.012), we observed associations between high ENL levels and lower odds of high-risk prostate cancer. Plasma ENL was positively associated with consumption of high-fibre bread, fruit, tea, and coffee; with age, and with height, while it was negatively associated with smoking and waist circumference; however, although significant, all associations were rather weak (r ae |0.14|). ENL concentration was not consistently associated with lower prostate cancer risk, although it was weakly associated with a healthy lifestyle.
  • Matikainen, M.; Aro, E.; Vironen, J.; Kössi, J.; Hulmi, T.; Silvasti, S.; Ilves, I.; Hertsi, M.; Mustonen, K.; Paajanen, H. (2018)
    Chronic pain after inguinal hernioplasty is the foremost side-effect up to 10-30% of patients. Mesh fixation may influence on the incidence of chronic pain after open anterior mesh repairs. Some 625 patients who underwent open anterior mesh repairs were randomized to receive one of the three meshes and fixations: cyanoacrylate glue with low-weight polypropylene mesh (n = 216), non-absorbable sutures with partially absorbable mesh (n = 207) or self-gripping polyesther mesh (n = 202). Factors related to chronic pain (visual analogue scores; VAS ae 30, range 0-100) at 1 year postoperatively were analyzed using logistic regression method. A second analysis using telephone interview and patient records was performed 2 years after the index surgery. At index operation, all patient characteristics were similar in the three study groups. After 1 year, chronic inguinal pain was found in 52 patients and after 2 years in only 16 patients with no difference between the study groups. During 2 years' follow-up, three (0.48%) patients with recurrences and five (0.8%) patients with chronic pain were re-operated. Multivariate regression analysis indicated that only new recurrent hernias and high pain scores at day 7 were predictive factors for longstanding groin pain (p = 0.001). Type of mesh or fixation, gender, pre-operative VAS, age, body mass index or duration of operation did not predict chronic pain. Only the presence of recurrent hernia and early severe pain after index operation seemed to predict longstanding inguinal pain.
  • Hyytiäinen, Heli K.; Mölsä, Sari H.; Junnila, Jouni J. T.; Laitinen-Vapaavuori, Outi M.; Hielm-Björkman, Anna K. (2018)
    This study aimed at developing a quantitative testing battery for dogs' stifle functionality, as, unlike in human medicine, currently none is available in the veterinary field. Forty-three dogs with surgically treated unilateral cranial cruciate ligament rupture and 21 dogs with no known musculoskeletal problems were included. Eight previously studied tests: compensation in sitting and lying positions, symmetry of thrust in hindlimbs when rising from lying and sitting, static weight bearing, stifle flexion and extension and muscle mass symmetry, were summed into the Finnish Canine Stifle Index (FCSI). Sensitivities and specificities of the dichotomised FCSI score were calculated against orthopaedic examination, radiological and force platform analysis and a conclusive assessment (combination of previous). One-way analysis of variance (ANOVA)was used to evaluate FCSI score differences between the groups. Cronbach's alpha for internal consistency was calculated. The range of the index score was 0-263, with a proposed cut-off value of 60 between 'adequate' and 'compromised' functional performance. In comparison to the conclusive assessment, the sensitivity and specificity of the FCSI were 90 per cent and 90.5 per cent, respectively. Cronbach's alpha for internal reliability of the FCSI score was 0.727. An estimate of the surgically treated and control dogs' FCSI scores were 105 (95 per cent CI 93 to 116) and 20 (95 per cent CI 4 to 37), respectively. The difference between the groups was significant (P
  • Mattila, K.; Haas, M.; Haikala, L. K.; Jo, Y-S.; Lehtinen, K.; Leinert, Ch.; Väisänen, P. (2018)
    Context. Dark nebulae display a surface brightness because dust grains scatter light of the general interstellar radiation field (ISRF). High-galactic-latitudes dark nebulae are seen as bright nebulae when surrounded by transparent areas which have less scattered light from the general galactic dust layer. Aims. Photometry of the bright dark nebulae LDN 1780, LDN 1642, and LBN 406 shall be used to derive scattering properties of dust and to investigate the presence of UV fluorescence emission by molecular hydrogen and the extended red emission (ERE). Methods. We used multi-wavelength optical photometry and imaging at ground-based telescopes and archival imaging and spectroscopic UV data from the spaceborn GALEX and SPEAR/FIMS instruments. In the analysis we used Monte Carlo RT and both observational data and synthetic models for the ISRF in the solar neighbourhood. The line-of-sight extinctions through the clouds have been determined using near infrared excesses of background stars and the 200/250 mu m far infrared emission by dust as measured using the ISO and Herschel space observatories. Results. The