Research Core Facilities Genome Centre
Core Facilities

Genome centre

Genome Centre is a genetic analysis oriented core facility of BMC. It was created in 2005 with the goal to support the human genome research as a new and fast growing field of science in Latvia. Recognizing the importance of biobanks, necessity of advanced genetic analysis infrastructure and provision of genetic analysis related services to healthcare system, 3 specialized units were established: Biobanking unit that among others maintains Latvian Genome Database, Genotyping and sequencing unit that provides expertize and services for wide variety of genetic analyses to local scientific community and Medical genetics unit that develops, adopts and provides genetic tests to doctors and patients within the scope of Latvian healthcare system.

Biobanking Unit

The Genome Database of the Latvian Population (LGDB) is a national biobank that collects, maintains and processes health information, data and bio-specimens donated by representatives of the Latvian population. Established in 2006 LGDB comprises bio-samples, associated phenotypic and clinical information from approximately 1.5 % of the Latvian population. It is a mixed design biobank, which includes population-based as well as disease based cohorts. Disease-focused cohorts include samples and data from patients with cardiovascular disease (I), endocrine diseases, oncologic diseases and digestive system diseases. The standard set of biosamples stored in the LGDB consists of DNA, plasma, serum and white blood cells, some cohorts are complemented with additional cancer biopsies and urine samples. Recently we also started the collection of fecal samples that are dedicated to gut microbiome studies. In 2016 Latvia became a member state of Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) and BMC’s Genome center became a local node for its activities, thus as such provides support for other local biobanks.

Genotyping and sequencing

Genotyping and sequencing unit performs variety of genetic analyses by offering technical service to research groups at BMC, both local and international research partners and biotech and diagnostic companies. Our main facilities include DNA extraction laboratory that is equipped for both manual and automatic procedures, sequencing unit that exploits capillary and next generation sequencers, genotyping unit - based on TaqMan real time PCR techniques and dedicated areas for pre-PCR and post-PCR procedures equipped with liquid handling robots.

Medical genetics unit

Medical genetics unit aims at introduction of BMC developed diagnostic procedures into routine laboratory practice. In addition to those it is also offering a number of well-known and wide-used DNA diagnostic tests to general population of Latvia. Currently the primary DNA diagnostic analyses are concerning neuromuscular and neuro-degenerative diseases, mitochondrial diseases, pharmacogenomics, lipid metabolism disorders and prognosis of leukemia progression. In addition we are frequently also performing various customized - for patient or family of patients individually designed DNA analyses that are of high importance for rare disease diagnostics, segregation and prenatal analyses.

Provided services:

Biobanking Unit

  • Consultations on Biobank establishment and management in accordance with Good practice principles;
  • Consultations on organization of high quality biological sample acquisition;
  • Consultations on design of genetic studies;
  • Consultations on evaluation of research related ethical aspects;
  • Acquisition of High quality biological samples;
  • Storage and maintenance of sample collections in low and ultra-low temperature conditions;
  • Provision of LGDB samples and related data for research purposes;
  • Acquisition of LGDB sample related data from State healthcare system’s databases and registries;

 

Genotyping and sequencing Unit

  • Sanger Sequencing (any region of any genome);
  • Next Generations sequencing employing IonTorrent technology (small genome sequencing; metagenome sequencing; targeted resequencing; prokaryote 16S rRNA gene population analysis; eucaryote 18S rRNA gene population analysis; etc. ...);
  • Nucleic acid extraction from variety of biological samples;
  • Genotyping employing TaqMan real-time PCR technology;

 

