Publications by authors named "Tomasz Grzybowski"

88 Publications

Searching for improvements in predicting human eye colour from DNA.

Int J Legal Med 2021 Jul 14. Epub 2021 Jul 14.

Malopolska Centre of Biotechnology of the Jagiellonian University, Kraków, Poland.

Increasing understanding of human genome variability allows for better use of the predictive potential of DNA. An obvious direct application is the prediction of the physical phenotypes. Significant success has been achieved, especially in predicting pigmentation characteristics, but the inference of some phenotypes is still challenging. In search of further improvements in predicting human eye colour, we conducted whole-exome (enriched in regulome) sequencing of 150 Polish samples to discover new markers. For this, we adopted quantitative characterization of eye colour phenotypes using high-resolution photographic images of the iris in combination with DIAT software analysis. An independent set of 849 samples was used for subsequent predictive modelling. Newly identified candidates and 114 additional literature-based selected SNPs, previously associated with pigmentation, and advanced machine learning algorithms were used. Whole-exome sequencing analysis found 27 previously unreported candidate SNP markers for eye colour. The highest overall prediction accuracies were achieved with LASSO-regularized and BIC-based selected regression models. A new candidate variant, rs2253104, located in the ARFIP2 gene and identified with the HyperLasso method, revealed predictive potential and was included in the best-performing regression models. Advanced machine learning approaches showed a significant increase in sensitivity of intermediate eye colour prediction (up to 39%) compared to 0% obtained for the original IrisPlex model. We identified a new potential predictor of eye colour and evaluated several widely used advanced machine learning algorithms in predictive analysis of this trait. Our results provide useful hints for developing future predictive models for eye colour in forensic and anthropological studies.
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http://dx.doi.org/10.1007/s00414-021-02645-5DOI Listing
July 2021

A Combined Analysis of Gut and Skin Microbiota in Infants with Food Allergy and Atopic Dermatitis: A Pilot Study.

Nutrients 2021 May 15;13(5). Epub 2021 May 15.

Department of Pediatrics, Allergology and Gastroenterology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 87-100 Toruń, Poland.

The gut microbiota in patients with food allergy, and the skin microbiota in atopic dermatitis patients differ from those of healthy people. We hypothesize that relationships may exist between gut and skin microbiota in patients with allergies. The aim of this study was to determine the possible relationship between gut and skin microbiota in patients with allergies, hence simultaneous analysis of the two compartments of microbiota was performed in infants with and without allergic symptoms. Fifty-nine infants with food allergy and/or atopic dermatitis and 28 healthy children were enrolled in the study. The skin and gut microbiota were evaluated using 16S rRNA gene amplicon sequencing. No significant differences in the α-diversity of dermal or fecal microbiota were observed between allergic and non-allergic infants; however, a significant relationship was found between bacterial community structure and allergy phenotypes, especially in the fecal samples. Certain clinical conditions were associated with characteristic bacterial taxa in the skin and gut microbiota. Positive correlations were found between skin and fecal samples in the abundance of among allergic infants, and and among healthy infants. Although infants with allergies and healthy infants demonstrate microbiota with similar α-diversity, some differences in β-diversity and bacterial species abundance can be seen, which may depend on the phenotype of the allergy. For some organisms, their abundance in skin and feces samples may be correlated, and these correlations might serve as indicators of the host's allergic state.
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http://dx.doi.org/10.3390/nu13051682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156695PMC
May 2021

Clear phylogeographic pattern and genetic structure of wild boar Sus scrofa population in Central and Eastern Europe.

Sci Rep 2021 May 6;11(1):9680. Epub 2021 May 6.

Department of Forensic Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland.

The wild boar Sus scrofa is one of the widely spread ungulate species in Europe, yet the origin and genetic structure of the population inhabiting Central and Eastern Europe are not well recognized. We analysed 101 newly obtained sequences of complete mtDNA genomes and 548 D-loop sequences of the species and combined them with previously published data. We identified five phylogenetic clades in Europe with clear phylogeographic pattern. Two of them occurred mainly in western and central part of the continent, while the range of the third clade covered North-Eastern, Central and South-Eastern Europe. The two other clades had rather restricted distribution. In Central Europe, we identified a contact zone of three mtDNA clades. Population genetic structure reflected clear phylogeographic pattern of wild boar in this part of Europe. The contribution of lineages originating from the southern (Dinaric-Balkan) and eastern (northern cost of the Black Sea) areas to the observed phylogeographic pattern of the species in Central and Eastern Europe was larger than those from the regions located in southern France, Iberian, and Italian Peninsulas. The present work was the first mitogenomic analysis conducted in Central and Eastern Europe to study genetic diversity and structure of wild boar population.
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http://dx.doi.org/10.1038/s41598-021-88991-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102581PMC
May 2021

The microbiome and its impact on food allergy and atopic dermatitis in children.

Postepy Dermatol Alergol 2020 Oct 7;37(5):641-650. Epub 2020 Nov 7.

Department of Paediatrics, Allergology and Gastroenterology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland.

Food allergy (FA) affects 4-10% of children, especially children with atopic dermatitis (AD). During infancy the gut microbiome may determine both the course of FA and tolerance to food allergens. Analogically, the skin microbiome changes in the course of AD. Most studies have associated FA with a lower abundance and diversity of Lactobacillales and Clostridiales, but greater numbers of Enterobacterales, while AD in children has been associated with lower numbers of and but an abundance of and . An understanding of the impact of the microbiome on the clinical course of FA and AD may allow for the development of new models of allergy treatment and prevention.
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http://dx.doi.org/10.5114/ada.2019.90120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675070PMC
October 2020

Recommendations of the Polish Speaking Working Group of the International Society for Forensic Genetics on forensic Y chromosome typing.