optical surface brightness of the three target clouds can be explained in terms of scattered light. The dust albedo ranges from similar to 0.58 at 3500 angstrom to similar to 0.72 at 7500 angstrom. The spectral energy distribution of LDN 1780 is explained in terms of optical depth and background scattered light effects instead of the original published suggestion in terms of ERE. The far-ultraviolet surface brightness of LDN 1780 cannot be explained by scattered light only. In LDN 1780, H-2 fluorescent emission in the wavelength range 1400-1700 angstrom has been detected and analysed. Conclusions. Our albedo values are in good agreement with the predictions of the dust model of Weingartner and Draine and with the THEMIS CMM model for evolved core-mantle grains. The distribution of H-2 fluorescent emission in LDN 1780 shows a pronounced dichotomy with a strong preference for its southern side where enhanced illumination is impinging from the Sco OB2 association and the O star zeta Oph. A good correlation is found between the H-2 fluorescence and a previously mapped 21-cm excess emission. The H-2 fluorescence emission in LDN 1780 has been modelled using a PDR code; the resulting values for H-2 column density and the total gas density are consistent with the estimates derived from CO observations and optical extinction along the line of sight.
  • Koponen, Juhani (Manchester University Press, 2014)
    Studies in Imperialism
    Shows the variety of meanings of development in South-Eastern Tanganyika during the period concerned and spells out their implications for the history of development more generally
  • Hokynar, Kati; Salava, Alexander; Vesterinen, Eero; Lauerma, Antti; Ranki, Annamari; Puolakkainen, Mirja (2018)
  • Evangelou, Evangelos; Warren, Helen R.; Mosen-Ansorena, David; Mifsu, Borbala; Pazoki, Raha; Gao, He; Ntritsos, Georgios; Dimou, Niki; Cabrer, Claudia P.; Karaman, Ibrahim; Ng, FuLiang; Evangelou, Marina; Witkowska, Katarzyna; Tzanis, Evan; Hellwege, Jacklyn N.; Giri, Ayush; Edwards, Digna R. Velez; Sun, Yan; Cho, Kelly; Gaziano, J. Michael; Wilson, Peter W. F.; Tsao, Philip S.; Kovesdy, Csaba P.; Esko, Tonu; Magi, Reedik; Milani, Lili; Almgren, Peter; Boutin, Thibaud; Debette, Stephanie; Ding, Jun; Giulianini, Franco; Holliday, Elizabeth G.; Jackson, Anne U.; Li-Gao, Ruifang; Lin, Wei-Yu; Luan, Jian'an; Mangino, Massimo; Oldmeadow, Christopher; Prins, Bram Peter; Qian, Yong; Sargurupremraj, Muralidharan; Shah, Nabi; Havulinna, Aki S.; Jousilahti, Pekka; Kristiansson, Kati; Palotie, Aarno; Perola, Markus; Ripatti, Samuli; Sarin, Antti-Pekka; Tuomilehto, Jaakko (2018)
    High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
  • Soukkio, Paula; Suikkanen, Sara; Kääriä, Sanna; Kautiainen, Hannu; Sipilä, Sarianna; Kukkonen-Harjula, Katriina; Hupli, Markku (2018)
    Background: Health concerns, such as frailty and osteoporotic fractures decrease functional capacity and increase use of health and social care services in the aging population. The ability to continue living at home is dependent on functional capacity, which can be enhanced by rehabilitation. We study the effects of a 12-month home-based physiotherapy program with 12-month follow-up on duration of living at home, functional capacity, and the use of social and health care services among older persons with signs of frailty, or with a recently operated hip fracture. Methods: This is a non-blinded, parallel group, randomized controlled trial performed in South Karelia Social and Health Care District, Finland (population 131,000). Three hundred community-dwelling older persons with signs of frailty (age >= 65) and 300 persons with a recent hip fracture (age >= 60) will be recruited. Frailty is screened by FRAIL questionnaire and verified by modified Fried's frailty criteria. Both patient groups will be randomized separately to a physiotherapy and a usual care arm. Individualized, structured and progressive physiotherapy will be carried out for 60 min, twice a week for 12 months at the participant's home. The primary outcome at 24 months is duration of living at home. Our hypothesis is that persons assigned to the physiotherapy arm will live at home for six months longer than those in the usual care arm. Secondary outcomes are functional capacity, frailty status, health-related quality-of-life, falls, use and costs of social and health care services, and mortality. Assessments, among others Short Physical Performance Battery, Functional Independence Measure, Mini Nutritional Assessment, and Mini-Mental State Examination will be performed at the participant's home at baseline, 3, 6, and 12 months. Register data on the use and costs of social and health care services, and mortality will be monitored for 24 months. Discussion: Our trial will provide new knowledge on the potential of intensive, long-term home-based physiotherapy among older persons at risk for disabilities, to enhance functional capacity and thereby to postpone the need for institutional care, and diminish the use of social and health care services.
