Browsing by Author "Reimann, Ene"

Now showing 1 - 7 of 7

Analysis of repetitive element expression in the blood and skin of patients with Parkinson’s disease identifies differential expression of satellite elements
(Nature, 2019-03-13) Billingsley, Kimberley J.; Lättekivi, Freddy; Planken, Anu; Reimann, Ene; Kurvits, Lille; Kadastik-Eerme, Liis; Kasterpalu, Kristjan M.; Bubb, Vivien J.; Quinn, John P.; Kõks, Sulev; Taba, Pille
Repetitive elements (RE) constitute the majority of the human genome and have a range of functions both structural and regulatory on genomic function and gene expression. RE overexpression has been observed in several neurodegenerative diseases, consistent with the observation of aberrant expression of RE posing a mutagenic threat. Despite reports that associate RE expression with PD no study has comprehensively analyzed the role of these elements in the disease. This study presents the frst genome-wide analysis of RE expression in PD to date. Analysis of RNA-sequencing data of 12 PD patients and 12 healthy controls identified tissue-specific expression differences and more significantly, differential expression of four satellite elements; two simple satellite III (repName=CATTC_n and _GAATG_n) a high-copy satellite II (HSATII) and a centromeric satellite (ALR_Alpha) in the blood of PD patients. In support of the growing body of recent evidence associating REs with neurodegenerative disease, this study highlights the potential importance of characterization of RE expression in such diseases
C14orf132 gene is possibly related to extremely low birth weight
(2016-09) Tiirats, Airi; Viltrop, Triin; Nõukas, Margit; Reimann, Ene; Salumets, Andres; Kõks, Sulev
Background Despite extensive research the genetic component of extremely low birth weight (ELBW) in newborns has remained obscure. Results The aim of the case study was to identify candidate gene(s) causing ELBW in newborns and hypotrophy in infants. A family of four was studied: mother, father and two ELBW-phenotype children. Studies were made of the medical conditions of the second child at birth and post-partum - peculiar phenotype, micro-anomalies, recurrent infections, suspicion of autoimmune hepatitis, multifactorial encephalopathy and suspected metabolic and chromosomal abnormalities. Whole genome single nucleotide polymorphism (SNP) genotyping array was used to investigate the genomic rearrangements in both affected children using peripheral blood DNA samples. Whole blood transcriptome was assessed by using RNA sequencing (RNA-seq) in all four family members. RNA-seq identified a single gene – C14orf132 (chromosome 14 open reading frame 132) differentially expressed, with the level of the transcript significantly lower in the blood samples of the children. Copy number variant (CNV) analysis did not reveal any pathogenic CNVs in the region of C14orf132 gene of both affected children. Conclusion We demonstrated the importance of combining whole genome CNV and transcriptome analysis in identification of the candidate gene(s) in case studies. We propose the C14orf132 gene expression to be associated with the ELBW-phenotype. C14orf132 gene is a novel long non-coding RNA (lincRNA) with unknown function, which might be associated with the pre- and early postnatal developmental delay through the altered gene expression.
De novo and inherited pathogenic variants in collagen-related osteogenesis imperfecta
(Wiley Periodicals, Inc., 2019) Zhytnik, Lidiia; Maasalu, Katre; Duy, Ho Binh; Pashenko, Andrey; Khmyzov, Sergey; Reimann, Ene; Prans, Ele; Kõks, Sulev; Märtson, Aare
Background: Osteogenesis imperfecta (OI) is a rare genetic bone fragility disorder. In the current study, differences between the genotypes and phenotypes of de novo and inherited collagen‐related OI were investigated. Methods: A comparative analysis was performed of the genotypes and phenotypes of 146 unrelated inherited and de novo collagen I OI cases from Estonia, Ukraine, and Vietnam. Mutational analysis of the subjects and all available parents were per formed with Sanger sequencing. Results: Results showed that 56.16% of the OI cases were caused by de novo patho genic variants. The proportion of OI types OI1, OI4, and OI3 among subjects with inherited OI was 45.31%, 46.88%, and 7.81%, respectively. Among subjects with de novo OI, the proportions of OI types (OI1, OI4, and OI3) were almost equal. Both inherited and de novo OI pathogenic variants occurred more often in the COL1A1 gene than in the COL1A2. The majority of de novo cases were missense pathogenic variants, whereas inherited OI was mostly caused by loss of function pathogenic variants. Conclusion: In summary, there were significant differences between the phenotypes and genotypes of subjects with de novo and inherited OI. These findings may pro mote the further understanding of OI etiology, and assist with diagnostics proce dures, as well as with family plannin
Description of the cytokines and cutaneous neuroendocrine system in the development of vitiligo
(2012-11-02) Reimann, Ene
Vitiliigo on elu jooksul omandatud haigus, kus seni veel täpselt teadmata põhjustel hävinevad melanotsüüdid ja selle tagajärjel tekivad nahale pigmenditud laigud. Patsiendid kannatavad psühholoogilise stressi all ja neil on suurenenud risk saada nahavähk. On teada, et vitiliigohaigetel on muutunud ekspressioonimuster paljudel geenidel, mis osalevad ühe olulisima stressivastuse andja hüpotaalamuse-hüpofüüsi-neerupealise telje (HPA telg) töös. HPA telg koosneb klassikaliselt CRH-POMC-glükokortikoidide signaalirajast ja selle regulatsioonis osalevad erinevad tsütokiinid ja neuromediaatorid. Meie töö eesmärk oli saada lisainformatsiooni närvi- ja immuunsüsteemi interaktsioonidest vitiliigohaigetes. Selleks mõõtsime CRH-POMC-MCH süsteemi, melanogeneesiga seotud tsütokiinide ning dopamiini raja geenide mRNA ja valgu taset vitiliigohaigete ja tervete indiviidide nahas ja veres. Lisaks juba varasemalt näidatud POMC süsteemi geenide (olulised melanogeneesi aktiveerijad) ekspressiooni langusele leidsime, et kasvanud on endogeense opioidi PNOC ja selle retseptori ekspressioon kahjustatud nahas, samuti on suurenenud POMC süsteemi inhibeeriva MCH süsteemi geenide ekspressioon. Näitasime muutusi HPA telje aktiivsust reguleerivate interleukiin-10 perekonna tsütokiinide ja nende retseptorite ekspressioonis ning teiste melanogeneesi ja melanotsüütide kasvu ja arengut reguleerivate tsütokiinide ja muude mediaatorite ekspressioonis. Andsime lisakinnitust neuromediaatori dopamiini raja võimalikule osalusele vitiliigo patogeneesis – lisaks tasakaalu mõjutamisele läbi melanokortiini raja võib dopamiin olukorda nahas ka otseselt muuta. Kokkuvõteks, leidsime, et lokaalse HPA telje funktsioneerimine on vitiliigohaigete nahas oma normaalsest olekust kõrvale kaldunud. Peamiseks põhjuseks näivad olevat muutused melanokortiini rajas, samuti HPA telje tööd aktiveerivate tsütokiinide ja inhibeeriva dopamiini süsteemi muutused võivad tuleneda katsest taastada normaalne olukord ja tasakaal.