Arch Med Sadowej Kryminol 2020 ;70(1):1-18

Pracownia Genetyki Medycznej i Sądowej, Uniwersytet Medyczny w Łodzi, Polska.

Y chromosome typing has been performed in forensic genetic practice for more than 20 years. The latest recommendations of the DNA Commission of the International Society of Forensic Genetics (ISFG) concerning the application of Y-chromosomal markers in forensic genetics were published in 2006. The aim of this report is to recapitulate, systematise and supplement existing recommendations on the forensic analysis of polymorphism of the Y chromosome with standards already implemented in practice, new capabilities linked to the development of research techniques as well as current solutions used in statistical analysis. The recommendations have been adapted specifically to aspects related to the preparation of expert opinions in the field of forensic genetics in Poland. The Polish Speaking Working Group of the ISFG believes that the presented guidelines should become a standard implemented by all Polish laboratories performing Y chromosome typing for forensic purposes.
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http://dx.doi.org/10.5114/amsik.2020.97833DOI Listing
January 2020

Exploring the possibility of predicting human head hair greying from DNA using whole-exome and targeted NGS data.

BMC Genomics 2020 Aug 5;21(1):538. Epub 2020 Aug 5.

Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.

Background: Greying of the hair is an obvious sign of human aging. In addition to age, sex- and ancestry-specific patterns of hair greying are also observed and the progression of greying may be affected by environmental factors. However, little is known about the genetic control of this process. This study aimed to assess the potential of genetic data to predict hair greying in a population of nearly 1000 individuals from Poland.

Results: The study involved whole-exome sequencing followed by targeted analysis of 378 exome-wide and literature-based selected SNPs. For the selection of predictors, the minimum redundancy maximum relevance (mRMRe) method was used, and then two prediction models were developed. The models included age, sex and 13 unique SNPs. Two SNPs of the highest mRMRe score included whole-exome identified KIF1A rs59733750 and previously linked with hair loss FGF5 rs7680591. The model for greying vs. no greying prediction achieved accuracy of cross-validated AUC = 0.873. In the 3-grade classification cross-validated AUC equalled 0.864 for no greying, 0.791 for mild greying and 0.875 for severe greying. Although these values present fairly accurate prediction, most of the prediction information was brought by age alone. Genetic variants explained < 10% of hair greying variation and the impact of particular SNPs on prediction accuracy was found to be small.

Conclusions: The rate of changes in human progressive traits shows inter-individual variation, therefore they are perceived as biomarkers of the biological age of the organism. The knowledge on the mechanisms underlying phenotypic aging can be of special interest to the medicine, cosmetics industry and forensics. Our study improves the knowledge on the genetics underlying hair greying processes, presents prototype models for prediction and proves hair greying being genetically a very complex trait. Finally, we propose a four-step approach based on genetic and epigenetic data analysis allowing for i) sex determination; ii) genetic ancestry inference; iii) greying-associated SNPs assignment and iv) epigenetic age estimation, all needed for a final prediction of greying.
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http://dx.doi.org/10.1186/s12864-020-06926-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430834PMC
August 2020

Complete mitogenome data for the Serbian population: the contribution to high-quality forensic databases.

Int J Legal Med 2020 Sep 6;134(5):1581-1590. Epub 2020 Jun 6.

Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, PO Box 23, Vojvode Stepe 444a, Belgrade, 11010, Serbia.

Mitochondrial genome (mtDNA) is a valuable resource in resolving various human forensic casework. The usage of variability of complete mtDNA genomes increases their discriminatory power to the maximum and enables ultimate resolution of distinct maternal lineages. However, their wider employment in forensic casework is nowadays limited by the lack of appropriate reference database. In order to fill in the gap in the reference data, which, considering Slavic-speaking populations, currently comprises only mitogenomes of East and West Slavs, we present mitogenome data for 226 Serbians, representatives of South Slavs from the Balkan Peninsula. We found 143 (sub)haplogroups among which West Eurasian ones were dominant. The percentage of unique haplotypes was 85%, and the random match probability was as low as 0.53%. We support previous findings on both high levels of genetic diversity in the Serbian population and patterns of genetic differentiation among this and ten studied European populations. However, our high-resolution data supported more pronounced genetic differentiation among Serbians and two Slavic populations (Russians and Poles) as well as expansion of the Serbian population after the Last Glacial Maximum and during the Migration period (fourth to ninth century A.D.), as inferred from the Bayesian skyline analysis. Phylogenetic analysis of haplotypes found in Serbians contributed towards the improvement of the worldwide mtDNA phylogeny, which is essential for the interpretation of the mtDNA casework.
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http://dx.doi.org/10.1007/s00414-020-02324-xDOI Listing
September 2020

Examination of LT-DNA traces - literature overview and general recommendations of the Polish Speaking Working Group of the International Society for Forensic Genetics (ISFG-PL).

Arch Med Sadowej Kryminol 2020 ;70(2-3):103-123

Uniwersytet Medyczny w Łodzi, Polska.

The available literature on traces characterised by a suboptimal amount of DNA, as well as expert research practice, show the complex nature of LT-DNA traces: from their detection and collection, through genetic analysis, up to the interpretation of final results. The aims of this paper are to systematise the current state of knowledge on handling LT-DNA traces and develop examination guidelines, as recommended by the Polish Speaking Working Group of the International Society for Forensic Genetics (ISFG-PL). The proposed guidelines should be followed by all Polish laboratories conducting forensic genetic analyses for the purpose of judicial proceedings.
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http://dx.doi.org/10.5114/amsik.2020.104489DOI Listing
January 2020

DNA-based predictive models for the presence of freckles.