  • Jääskeläinen, Tiina; Kärkkäinen, Olli; Jokkala, Jenna; Litonius, Kaisa; Heinonen, Seppo; Auriola, Seppo; Lehtonen, Marko; Hanhineva, Kati; Laivuori, Hannele (2018)
    Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted meta bolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based meta bolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth.
  • GPrank 
    Topa, Hande; Honkela, Antti (2018)
    Background: Genome-wide high-throughput sequencing (HIS) time series experiments are a powerful tool for monitoring various genomic elements over time. They can be used to monitor, for example, gene or transcript expression with RNA sequencing (RNA-seq), DNA methylation levels with bisulfite sequencing (BS-seq), or abundances of genetic variants in populations with pooled sequencing (Pool-seq). However, because of high experimental costs, the time series data sets often consist of a very limited number of time points with very few or no biological replicates, posing challenges in the data analysis. Results: Here we present the GPrank R package for modelling genome-wide time series by incorporating variance information obtained during pre-processing of the HIS data using probabilistic quantification methods or from a beta-binomial model using sequencing depth. GPrank is well-suited for analysing both short and irregularly sampled time series. It is based on modelling each time series by two Gaussian process (GP) models, namely, time-dependent and time-independent GP models, and comparing the evidence provided by data under two models by computing their Bayes factor (BF). Genomic elements are then ranked by their BFs, and temporally most dynamic elements can be identified. Conclusions: Incorporating the variance information helps GPrank avoid false positives without compromising computational efficiency. Fitted models can be easily further explored in a browser. Detection and visualisation of temporally most active dynamic elements in the genome can provide a good starting point for further downstream analyses for increasing our understanding of the studied processes.
  • Almangush, Alhadi; Mäkitie, Antti A.; Mäkinen, Laura K.; Kauppila, Joonas H.; Pukkila, Matti; Hagström, Jaana; Laranne, Jussi; Soini, Ylermi; Kowalski, Luiz Paulo; Grenman, Reidar; Haglund, Caj; Coletta, Ricardo D.; Salo, Tuula; Leivo, Ilmo (2018)
    One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (ae4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.
  • Droste, Nils; D'Amato, Dalia; Goddard, Jessica J. (2018)
    We analyze how the content of ecosystem service research has evolved since the early 1990s. Conducting a computational bibliometric content analysis we process a corpus of 14,118 peer-reviewed scientific article abstracts on ecosystem services (ES) from Web of Science records. To provide a comprehensive content analysis of ES research literature, we employ a latent Dirichlet allocation algorithm. For three different time periods (1990-2000, 2001-2010, 2011-2016), we derive nine main ES topics arising from content analysis and elaborate on how they are related over time. The results show that natural science-based ES research analyzes oceanic, freshwater, agricultural, forest, and soil ecosystems. Pollination and land cover emerge as traceable standalone topics around 2001. Social science ES literature demonstrates a reflexive and critical lens on the role of ES research and includes critiques of market-oriented perspectives. The area where social and natural science converge most is about land use systems such as agriculture. Overall, we provide evidence of the strong natural science foundation, the highly interdisciplinary nature of ES research, and a shift in social ES research towards integrated assessments and governance approaches. Furthermore, we discuss potential reasons for observable topic developments.