Medical genetics unit

  • Analysis of CTG repeat length variation in the DMPK gene(MIOTONIC DYSTROPHY TYPE-1)
  • Analysis of CCTG repeat length variation in the ZNF9 gene (MIOTONIC DYSTROPHY TYPE-2)
  • Sequencing of exons 5 and 23 in the CLCN1 gene (THOMSEN OR BECKER MYOTONIA)
  • Sequencing of exons 1 and 2 in the CAV3 gene (LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE-1C)
  • Detection of c.550delA mutation in the CAPN3 gene (LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE-2A)
  • Detection of c.826C>A mutation in the FKRP gene (LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE-2I)
  • Analysis of CAG repeat length variation in the ATXN1 gene (SPINOCEREBELLAR ATAXIA TYPE-1)
  • Analysis of CAG repeat length variation in the ATXN2 gene (SPINOCEREBELLAR ATAXIA TYPE-2)
  • Analysis of CAG repeat length variation in the ATXN3 gene (SPINOCEREBELLAR ATAXIA TYPE-3)
  • Analysis of CAG repeat length variation in the CACNA1A gene (SPINOCEREBELLAR ATAXIA TYPE-6)
  • Next generation sequencing analysis of exons in the LDLR, APOB, PCSK9 un LDLRAP1 genes (FAMILIAL HYPERCHOLESTEROLEMIA)
  • Sequencing of exons 10, 11, 13 – 16 in the RET gene (MULTIPLE ENDOCRINE NEOPLASIA)
  • Genotyping of CYP2C9, VKORC and CYP4F2 genes (WARFARIN METABOLISM TEST)
  • Sequencing of exons 3, 8 and 9 in the PTPN11 gene (NOONAN, LEOPARD SYNDROME)
  • Sequencing of exon 13 in the PTPN11 gene (JUVENILE MYELOMONOCYTIC LEUKEMIA)
  • Sequencing of exons 3 and 4 in the MECP2 gene (RETT SYNDROME)
  • Sequencing of exons 1 and 2 in the MECP2 gene (RETT SYNDROME)
  • Detection of mutation c.860_863dupTCTG in the NPM1 gene and mutations in FLT3 gene ITD (for patients of ACUTE MYELOID LEUKEMIA)
  • Whole mtDNA sequencing (MITOCHONDRIAL PATHOLOGY).

 

Equipment:

  • ULTF 420® ultra low temperature freezer (ARCTIKO)
  • ABI PRISM 3130xl Genetic Analyzer (ThermoFisher Scientific);
  • IonTorrent PGM System for Next-Generation Sequencing (ThermoFisher Scientific);
  • IonProton System for Next-Generation Sequencing (ThermoFisher Scientific);
  • ViiA7 Real-Time PCR System (ThermoFisher Scientific);
  • Freedom EVO Liquid Handling System (Tecan);
  • GeneAmp® PCR System 9700 (Applied Biosystems);
  • Veriti™ 96-Well Thermal Cycler (Applied Biosystems);
  • KingFisher Duo Magnetic Purification System (ThermoFisher Scientific);
  • Agilent 2100 Bioanalyser (Agilent);
  • BluePippin Automated DNA Size Selection System (Sage Science);
  • RX Imola, an Automated clinical chemistry analyser (Randox);
  • S220 Focused-ultrasonicator (Covaris);
  • AutoFlex™ MALDI-TOF Mass Spectrometer (Bruker Daltocnics).

 

Publication:

1.         Rovite V, Wolff-Sagi Y, Zaharenko L, Nikitina-Zake L, Grens E, Klovins J. Genome Database of the Latvian Population (LGDB): design, goals, and primary results. Journal of Epidemiology. Accepted August 6th, 2017, in press.

2.         Dujic, T., Zhou, K., Yee, S.W., van Leeuwen N., de Keyser, C.E., Javorský, M., Goswami, S., Zaharenko. L., Marie, M., Christensen, H., Out, M., Tavendale, R., Kubo, M., Hedderson, M.M., van der Heijden, A.A., Klimčáková, L., Pirags, V., Kooy, A., Brøsen, K., Klovins, J., Semiz, S., Tkáč, I., Stricker, B.H., Palmer, C.N., 't Hart, L.M., Giacomini, K.M., Pearson, E.R. Variants in Pharmacokinetic Transporters and Glycaemic Response to Metformin: A MetGen Meta-Analysis (2016) Clinical Pharmacology & Therapeutics, Epub ahead of print. PMID: 27859023

3.         Zaharenko, L., Kalnina, I., Geldnere, K., Konrade, I., Grinberga, S., Židzik, J., Javorský, M., Lejnieks, A., Nikitina-Zake, L., Fridmanis, D., Peculis, R., Radovica-Spalvina, I., Hartmane, D., Pugovics, O., Tká, I., Klimáková, L., Pirags, V., Klovins, J. Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-Term response to metformin monotherapy in type 2 diabetes mellitus patients (2016) European Journal of Endocrinology, 175 (6), pp. 531-540.  PMID: 27609360

4.         Peculis, R., Balcere, I., Rovite, V., Megnis, K., Valtere, A., Stukens, J., Arnicane, L., Nikitina-Zake, L., Lejnieks, A., Pirags, V., Klovins, J. Polymorphisms in MEN1 and DRD2 genes are associated with the occurrence and characteristics of pituitary adenomas (2016) European Journal of Endocrinology, 175 (2), pp. 145-153. PMID: 27185868