Forensic Sci Int Genet 2019 09 30;42:252-259. Epub 2019 Jul 30.

Malopolska Centre of Biotechnology of the Jagiellonian University, Gronostajowa St. 7A, 30-387 Kraków, Poland; Central Forensic Laboratory of the Police, Aleje Ujazdowskie 7, 00-583 Warszawa, Poland. Electronic address:

Freckles or ephelides are hyperpigmented spots observed on skin surface mainly in European and Asian populations. Easy recognition and external visibility make prediction of ephelides, the potentially useful target in the field of forensic DNA phenotyping. Prediction of freckles would be a step forward in sketching the physical appearance of unknown perpetrators or decomposed cadavers for the forensic DNA intelligence purposes. Freckles are especially common in people with pale skin and red hair and therefore it is expected that predisposition to freckles may partially share the genetic background with other pigmentation traits. The first proposed freckle prediction model was developed based on investigation that involved variation of MC1R and 8 SNPs from 7 genes in a Spanish cohort [19]. In this study we examined 113 DNA variants from 46 genes previously associated with human pigmentation traits and assessed their impact on freckles presence in a group of 960 individuals from Poland. Nineteen DNA variants revealed associations with the freckle phenotype and the study also revealed that females have ∼1.8 higher odds of freckles presence comparing to males (p-value = 9.5 × 10). Two alternative prediction models were developed using regression methods. A simplified binomial 12-variable model predicts the presence of ephelides with cross-validated AUC = 0.752. A multinomial 14-variable model predicts one of three categories - non-freckled, medium freckled and heavily freckled. The two extreme categories, non-freckled and heavily freckled were predicted with moderately high accuracy of cross-validated AUC = 0.754 and 0.792, respectively. Prediction accuracy of the intermediate category was lower, AUC = 0.657. The study presents novel DNA models for prediction of freckles that can be used in forensic investigations and emphasizes significance of pigmentation genes and sex in predictive DNA analysis of freckles.
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http://dx.doi.org/10.1016/j.fsigen.2019.07.012DOI Listing
September 2019

Polymorphisms in Patients with Pseudoexfoliation Syndrome in Polish Population.

J Ophthalmol 2019 1;2019:8787149. Epub 2019 Jul 1.

Department of Ophthalmology, The Nicolaus Copernicus University, Ludwik Rydygier's Collegium Medicum in Bydgoszcz, Skłodowskiej Curie 9, 85-094 Bydgoszcz, Poland.

Purpose: To evaluate polymorphisms in patients with pseudoexfoliation syndrome.

Materials And Methods: We studied 81 patients (23 males and 58 females, the median age 76 years) and 91 control subjects (27 males and 64 females, the median age 75 years). Genotypes of the polymorphisms (SNPs), rs3087554 and rs2279590, were determined using a commercially available validated genotyping assays. The test was performed to compare patient and control groups for possible associations between SNP genotype/allele frequency and disease state.

Results: There were no significant differences for both allele and genotype frequencies between PEX patients and controls for rs3087554 and rs2279590 polymorphisms. The haplotypes distribution shows statistically significant difference between groups (=0.03). The haplotype (CT) more often was found in controls than in PEX patients, conferring an 18-fold decreased risk to the disease.

Conclusion: Our results indicate that CLU variants may contribute to the risk of PEX in the Polish population.
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http://dx.doi.org/10.1155/2019/8787149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636577PMC
July 2019

Mitogenome germline mutations and colorectal cancer risk in Polish population.

Arch Med Sci 2020 16;16(2):366-373. Epub 2019 Jan 16.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Introduction: To date, several nuclear DNA variants have been shown to be associated with increased risk of developing colorectal cancer. Despite the fact that mitochondria play an important role in carcinogenesis, little is known about inherited mitochondrial DNA mutations that could be involved in this disease. Thus, potential associations between inherited mutations in the entire mitochondrial genomes and colorectal cancer were analysed in this study.

Material And Methods: Two hundred mitogenome sequences determined for colorectal cancer patients and healthy individuals from Poland were used to investigate the association between mtDNA alleles or haplogroups and colorectal cancer. Additional mtDNA control region haplotypes determined for 1353 individuals from the general Polish population were used for comparison of haplogroup and certain allele frequencies between case and control groups.

Results: The non-R clades together with their diagnostic T alleles at positions 12705 and 16223 were observed with higher frequencies in healthy individuals than in colorectal cancer patients. Nevertheless, the differences of the R macrohaplogroup (as well as 12705 or 16223 alleles) frequencies between cases and controls were statistically insignificant after Bonferroni correction. Most of the non-R clades were of Asian and African origin, but none of them were prevalent in the control group. Moreover, neither mtDNA alleles nor haplogroups were associated with clinicopathological parameters of colorectal cancer patients.

Conclusions: Contrary to some previous reports, the findings of this study do not support the hypothesis that mitochondrial DNA variants contribute to inherited predisposition to colorectal cancer.
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http://dx.doi.org/10.5114/aoms.2018.80893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069428PMC
January 2019

TP53 somatic mutations are associated with somatic mitogenome substitutions but not indels in colorectal cancer cells.

J Gene Med 2019 01 7;21(1):e3063. Epub 2019 Jan 7.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Background: p53 is a tumour suppressor protein that is involved in many cancer-related processes. Growing evidence suggests that p53 also plays an important role in mitochondrial (mtDNA) maintenance. Somatic mitogenome mutations are frequently observed in colorectal cancer (CC) cells. Thus, it was important to determine whether somatic mtDNA changes are associated with TP53 mutational status.