  • Kämäräinen, A.; Simojoki, A.; Linden, L.; Jokinen, K.; Silvan, N. (2018)
    The surface biomass of moss dominated by Sphagnum fuscum (Schimp.) Klinggr. (Rusty Bog-moss) was harvested from a sparsely drained raised bog. Physical properties of the Sphagnum moss were determined and compared with those of weakly and moderately decomposed peats. Water retention curves (WRC) and saturated hydraulic conductivities (K-s) are reported for samples of Sphagnum moss with natural structure, as well as for samples that were cut to selected fibre lengths or compacted to different bulk densities. The gravimetric water retention results indicate that, on a dry mass basis, Sphagnum moss can hold more water than both types of peat under equal matric potentials. On a volumetric basis, the water retention of Sphagnum moss can be linearly increased by compacting at a gravimetric water content of 2 (g water / g dry mass). The bimodal water retention curve of Sphagnum moss appears to be a consequence of the natural double porosity of the moss matrix. The 6-parameter form of the double-porosity van Genuchten equation is used to describe the volumetric water retention of the moss as its bulk density increases. Our results provide considerable insight into the physical growing media properties of Sphagnum moss biomass.
  • Rosa, Elena; Woestmann, Luisa; Biere, Arjen; Saastamoinen, Marjo (2018)
    Host plant chemical composition critically shapes the performance of insect herbivores feeding on them. Some insects have become specialized on plant secondary metabolites, and even use them to their own advantage such as defense against predators. However, infection by plant pathogens can seriously alter the interaction between herbivores and their host plants. We tested whether the effects of the plant secondary metabolites, iridoid glycosides (IGs), on the performance and immune response of an insect herbivore are modulated by a plant pathogen. We used the IG-specialized Glanville fritillary butterfly Melitaea cinxia, its host plant Plantago lanceolata, and the naturally occurring plant pathogen, powdery mildew Podosphaera plantaginis, as model system. Pre-diapause larvae were fed on P. lanceolata host plants selected to contain either high or low IGs, in the presence or absence of powdery mildew. Larval performance was measured by growth rate, survival until diapause, and by investment in immunity. We assessed immunity after a bacterial challenge in terms of phenoloxidase (PO) activity and the expression of seven pre-selected insect immune genes (qPCR). We found that the beneficial effects of constitutive leaf IGs, that improved larval growth, were significantly reduced by mildew infection. Moreover, mildew presence downregulated one component of larval immune response (PO activity), suggesting a physiological cost of investment in immunity under suboptimal conditions. Yet, feeding on mildew-infected leaves caused an upregulation of two immune genes, lysozyme and prophenoloxidase. Our findings indicate that a plant pathogen can significantly modulate the effects of secondary metabolites on the growth of an insect herbivore. Furthermore, we show that a plant pathogen can induce contrasting effects on insect immune function. We suspect that the activation of the immune system toward a plant pathogen infection may be maladaptive, but the actual infectivity on the larvae should be tested.
  • Hellen, Heidi; Praplan, Arnaud P.; Tykkä, Toni; Ylivinkka, Ilona; Vakkari, Ville; Bäck, Jaana; Petäjä, Tuukka; Kulmala, Markku; Hakola, Hannele (2018)
    The concentrations of terpenoids (isoprene; monoterpenes, MTs; and sesquiterpenes, SQTs) and oxygenated volatile organic compounds (OVOCs; i.e. aldehydes, alcohols, acetates and volatile organic acids, VOAs) were investigated during 2 years at a boreal forest site in Hyytiala, Finland, using in situ gas chromatograph mass spectrometers (GC-MSs). Seasonal and diurnal variations of terpenoid and OVOC concentrations as well as their relationship with meteorological factors were studied. Of the VOCs examined, C-2-C-7 unbranched VOAs showed the highest concentrations, mainly due to their low reactivity. Of the terpenoids, MTs showed the highest concentrations at the site, but seven different highly reactive SQTs were also detected. The monthly and daily mean concentrations of most terpenoids, aldehydes and VOAs were highly dependent on the temperature. The highest exponential correlation with temperature was found for a SQT (beta-caryophyllene) in summer. The diurnal variations in the concentrations could be explained by sources, sinks and vertical mixing. The diurnal variations in MT concentrations were strongly affected by vertical mixing. Based on the temperature correlations and mixing layer height (MLH), simple proxies were developed for estimating the MT and SQT concentrations. To estimate the importance of different compound groups and compounds in local atmospheric chemistry, reactivity with main oxidants (hydroxyl radical, OH; nitrate radical, NO3; and ozone, O-3) and production rates of oxidation products (OxPRs) were calculated. The MTs dominated OH and NO3 radical chemistry, but the SQTs greatly impacted O-3 chemistry, even though the concentrations of SQT were 30 times lower than the MT concentrations. SQTs were also the most important for the production of oxidation products. Since the SQTs show high secondary organic aerosol (SOA) yields, the results clearly indicate the importance of SQTs for local SOA production.
