NGI is one of the largest technical platforms at SciLifeLab. We provide access to technology for sequencing, genotyping and associated bioinformatics support to researchers based in Sweden.
We're thrilled to announce that we have now transitioned to exclusively using the data delivery system Data Delivery System (DDS) for all our data deliveries. DDS will now be our default system, streamlining our processes and enhancing our service.
Introduction and persistence of tularemia in Bulgaria.
K Myrtennäs, K Marinov, A Johansson, M Niemcewicz, E Karlsson, M Byström, M Forsman
Infect Ecol Epidemiol, 6 2000-8686 (2016)
Outbreaks of the zoonotic disease tularemia occurred in north-east Bulgaria in the 1960s. Then came 30 years of epidemiological silence until new outbreaks occurred in west Bulgaria in the 1990s. To investigate how bacterial strains of Francisella tularensis causing tularemia in wildlife and humans in the 1960s and the 1990s were related, we explored their genetic diversity.
Ten F. tularensis genomes from the 1960s (n=3) and the 1990s (n=7) were sequenced, assigned to canonical single-nucleotide polymorphism (canSNP) clades, and compared to reference genomes. We developed four new canSNP polymerase chain reaction (PCR) assays based on the genome sequence information.
The genetic analysis showed that the outbreaks in the 1960s as well as in the 1990s involved multiple clones and new genetic diversity. The smallest genetic difference found between any of the Bulgarian strains was five SNPs between the strains L2 and 81 isolated 43 years apart, indicating that F. tularensis may persist locally over long time periods without causing outbreaks. The existence of genetically highly similar strain-pairs isolated the same year in the same area from different hosts supports a hypothesis of local expansion of clones during outbreaks. Close relationship (two SNPs) was found between one strain isolated 1961 in northeast Bulgaria and one strain isolated 5 years before in USSR. Historical data coinciding with the actual time point describe the introduction of water rats from USSR into the Bulgarian outbreak area, which may explain the close genetic relationship and the origin of the outbreak.
Genome analysis of strains from two outbreaks in the 1960s and the 1990s provided valuable information on the genetic diversity and persistence of F. tularensis in Bulgaria.
Contribution of different dispersal sources to the metabolic response of lake bacterioplankton following a salinity change.
J Comte, S Langenheder, M Berga, ES Lindström
Environ. Microbiol., 19 (1) 1462-2920 (2017)
Dispersal can modify how bacterial community composition (BCC) changes in response to environmental perturbations, yet knowledge about the functional consequences of dispersal is limited. Here we hypothesized that changes in bacterial community production in response to a salinity disturbance depend on the possibility to recruit cells from different dispersal sources. To investigate this, we conducted an in situ mesocosm experiment where bacterial communities of an oligotrophic lake were exposed to different salinities (0, 18, 36 psu) for 2 weeks and subjected to dispersal of cells originating from sediments, air (mesocosms open to air deposition), both or none. BCC was determined using 454 pyrosequencing of the 16S rRNA gene and bacterial production was measured by (3) H leucine uptake. Bacterial production differed significantly among salinity treatments and dispersal treatments, being highest at high salinity. These changes were associated with changes in BCC and it was found that the identity of the main functional contributors differed at different salinities. Our results further showed that after a salinity perturbation, the response of bacterial communities depended on the recruitment of taxa, including marine representatives (e.g., Alphaproteobacteria Loktanella, Erythrobacter and the Gammaproteobacterium Rheiheimera) from dispersal sources, in which atmospheric deposition appeared to play a major role.
Novel Mutation m.10372A>G in MT-ND3 Causing Sensorimotor Axonal Polyneuropathy.
H Bruhn, K Samuelsson, FA Schober, M Engvall, N Lesko, R Wibom, I Nennesmo, J Calvo-Garrido, R Press, H Stranneheim, C Freyer, A Wedell, A Wredenberg
Neurol Genet, 7 (2) 2376-7839 (2021)
To investigate the pathogenicity of a novel MT-ND3 mutation identified in a patient with adult-onset sensorimotor axonal polyneuropathy and report the clinical, morphologic, and biochemical findings.
Clinical assessments and morphologic and biochemical investigations of skeletal muscle and cultured myoblasts from the patient were performed. Whole-genome sequencing (WGS) of DNA from skeletal muscle and Sanger sequencing of mitochondrial DNA (mtDNA) from both skeletal muscle and cultured myoblasts were performed. Heteroplasmic levels of mutated mtDNA in different tissues were quantified by last-cycle hot PCR.
Muscle showed ragged red fibers, paracrystalline inclusions, a significant reduction in complex I (CI) respiratory chain (RC) activity, and decreased adenosine triphosphate (ATP) production for all substrates used by CI. Sanger sequencing of DNA from skeletal muscle detected a unique previously unreported heteroplasmic mutation in mtDNA encoded MT-ND3, coding for a subunit in CI. WGS confirmed the mtDNA mutation but did not detect any other mutation explaining the disease. Cultured myoblasts, however, did not carry the mutation, and RC activity measurements in myoblasts were normal.
We report a case with adult-onset sensorimotor axonal polyneuropathy caused by a novel mtDNA mutation in MT-ND3. Loss of heteroplasmy in blood, cultured fibroblasts and myoblasts from the patient, and normal measurement of RC activity of the myoblasts support pathogenicity of the mutation. These findings highlight the importance of mitochondrial investigations in patients presenting with seemingly idiopathic polyneuropathy, especially if muscle also is affected.
Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia.
S Teppo, S Laukkanen, T Liuksiala, J Nordlund, M Oittinen, K Teittinen, T Grönroos, P St-Onge, D Sinnett, AC Syvänen, M Nykter, K Viiri, M Heinäniemi, O Lohi
Approximately 20%-25% of childhood acute lymphoblastic leukemias carry the ETV6-RUNX1 (E/R) fusion gene, a fusion of two central hematopoietic transcription factors, ETV6 (TEL) and RUNX1 (AML1). Despite its prevalence, the exact genomic targets of E/R have remained elusive. We evaluated gene loci and enhancers targeted by E/R genome-wide in precursor B acute leukemia cells using global run-on sequencing (GRO-seq). We show that expression of the E/R fusion leads to widespread repression of RUNX1 motif-containing enhancers at its target gene loci. Moreover, multiple super-enhancers from the CD19+/CD20+-lineage were repressed, implicating a role in impediment of lineage commitment. In effect, the expression of several genes involved in B cell signaling and adhesion was down-regulated, and the repression depended on the wild-type DNA-binding Runt domain of RUNX1. We also identified a number of E/R-regulated annotated and de novo noncoding genes. The results provide a comprehensive genome-wide mapping between E/R-regulated key regulatory elements and genes in precursor B cell leukemia that disrupt normal B lymphopoiesis.
Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes.
Y Qu, A Lennartsson, VI Gaidzik, S Deneberg, M Karimi, S Bengtzén, M Höglund, L Bullinger, K Döhner, S Lehmann
Epigenetics, 9 (8) 1559-2308 (2014)
The extent and role of aberrant DNA methylation in promoter CpG islands (CGIs) have been extensively studied in leukemia and other malignancies. Still, CGIs represent only a small fraction of the methylome. We aimed to characterize genome-wide differential methylation of cytogenetically normal AML (CN-AML) cells compared with normal CD34(+) bone marrow cells using the Illumina 450K methylation array. Differential methylation in CN-AML was most prominent in genomic areas far from CGIs, in so called open sea regions. Furthermore, differential methylation was specifically found in genes encoding transcription factors (TFs), with WT1 being the most differentially methylated TF. Among genetic mutations in AML, DNMT3A mutations showed the most prominent association with the DNA methylation pattern, characterized by hypomethylation of CGIs (as compared with DNMT3A wild type cases). The differential methylation in DNMT3A mutant cells vs. wild type cells was predominantly found in HOX genes, which were hypomethylated. These results were confirmed and validated in an independent CN-AML cohort. In conclusion, we show that, in CN-AML, the most pronounced changes in DNA methylation occur in non-CGI regions and that DNMT3A mutations confer a pattern of global hypomethylation that specifically targets HOX genes.
Combinations of Genetic Data Present in Bipolar Patients, but Absent in Control Persons.
E Mellerup, OA Andreassen, B Bennike, H Dam, S Djurovic, T Hansen, MB Jorgensen, LV Kessing, P Koefoed, I Melle, O Mors, T Werge, GL Moeller
PLoS ONE, 10 (11) 1932-6203 (2015)
The main objective of the study was to find combinations of genetic variants significantly associated with bipolar disorder. In a previous study of bipolar disorder, combinations of three single nucleotide polymorphism (SNP) genotypes taken from 803 SNPs were analyzed, and four clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of four SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the four previous clusters were identified in the genomes of 209 of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.
Exploring rare and low-frequency variants in the Saguenay-Lac-Saint-Jean population identified genes associated with asthma and allergy traits.
A Morin, AM Madore, T Kwan, M Ban, J Partanen, L Rönnblom, AC Syvänen, S Sawcer, H Stunnenberg, M Lathrop, T Pastinen, C Laprise
NGI CollaborationEur. J. Hum. Genet., 27 (1) 1476-5438 (2019)
The Saguenay-Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and is known for its unique demographic history and founder effect. As founder populations are enriched with population-specific variants, we characterized the variants distribution in SLSJ and compared it with four European populations (Finnish, Sweden, United Kingdom and France), of which the Finnish population is another founder population. Targeted sequencing of the coding and non-coding immune regulatory regions of the SLSJ asthma familial cohort and the four European populations were performed. Rare and low-frequency coding and non-coding regulatory variants identified in the SLSJ population were then investigated for variant- and gene-level associations with asthma and allergy-related traits (eosinophil percentage, immunoglobulin (Ig) E levels and lung function). Our data showed that (1) rare or deleterious variants were not enriched in the two founder populations as compared with the three non-founder European populations; (2) a larger proportion of founder population-specific variants occurred with higher frequencies; and (3) low-frequency variants appeared to be more deleterious. Furthermore, a rare variant, rs1386931, located in the 3'-UTR of CXCR6 and intron of FYCO1 was found to be associated with eosinophil percentage. Gene-based analyses identified NRP2, MRPL44 and SERPINE2 to be associated with various asthma and allergy-related traits. Our study demonstrated the usefulness of using a founder population to identify new genes associated with asthma and allergy-related traits; thus better understand the genes and pathways implicated in pathophysiology.
Last Updated: 25th February 2024
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