Methods: In the present study, we analysed the TP53 gene in 67 CC patients, for whom mitogenome haplotypes were previously described. In total, 134 TP53 sequences (of cancer and matched normal specimens) were determined using the dideoxy method.

Results: Nine hereditary polymorphisms in the TP53 gene were detected in normal colon cells. None of them (neither alleles, nor genotypes) was associated with somatic mitogenome mutations in CC cells. Moreover, 42 somatic TP53 mutations were found in approximately 36% of CC tissues. These somatic changes were significantly more frequent in CC cells with somatic mtDNA mutations (p = 0.0069). Furthermore, we show that only mitochondrial somatic substitutions (p = 0.0017), but not indels (p > 0.05), were associated with somatic TP53 mutations.

Conclusions: The results of the present study suggest that changes in TP53 may modify p53 properties, which may result in the accumulation of somatic substitutions in CC mitogenomes.
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http://dx.doi.org/10.1002/jgm.3063DOI Listing
January 2019

An Analysis of the Association between Epilepsy-Related Genes and Vertigo in the Polish Population.

Audiol Neurootol 2018 9;23(3):135-144. Epub 2018 Oct 9.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz,

Considering the possibility of a common genetic background of vertigo and epilepsy, we genotyped an affected group of individuals with vertigo and an unaffected group, by studying 26 single-nucleotide polymorphisms (SNPs) in 14 genes which were previously reported to be of particular importance for epilepsy. Significant differences were found between the patients and the control group (χ2 = 38.3, df = 3, p = 1.6 × 10-7) for the frequencies of haplotypes consist ing of 2 SNPs located in chromosome 11 (rs1939012 and rs1783901 within genes MMP8 and SCN3B, respectively). The haplotype rs1939012:C-rs1783901:A, consisting of the minor-frequency alleles was found to be associated with a higher risk of vertigo (OR = 5.0143, 95% CI = 1.6991-14.7980, p = 0.0035). In contrast, the haplotype rs1939012:T-rs1783901:A showed a significant association with a decreased risk of the disease (OR = 0.0597, 95% CI = 0.0136-0.2620, p = 0.0002). Our results suggest that the SNPs rs1939012 and rs1783901 may play a potential role of gene regulation and/or epistasis in a complex etiology of vertigo.
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http://dx.doi.org/10.1159/000491992DOI Listing
October 2019

Whole mitochondrial genome diversity in two Hungarian populations.

Mol Genet Genomics 2018 Oct 9;293(5):1255-1263. Epub 2018 Jun 9.

Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, 1085, Hungary.

Complete mitochondrial genomics is an effective tool for studying the demographic history of human populations, but there is still a deficit of mitogenomic data in European populations. In this paper, we present results of study of variability of 80 complete mitochondrial genomes in two Hungarian populations from eastern part of Hungary (Szeged and Debrecen areas). The genetic diversity of Hungarian mitogenomes is remarkably high, reaching 99.9% in a combined sample. According to the analysis of molecular variance (AMOVA), European populations showed a low, but statistically significant level of between-population differentiation (Fst = 0.61%, p = 0), and two Hungarian populations demonstrate lack of between-population differences. Phylogeographic analysis allowed us to identify 71 different mtDNA sub-clades in Hungarians, sixteen of which are novel. Analysis of ancestry-informative mtDNA sub-clades revealed a complex genetic structure associated with the genetic impact of populations from different parts of Eurasia, though the contribution from European populations is the most pronounced. At least 8% of ancestry-informative haplotypes found in Hungarians demonstrate similarity with East and West Slavic populations (sub-clades H1c23a, H2a1c1, J2b1a6, T2b25a1, U4a2e, K1c1j, and I1a1c), while the influence of Siberian populations is not so noticeable (sub-clades A12a, C4a1a, and probably U4b1a4).
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http://dx.doi.org/10.1007/s00438-018-1458-xDOI Listing
October 2018

Evaluation of TGF-Beta 2 and VEGF Gene Expression Levels in Epiretinal Membranes and Internal Limiting Membranes in the Course of Retinal Detachments, Proliferative Diabetic Retinopathy, Macular Holes, and Idiopathic Epiretinal Membranes.

J Ophthalmol 2018 23;2018:8293452. Epub 2018 Apr 23.

Department of Ophthalmology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.

Purpose: To evaluate the expression profiles of the VEGF and TGF in the ERMs and ILMs in retinal disorders.

Methods: In this nonrandomized prospective study, 75 patients (34 females and 41 males) referred to pars plana vitrectomy (PPV) due to different retinal diseases were enrolled to the study. The samples of ERMs and ILMs collected during PPV were immediately put in TRIzol® Reagent (Life Technologies, USA) and stored at -70°C until RNA extraction. Gene expression analysis was done with TaqMan® Gene Expression Assays (Applied Biosystems, USA) following the manufacturer's instructions.

Results: The gene expression levels of VEGF as well as of TGF2 were significantly higher in ERMs than in ILMs in all studied groups. The level of TGF2 expression exhibits a significantly lower values in iERMs as compared with the RRD group ( = 0.043). There were differences in TGF2 expression in ILM in groups studied: DR versus RRD, = 0.003; DR versus iERM, = 0,047; and iERM versus RRD, = 0.004.

Conclusions: Our results revealed that factors associated with angiogenesis and wound healing processes in eyes with RRD, PDR, iERM, and MH were more upregulated in ERMs than in ILMs. This may indicate that ILM is not responsible for reproliferation and its peeling should be avoided in routine PPV.
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http://dx.doi.org/10.1155/2018/8293452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937441PMC
April 2018

X-linked TLR7 gene polymorphisms are associated with diverse immunological conditions but not with discoid lupus erythematosus in Polish patients.