5.         Franke B, van Hulzen KJE, Arias-Vasquez A, Bralten J, Hoogman M, et al. 2016. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept (2016) Nature Neuroscience, 19(3):420-31. PMID: 26854805

6.         J. Klovins in Schizophrenia Working Group of the Psychiatric Genomics Consortium

7.         Sekar, A., Bialas, A.R., de Rivera, H., Davis, A., Hammond, T.R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., Genovese, G., Rose, S.A., Handsaker, R.E., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly, M.J., Carroll, M.C., Stevens, B., McCarroll, S.A. Schizophrenia risk from complex variation of complement component 4 (2016). Nature, 530(7589):177-83. PMID: 26814963

8.         Bigdeli, T.B., Ripke, S., Bacanu, S.A., Lee, S.H., Wray, N.R., Gejman, P.V., Rietschel, M., Cichon, S., St Clair, D., Corvin, A., Kirov, G., McQuillin, A., Gurling, H., Rujescu, D., Andreassen, O.A., Werge, T., Blackwood, D.H., Pato, C.N., Pato, M.T., Malhotra, A.K., O'Donovan, M.C., Kendler, K.S., Fanous, A.H., Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness (2016) American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 171B (2):276-89. PMID: 26663532

9.         Hamdi, Y., .... Tihomirova, L., ..... Simard, J. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3. (2016) Breast Cancer Research and Treatment, pp. 1-18. PMID: 27796716

10.       Lawrenson, K., … Tihimirova, L., ... Price, M. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus (2016) Nature Communications, 7, art. no. 12675. PMID: 27601076

11.       Couch, F.J.,…, Tihomirova, L., …. Antoniou, A.C. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer (2016) Nature Communications, 7, art. no. 11375. PMID:     27117709

12.       Inashkina, I., Jankevics, E., Stavusis, J., Vasiljeva, I., Viksne, K., Micule, I., Strautmanis, J., Naudina, M.S., Cimbalistiene, L., Kucinskas, V., Krumina, A., Utkus, A., Burnyte, B., Matuleviciene, A., Lace, B. Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies (2016) BMC Musculoskeletal Disorders, 17 (1), art. no. 1058. PMID: 27142102

13.       Igumnova, V., Capligina, V., Krams, A., Cirule, A., Elferts, D., Pole, I., Jansone, I., Bandere, D., Ranka, R. Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients (2016) Journal of Infection and Chemotherapy, 22 (7), pp. 472-477. PMID: 27236516

14.       McLaughlin RL, Schijven D, van Rheenen W, van Eijk KR, O'Brien M, Kahn RS, Ophoff RA, Goris A, Bradley DG, Al-Chalabi A, van den Berg LH, Luykx JJ, Hardiman O, Veldink JH; Project MinE GWAS Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. (2017) Nat Commun. Mar 21;8:14774.

15.       Zhou K, Yee SW, Seiser EL, van Leeuwen N, Tavendale R, Bennett AJ, Groves CJ, Coleman RL, van der Heijden AA, Beulens JW, de Keyser CE, Zaharenko L, Rotroff DM, Out M, Jablonski KA, Chen L, Javorský M, Židzik J, Levin AM, Williams LK, Dujic T, Semiz S, Kubo M, Chien HC, Maeda S, Witte JS, Wu L, Tkáč I, Kooy A, van Schaik RHN, Stehouwer CDA, Logie L; MetGen Investigators; DPP Investigators; ACCORD Investigators, Sutherland C, Klovins J, Pirags V, Hofman A, Stricker BH, Motsinger-Reif AA, Wagner MJ, Innocenti F, 't Hart LM, Holman RR, McCarthy MI, Hedderson MM, Palmer CNA, Florez JC, Giacomini KM, Pearson ER. Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. (2016) Nat Genet. 2016 Sep;48(9):1055-1059.

 

Vita Rovīte , Dr. biol.

Researcher
Phone: +371 67808200
E-mail: vita.rovite@biomed.lu.lv

Biobanking Unit

 

Dāvids Fridmanis , Dr. biol.

Senior researcher
Phone: +371 67473083
E-mail: davids@biomed.lu.lv

Genotyping and sequencing

 

Inna Iņaškina , Dr. biol.

Senior researcher
Phone: +371 67808210
E-mail: inna@biomed.lu.lv

Medical genetics unit

Quick links



Mājas lapas izstrādi finansēja ERAF 2.1.1.2. aktivitātes projekts Nr. 2010/0196/2DP/2.1.1.2.0/10/APIA/VIAA/004 "Latvijas biomedicīnas pētījumu integrācija Eiropas zinātnes telpā".