Identification of an optimal method for extracting RNA from human skin biopsy, using domestic pig as a model system.
(Nature, 2019-12-27) Reimann, Ene; Kristi, Abram; Kõks, Sulev; Kingo, Külli; Fazeli, Alireza
To evaluate skin tissue gene expression patterns correctly, extracting sufficient quantities of good quality RNA is essential. However, RNA extraction from skin tissue is challenging, as the hyaluronic acid-collagen matrix is extremely difficult to homogenize. Although there are multiple ways to extract RNA from skin, there are no comparative studies that identify the most critical steps, e.g. sample collection, storage and homogenization. We analysed the various steps involved in RNA extraction (i.e. biopsy collection as dry biopsy or into nucleotide stabilizing reagents, different storage conditions, enzymatic digestion, stator-rotor and bead motion-based homogenizing combined with column-based RNA purification). We hypothesised that domestic pig skin is applicable as a model for human skin studies. Altogether twenty different workflows were tested on pig skin and the four most promising workflows were tested on human skin samples. The optimal strategy for extracting human skin RNA was to collect, store and homogenize the sample in RLT lysis buffer from the RNeasy Fibrous Tissue Kit combined with beta-mercaptoethanol. Both stator-rotor and bead motion-based homogenizing were found to result in high quality and quantity of extracted RNA. Our results confirmed that domestic pig skin can be successfully used as a model for human skin RNA studies.
Multicomponent biomarker approach improves the accuracy of diagnostic biomarkers for psoriasis vulgaris
(2019-10-14) Reimann, Ene; Lättekivi, Freddy; Keermann, Maris; Abram, Kristi; Kõks, Sulev; Kingo, Külli; Fazeli, Alireza
Accurate biomarker-based diagnosis of psoriasis vulgaris has remained a challenge; no reliable disease-specific biomarkers have yet been identified. There are several different chronic inflammatory skin diseases that can present similar clinical and dermoscopy features to psoriasis vulgaris, making accurate diagnosis more difficult. Both literature-based and data-driven selection of biomarker was conducted to select candidates for a multicomponent biomarker for psoriasis vulgaris. Support vector machine-based classification models were trained using gene expression data from locally recruited patients and validated on 7 public datasets, which included gene expression data of other inflammatory skin diseases in addition to psoriasis vulgaris. The resulting accuracy of the best classification model based on the expression levels of 4 genes (IL36G, CCL27, NOS2 and C10orf99) was 96.4%, outperforming classification based on other marker gene combinations, which were more affected by variability in gene expression profiles between different datasets and patient groups. This approach has the potential to fill the void of clinically applicable diagnostic biomarkers for psoriasis vulgaris and other inflammatory skin diseases.
Time-critical influences of gestational diet in a seahorse model of male pregnancy
(The Company of Biologists, 2020-02-07) Otero-Ferrer, Francisco; Lättekivi, Freddy; Ord, James; Reimann, Ene; Kõks, Sulev; Izquierdo, Marisol; Holt, William V.; Fazeli, Alireza
Sex role reversal is not uncommon in the animal kingdom but is taken to the extreme by the Syngnathidae, in which male pregnancy is one of the most astonishing idiosyncrasies. However, critical and time-dependent environmental effects on developing embryos, such as those extensively studied in mammalian pregnancy, have not been investigated in the male pregnancy context. Here, we tested the hypothesis that seahorse pregnancy is subject to ‘critical windows’ of environmental sensitivity by feeding male long-snouted seahorses (Hippocampus reidi) a diet deficient in polyunsaturated fatty acids during specific periods before and during pregnancy. Despite embryos being nourished principally by maternally supplied yolk, we found that offspring morphology, fatty acid composition and gene expression profiles were influenced by paternal diet in a manner that depended critically on the timing of manipulation. Specifically, reception of a diet deficient in polyunsaturated fatty acids in the days preceding pregnancy resulted in smaller newborn offspring, while the same diet administered towards the end of pregnancy resulted in substantial alterations to newborn gene expression and elongation of the snout at 10 days old. Although paternal diet did not affect 10 day survival, the observed morphological alterations in some cases could have important fitness consequences in the face of natural selective pressures such as predation and food availability. Our results demonstrate that, under male pregnancy, fine-scale temporal variation in parental diet quality and subsequent critical window effects should not be overlooked as determinants of developing offspring fitness.