Postepy Dermatol Alergol 2018 Feb 20;35(1):26-32. Epub 2018 Feb 20.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland.

Introduction: Toll-like receptor 7 (TLR7) is an important molecule involved in the development of autoimmunity and the response to different pathogens. Several polymorphisms within the gene were previously found to be associated with systemic lupus erythematosus (SLE). However, none of those studies investigated the promoter flanking variants rs1634318 and rs1616583. gene diversity has not been analyzed with respect to discoid lupus erythematosus (DLE) development, while its role in the human immunological response to fungal infection is not fully known.

Aim: To clarify the potential involvement of two novel single-nucleotide polymorphisms (SNPs) located in the gene (rs1634318 and rs1616583) in a variety of immune-related conditions, we studied the variability of these loci in patients from a Polish population with SLE and DLE, as well as in immunocompromised patients who were affected by invasive aspergillosis (IA) and those who were not affected.

Material And Methods: Real-time polymerase chain reaction was used to genotype SNPs. Statistically significant differences between case and control groups for both allele and genotype frequencies were assessed using the χ test with Yates' correction or two-tailed Fisher's exact test. The results were Bonferroni-corrected for multiple comparisons and odds ratios were calculated.

Results: Two polymorphisms located in might be associated with the development of SLE but not DLE within the Polish population. Moreover, variation of the two investigated SNPs was found to be associated with IA in immunocompromised Polish patients.

Conclusions: In Polish patients, promoter flanking gene polymorphisms might be associated with IA and SLE but not DLE.
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http://dx.doi.org/10.5114/pdia.2017.69984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872239PMC
February 2018

Massively parallel targeted resequencing reveals novel genetic variants associated with aspergillosis in paediatric patients with haematological malignancies.

Pol J Pathol 2017;68(3):210-217

This study aimed to find novel genetic variants of susceptibility to aspąergillosis in paediatric patients with haematological malignancies. Complete sequences of fifteen genes of human innate immunity (CCL2, CCR2, CD209, CLEC6A, CLEC7A and ten TLR genes) were studied in 40 patients diagnosed with haematological disorders (20 unaffected and 20 affected by aspergillosis). All samples were sequenced with MiSeq (Illumina) and 454 (Roche Diagnostics) technologies. Statistical significance of the differences between studied groups was determined using the two-tailed Fisher's exact test. Sixty variants of potential importance were identified, the vast majority of which are located in non-coding parts of the targeted genes. At the threshold of p < 0.000005, one intergenic (TLR2 rs4585282) and one intronic variant (CLEC6A rs12099687) were found significant between the case and control groups for genotype and allele frequencies, respectively. Rs12099687 in CLEC6A was predicted to constitute an alternative isoform or cryptic splice site, which potentially changes activity of the Dectin-2 protein. Overall, we assume that the two strongest associations reported in this study are expected to be reproducible even in the absence of other evidence, while another twelve associations may be strong enough to justify additional research in larger cohorts.
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http://dx.doi.org/10.5114/pjp.2017.71528DOI Listing
March 2018

Mitogenomic differences between the normal and tumor cells of colorectal cancer patients.

Hum Mutat 2018 05 24;39(5):691-701. Epub 2018 Jan 24.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.

So far, a reliable spectrum of mitochondrial DNA mutations in colorectal cancer cells is still unknown, and neither is their significance in carcinogenesis. Indeed, it remains debatable whether mtDNA mutations are "drivers" or "passengers" of colorectal carcinogenesis. Thus, we analyzed 200 mitogenomes from normal and cancer tissues of 100 colorectal cancer patients. Minority variant mutations were detected at the 1% level. We showed that somatic mutations frequently occur in colorectal cancer cells (75%) and are randomly distributed across the mitochondrial genome. Mutational signatures of somatic mitogenome mutations suggest that they might arise through nucleotide deamination due to oxidative stress. The majority of somatic mutations localized within the coding region (in positions not known from the human phylogeny) and was potentially pathogenic to cell metabolism. Further analysis suggested that the relaxation of negative selection in the mitogenomes of colorectal cancer cells may allow accumulation of somatic mutations. Thus, a shift in glucose metabolism from oxidative phosphorylation to glycolysis may create advantageous conditions for accumulation of mtDNA mutations. Considering the fact that the presence of somatic mtDNA mutations was not associated with any clinicopathological features, we suggested that mtDNA somatic mutations are "passengers" rather than the cause of colorectal carcinogenesis.
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http://dx.doi.org/10.1002/humu.23402DOI Listing
May 2018

Recommendations of the Polish Speaking Working Group of the International Society for Forensic Genetics for forensic mitochondrial DNA testing.

Arch Med Sadowej Kryminol 2018 ;68(4):242-258

Although mitochondrial DNA (mtDNA) testing has been used in forensic genetics only since the mid-1990s, forensic DNA laboratories have been recently increasing the range of mtDNA sequencing, employing new analytical approaches and methods of data analysis. Therefore, it seems fitting to gather and systematize existing recommendations in the field of mtDNA analysis for forensic purposes, and formulate a set of interpretative guidelines which are especially relevant in view of recent developments in the forensic casework. The starting point is the recommendations of the International Society for Forensic Genetics (ISFG) which, in the opinion of the Polish Speaking Working Group of the ISFG (ISFG- PL), should be followed by all Polish laboratories conducting forensic testing.
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http://dx.doi.org/10.5114/amsik.2018.84532DOI Listing
September 2019

The Association of Apolipoprotein E Gene Polymorphism With Cognitive Performance in Nondemented Polish Adults Aged 55 to 75.