  • Järvi, Leena; Rannik, Üllar; Kokkonen, Tom; Kurppa, Mona; Karppinen, Ari; Kouznetsov, Rostislav D.; Rantala, Pekka; Vesala, Timo; Wood, Curtis R. (2018)
    The eddy covariance (EC) technique is the most direct method for measuring the exchange between the surface and the atmosphere in different ecosystems. Thus, it is commonly used to get information on air pollutant and greenhouse gas emissions, and on turbulent heat transfer. Typically an ecosystem is monitored by only one single EC measurement station at a time, making the ecosystem-level flux values subject to random and systematic uncertainties. Furthermore, in urban ecosystems we often have no choice but to conduct the single-point measurements in non-ideal locations such as close to buildings and/or in the roughness sub-layer, bringing further complications to data analysis and flux estimations. In order to tackle the question of how representative a single EC measurement point in an urban area can be, two identical EC systems - measuring momentum, sensible and latent heat, and carbon dioxide fluxes - were installed on each side of the same building structure in central Helsinki, Finland, during July 2013-September 2015. The main interests were to understand the sensitivity of the vertical fluxes on the single measurement point and to estimate the systematic uncertainty in annual cumulative values due to missing data if certain, relatively wide, flow-distorted wind sectors are disregarded. The momentum and measured scalar fluxes respond very differently to the distortion caused by the building structure. The momentum flux is the most sensitive to the measurement location, whereas scalar fluxes are less impacted. The flow distortion areas of the two EC systems (40-150 and 230-340 degrees) are best detected from the mean-wind-normalised turbulent kinetic energy, and outside these areas the median relative random uncertainties of the studied fluxes measured by one system are between 12 % and 28 %. Different gap-filling methods with which to yield annual cumulative fluxes show how using data from a single EC measurement point can cause up to a 12 % (480 g C m(-2)) underestimation in the cumulative carbon fluxes as compared to combined data from the two systems. Combining the data from two EC systems also increases the fraction of usable half-hourly carbon fluxes from 45 % to 69 % at the annual level. For sensible and latent heat, the respective underestimations are up to 5 % and 8 % (0.094 and 0.069 TJ m(-2)). The obtained random and systematic uncertainties are in the same range as observed in vegetated ecosystems. We also show how the commonly used data flagging criteria in natural ecosystems, kurtosis and skewness, are not necessarily suitable for filtering out data in a densely built urban environment. The results show how the single measurement system can be used to derive representative flux values for central Helsinki, but the addition of second system to other side of the building structure decreases the systematic uncertainties. Comparable results can be expected in similarly dense city locations where no large directional deviations in the source area are seen. In general, the obtained results will aid the scientific community by providing information about the sensitivity of EC measurements and their quality flagging in urban areas.
  • Vierros, Marja (2017)
    This article provides a new reading of a notarial signature in papyrus BGU III 997, a copy of an agoranomic sale from the Ptolemaic period. The signature was not transcribed in the original edition since only traces of it survive and the papyrus seems blank and intact at that place. A closer examination reveals that only the upper layer of the papyrus has peeled off. How, when, and why the alteration took place, remains unsolved.
  • Quitt, Pia R.; Hytönen, Marjo K.; Matiasek, Kaspar; Rosati, Marco; Fischer, Andrea; Lohi, Hannes (2018)
    An eight week old Labrador Retriever puppy presented with stiff-legged robotic gait. Abnormal gait was most evident after rest and improved with prolonged activity. On occasions, initiation of sudden movements would result in collapse with rigidity of the trunk and stiff extended limbs for several seconds. Other clinical signs were excitement-induced upper airway stridor and oropharyngeal dysphagia. Myotonia congenita was diagnosed based on clinical signs, abundant myotonic discharges on electromyography and exclusion of structural myopathies on histology. Whole exome sequencing revealed a case-specific homozygous variant in CLCN1, c.2275A > T resulting in a premature stop codon, p.R759X. The CLCN1 variant was absent from the genomes of 127 Labrador Retriever controls and 474 control dogs from other breeds. This study expands the spectrum of identified canine CLCN1 mutations and the list of affected breeds in myotonia congenita and highlights the potential value of dogs as translational large animal models of human genetic diseases.

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