Int J Aging Hum Dev 2018 09 28;87(2):124-140. Epub 2017 Aug 28.

1 Collegium Medicum, 49604 Uniwersytet Mikolaja Kopernika , Bydgoszcz, Poland.

The ε4 allele of the apolipoprotein E (APOE) gene is known as a risk factor for dementia. How APOE ε polymorphism affects cognitive performance in nondemented aging subjects remains less clear. In this study, the relationship between APOE status and cognitive performance across various cognitive domains in adults aged 55 to 75 years ( n = 74) without dementia was investigated. E4 carriers ( n = 11) performed worse versus noncarriers on forward Digit Span and delayed recall of the Rey-Osterrieth complex figure. General linear model analysis revealed a small but significant main effect of ε4 on Rey-Osterrieth complex figure delayed recall. Comparing ε2 carriers, ε3 homozygotes, and ε4 carriers, ε3/ε3 performed significantly better on Trail Making Test part B and derived score Trail Making Test B-A. The findings support the relation between the APOE ε polymorphism and visual memory, short-term auditory memory, visuospatial attention, and executive functions in an aging sample without dementia.
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http://dx.doi.org/10.1177/0091415017724548DOI Listing
September 2018

Genetic similarities and differences between discoid and systemic lupus erythematosus patients within the Polish population.

Postepy Dermatol Alergol 2017 Jun 29;34(3):228-232. Epub 2017 May 29.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland.

Introduction: Many studies have shown that some SNPs might be a risk factor for systemic lupus erythematosus (SLE), but little is known about potential susceptibility loci of the skin types of the disease. Discoid lupus erythematosus (DLE) is the most common form of the cutaneous lupus erythematosus. Nevertheless, a genetic contribution to DLE is not fully recognized.

Aim: We aimed to analyze three SNPs located in the (rs7574865), (rs1143679) and (rs1150754) genes in both DLE and SLE patients from Poland.

Material And Methods: SNPs were genotyped using real-time polymerase chain reaction (PCR). Statistical significance of the differences between patient and control groups in both allele and genotype frequencies were calculated using two tailed Fisher's exact test. The correction for multiple testing by the Bonferroni adjustment and odds ratio were also calculated.

Results: For the first time, we have shown that the polymorphisms located in the (rs7574865), but not in the (rs1143679) nor the (rs1150754) genes, might be associated with the development of DLE within the Polish population. The variation of the three investigated SNPs was found to be associated with SLE in our dataset.

Conclusions: The results of our study suggest differences in the molecular background between DLE and SLE within the Polish population.
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http://dx.doi.org/10.5114/pdia.2017.67479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471372PMC
June 2017

Mitogenomic diversity in Russians and Poles.

Forensic Sci Int Genet 2017 09 15;30:51-56. Epub 2017 Jun 15.

N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences,Gubkin Street 3, Moscow 119991, Russia, Russia.

Complete mtDNA genome sequencing improves molecular resolution for distinguishing variation between individuals and populations, but there is still deficiency of mitogenomic population data. To overcome this limitation, we used Sanger-based protocol to generate complete mtDNA sequences of 376 Russian individuals from six populations of European part of Russia and 100 Polish individuals from northern Poland. Nearly complete resolution of mtDNA haplotypes was achieved - about 97% of haplotypes were unique both in Russians and Poles, and no haplotypes overlapped between them when indels were considered. While European populations showed a low, but statistically significant level of between-population differentiation (Fst=0.66%, p=0), Russians demonstrate lack of between-population differences (Fst=0.22%, p=0.15). Results of the Bayesian skyline analysis of Russian mitogenomes demonstrate not only post-Last Glacial Maximum expansion, but also rapid population growth starting from about 4.3kya (95% CI: 2.9-5.8kya), i.e. in the Bronze Age. This expansion strongly correlates with the Kurgan model established by archaeologists and confirmed by paleogeneticists.
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http://dx.doi.org/10.1016/j.fsigen.2017.06.003DOI Listing
September 2017

Intra- and inter-population analysis of haplotype diversity in Yfiler Plus system using a wide set of representative data from Polish population.

Forensic Sci Int Genet 2017 05 27;28:e22-e25. Epub 2017 Jan 27.

Central Forensic Laboratory of the Police, Warsaw, Poland; Department of Forensic Medicine, Warsaw Medical University, Warsaw, Poland; Department of Forensic Medicine, Institute of Molecular and Forensic Genetics, Collegium Medicum of the Nicolaus Copernicus University, Bydgoszcz, Poland. Electronic address:

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http://dx.doi.org/10.1016/j.fsigen.2017.01.014DOI Listing
May 2017

Mitochondrial super-haplogroup U diversity in Serbians.

Ann Hum Biol 2017 Aug 19;44(5):408-418. Epub 2017 Feb 19.

a Institute of Molecular Genetics and Genetic Engineering , University of Belgrade , Belgrade , Serbia.

Background: Available mitochondrial (mtDNA) data demonstrate genetic differentiation among South Slavs inhabiting the Balkan Peninsula. However, their resolution is insufficient to elucidate the female-specific aspects of the genetic history of South Slavs, including the genetic impact of various migrations which were rather common within the Balkans, a region having a turbulent demographic history.

Aim: The aim was to thoroughly study complete mitogenomes of Serbians, a population linking westward and eastward South Slavs.

Subjects And Methods: Forty-six predominantly Serbian super-haplogroup U complete mitogenomes were analysed phylogenetically against ∼4000 available complete mtDNAs of modern and ancient Western Eurasians.

Results: Serbians share a number of U mtDNA lineages with Southern, Eastern-Central and North-Western Europeans. Putative Balkan-specific lineages (e.g. U1a1c2, U4c1b1, U5b3j, K1a4l and K1a13a1) and lineages shared among Serbians (South Slavs) and West and East Slavs were detected (e.g. U2e1b1, U2e2a1d, U4a2a, U4a2c, U4a2g1, U4d2b and U5b1a1).

Conclusion: The exceptional diversity of maternal lineages found in Serbians may be associated with the genetic impact of both autochthonous pre-Slavic Balkan populations whose mtDNA gene pool was affected by migrations of various populations over time (e.g. Bronze Age pastoralists) and Slavic and Germanic newcomers in the early Middle Ages.
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http://dx.doi.org/10.1080/03014460.2017.1287954DOI Listing
August 2017

Single Nucleotide Polymorphism Discovery in Bovine Pituitary Gland Using RNA-Seq Technology.

PLoS One 2016 8;11(9):e0161370. Epub 2016 Sep 8.

Waksman Institute of Microbiology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.

Examination of bovine pituitary gland transcriptome by strand-specific RNA-seq allows detection of putative single nucleotide polymorphisms (SNPs) within potential candidate genes (CGs) or QTLs regions as well as to understand the genomics variations that contribute to economic trait. Here we report a breed-specific model to successfully perform the detection of SNPs in the pituitary gland of young growing bulls representing Polish Holstein-Friesian (HF), Polish Red, and Hereford breeds at three developmental ages viz., six months, nine months, and twelve months. A total of 18 bovine pituitary gland polyA transcriptome libraries were prepared and sequenced using the Illumina NextSeq 500 platform. Sequenced FastQ databases of all 18 young bulls were submitted to NCBI-SRA database with NCBI-SRA accession numbers SRS1296732. For the investigated young bulls, a total of 113,882,3098 raw paired-end reads with a length of 156 bases were obtained, resulting in an approximately 63 million paired-end reads per library. Breed-wise, a total of 515.38, 215.39, and 408.04 million paired-end reads were obtained for Polish HF, Polish Red, and Hereford breeds, respectively. Burrows-Wheeler Aligner (BWA) read alignments showed 93.04%, 94.39%, and 83.46% of the mapped sequencing reads were properly paired to the Polish HF, Polish Red, and Hereford breeds, respectively. Constructed breed-specific SNP-db of three cattle breeds yielded at 13,775,885 SNPs. On an average 765,326 breed-specific SNPs per young bull were identified. Using two stringent filtering parameters, i.e., a minimum 10 SNP reads per base with an accuracy ≥ 90% and a minimum 10 SNP reads per base with an accuracy = 100%, SNP-db records were trimmed to construct a highly reliable SNP-db. This resulted in a reduction of 95,7% and 96,4% cut-off mark of constructed raw SNP-db. Finally, SNP discoveries using RNA-Seq data were validated by KASP™ SNP genotyping assay. The comprehensive QTLs/CGs analysis of 76 QTLs/CGs with RNA-seq data identified KCNIP4, CCSER1, DPP6, MAP3K5 and GHR CGs with highest SNPs hit loci in all three breeds and developmental ages. However, CAST CG with more than 100 SNPs hits were observed only in Polish HF and Hereford breeds.These findings are important for identification and construction of novel tissue specific SNP-db and breed specific SNP-db dataset by screening of putative SNPs according to QTL db and candidate genes for bovine growth and reproduction traits, one can develop genomic selection strategies for growth and reproductive traits.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161370PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015895PMC
August 2017

Diversifying Selection Between Pure-Breed and Free-Breeding Dogs Inferred from Genome-Wide SNP Analysis.

G3 (Bethesda) 2016 08 9;6(8):2285-98. Epub 2016 Aug 9.

Museum and Institute of Zoology, Polish Academy of Sciences, 00-679 Warszawa, Poland

Domesticated species are often composed of distinct populations differing in the character and strength of artificial and natural selection pressures, providing a valuable model to study adaptation. In contrast to pure-breed dogs that constitute artificially maintained inbred lines, free-ranging dogs are typically free-breeding, i.e., unrestrained in mate choice. Many traits in free-breeding dogs (FBDs) may be under similar natural and sexual selection conditions to wild canids, while relaxation of sexual selection is expected in pure-breed dogs. We used a Bayesian approach with strict false-positive control criteria to identify FST-outlier SNPs between FBDs and either European or East Asian breeds, based on 167,989 autosomal SNPs. By identifying outlier SNPs located within coding genes, we found four candidate genes under diversifying selection shared by these two comparisons. Three of them are associated with the Hedgehog (HH) signaling pathway regulating vertebrate morphogenesis. A comparison between FBDs and East Asian breeds also revealed diversifying selection on the BBS6 gene, which was earlier shown to cause snout shortening and dental crowding via disrupted HH signaling. Our results suggest that relaxation of natural and sexual selection in pure-breed dogs as opposed to FBDs could have led to mild changes in regulation of the HH signaling pathway. HH inhibits adhesion and the migration of neural crest cells from the neural tube, and minor deficits of these cells during embryonic development have been proposed as the underlying cause of "domestication syndrome." This suggests that the process of breed formation involved the same genetic and developmental pathways as the process of domestication.
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http://dx.doi.org/10.1534/g3.116.029678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978884PMC
August 2016

Y chromosome haplotype diversity in Mongolic-speaking populations and gene conversion at the duplicated STR DYS385a,b in haplogroup C3-M407.

J Hum Genet 2016 Jun 25;61(6):491-6. Epub 2016 Feb 25.

Division of Molecular and Forensic Genetics, Department of Forensic Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Y chromosome microsatellite (Y-STR) diversity has been studied in different Mongolic-speaking populations from South Siberia, Mongolia, North-East China and East Europe. The results obtained indicate that the Mongolic-speaking populations clustered into two groups, with one group including populations from eastern part of South Siberia and Central Asia (the Buryats, Barghuts and Khamnigans) and the other group including populations from western part of Central Asia and East Europe (the Mongols and Kalmyks). High frequency of haplogroup C3-M407 (>50%) is present in the Buryats, Barghuts and Khamnigans, whereas in the Mongols and Kalmyks its frequency is much lower. In addition, two allelic combinations in DYS385a,b loci of C3-M407 haplotypes have been observed: the combination 11,18 (as well as 11,17 and 11,19) is frequent in different Mongolic-speaking populations, but the 11,11 branch is present mainly in the Kalmyks and Mongols. Results of locus-specific sequencing suggest that the action of gene conversion is a more likely explanation for origin of homoallelic 11,11 combination. Moreover, analysis of median networks of Y-STR haplotypes demonstrates that at least two gene conversion events can be revealed-one of them has probably occurred among the Mongols, and the other event occurred in the Barghuts. These two events give an average gene conversion rate range of 0.24-7.1 × 10(-3) per generation.
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http://dx.doi.org/10.1038/jhg.2016.14DOI Listing
June 2016

RNA isolation from bloodstains collected on FTA cards - application in clinical and forensic genetics.

Arch Med Sadowej Kryminol 2016 ;66(4):244-254

Aim of the study: In recent years, RNA analysis has been increasingly used in clinical and forensic genetics. Nevertheless, a major limitation of RNA-based applications is very low RNA stability in biological material, due to the RNAse activity. This highlights the need for improving the methods of RNA collection and storage. Technological approaches such as FTA Classic Cards (Whatman) could provide a solution for the problem of RNA degradation. However, different methods of RNA isolation from FTA cards could have diverse effects on RNA quantity and quality. The purpose of this research was to analyze the utility of three different methods of RNA isolation from peripheral blood collected on FTA Classic Cards (Whatman). The study also aimed at assessing RNA stability in bloodstains deposited on FTA cards. Material and methods: The study was performed on peripheral bloodstains collected from 59 individuals on FTA Classic Cards (Whatman). RNA was isolated with High Pure RNA Isolation Kit (Roche Diagnostics), Universal RNA/miRNA Purification (EURx) and TRIzol Reagent (Life Technologies). RNA was subjected to quantitative analysis followed by reverse transcription and Real - Time PCR reaction. Results: The study has shown that FTA Classic Cards (Whatman) are useful tools for storing bloodstains at room temperature for RNA analysis. Moreover, the method of RNA extraction employing TRIzol Reagent (Life Technologies) provides the highest efficiency and reproducibility for samples stored for no more than 2 years. Conclusions: The FTA cards are suitable for collecting and storing bloodstains for RNA analysis in clinical and forensic genetics.
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http://dx.doi.org/10.5114/amsik.2016.66706DOI Listing
August 2017

On the origin of mongrels: evolutionary history of free-breeding dogs in Eurasia.

Proc Biol Sci 2015 12;282(1820):20152189

Museum and Institute of Zoology, Polish Academy of Sciences, Wilcza 64, Warszawa 00-679, Poland

Although a large part of the global domestic dog population is free-ranging and free-breeding, knowledge of genetic diversity in these free-breeding dogs (FBDs) and their ancestry relations to pure-breed dogs is limited, and the indigenous status of FBDs in Asia is still uncertain. We analyse genome-wide SNP variability of FBDs across Eurasia, and show that they display weak genetic structure and are genetically distinct from pure-breed dogs rather than constituting an admixture of breeds. Our results suggest that modern European breeds originated locally from European FBDs. East Asian and Arctic breeds show closest affinity to East Asian FBDs, and they both represent the earliest branching lineages in the phylogeny of extant Eurasian dogs. Our biogeographic reconstruction of ancestral distributions indicates a gradual westward expansion of East Asian indigenous dogs to the Middle East and Europe through Central and West Asia, providing evidence for a major expansion that shaped the patterns of genetic differentiation in modern dogs. This expansion was probably secondary and could have led to the replacement of earlier resident populations in Western Eurasia. This could explain why earlier studies based on modern DNA suggest East Asia as the region of dog origin, while ancient DNA and archaeological data point to Western Eurasia.
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http://dx.doi.org/10.1098/rspb.2015.2189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685779PMC
December 2015

Searching for association of the CAG repeat polymorphism in the mitochondrial DNA polymerase gamma gene (POLG) with colorectal cancer.

Acta Biochim Pol 2015 28;62(3):625-7. Epub 2015 Aug 28.

The Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum, Institute of Forensic Medicine, Department of Molecular and Forensic Genetics, Bydgoszcz, Poland.

Mitochondrial DNA polymerase gamma (POLG) is the only DNA polymerase involved in maintaining the mitochondrial genome. Recent studies demonstrated an association of CAG repeat polymorphism in the second exon of POLG gene with the risk of cancer. We investigated the CAG repeat variability in the POLG gene in tumor and non-tumor tissues from colorectal cancer patients and in DNA samples isolated from blood obtained from age-matched healthy persons. Somatically occuring CAG-repeat alterations in cancer tissues have been observed in 10% of patients, but no association has been found between the CAG repeat variants in the POLG gene and colorectal cancer risk.
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http://dx.doi.org/10.18388/abp.2014_935DOI Listing
July 2016
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