Thyroid Stimulating Hormone Receptor Transcripts in Correlation with Clinical Parameters in Thyroid Carcinoma Patients

BACKGROUND: Differentiated thyroid carcinomas (DTC) preserve expression of thyroid stimulating hormone receptor (TSHR). AIM: The aim of our study was to evaluate the expression of mRNA-TSHR in peripheral blood of DTC patients, then to correlate the expression with clinical features: Serum thyroglobulin (sTg) value, initial staging and findings from the whole body scan (WBS), neck ultrasound (US), and total received dose of radioiodine therapy. MATERIALS AND METHODS: Forty patients were divided into three groups according to the treatment response: Patients with incomplete structural response (TCs), incomplete biochemical response (TCb), and excellent responders (TCr). Total RNA was isolated from peripheral blood and used for two-step reverse transcriptase-PCR with appropriate primers. Relative quantification using the ΔCt and 2–ΔΔCt and method was applied. sTg levels were evaluated with chemiluminescent assay. The statistical analysis was performed with Spearman Rank Order Correlation. RESULTS: We found that TCs patients expressed mRNA-TSHR by a 5.37-fold higher level than TCr patients, TCb patients expressed TSHR by an 8.88-fold higher level than TCr patients. A significant negative correlation was detected between sTg and ΔCt (CtTSHR - CtGAPDH) value (R = −0.475; p < 0.05), and between WBS/US findings and ΔCt (R= −0.321; p < 0.05). CONCLUSION: Our data revealed higher expression of mRNA-TSHR in peripheral blood of TCs and TCb compared to TCr patients and analysis revealed a significant correlation between mRNA-TSHR and sTg and US/WBS findings. Further studies with larger number of subjects and absolute quantification are needed for understanding the real meaning of mRNA-TSHR as a biomarker in DTC

Forensic DNA databasesin Western Balkan region:retrospectives, perspectives, and initiatives

The European Network of Forensic Science Institutes (ENFSI) recommended the establishment of forensic DNA databases and specific implementation and management legislations for all EU/ENFSI members. Therefore, forensic institutions from Bosnia and Herzegovina, Serbia, Montenegro, and Macedonia launched a wide set of activities to support these recommendations. To assess the current state, a regional expert team completed detailed screening and investigation of the existing forensic DNA data repositories and associated legislation in these countries. The scope also included relevant concurrent projects and a wide spectrum of different activities in relation to forensics DNA use. The state of forensic DNA analysis was also determined in the neighboring Slovenia and Croatia, which already have functional national DNA databases. There is a need for a ‘regional supplement’ to the current documentation and standards pertaining to forensic application of DNA databases, which should include regional-specific preliminary aims and recommendations

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

A comprehensive mutation study in wide deep-rooted R1 b Serbian pedigree: mutation rates and male relative differentiation capacity of 36 Y-STR markers

Haplotyping of Y-chromosomal short tandem repeats (Y-STRs) reflects the paternal lineage, although, the father-son pair profiles may differ due to the germline mutations. In order to discriminate between closely related males in criminal cases, as well as for the correct application of Y-STRs in the paternity/kinship analysis and determination of the most recent common ancestor in the familial searching or genealogy research, the assessment of mutation rates of routinely used Y-STRs is of a great importance. We genotyped 120 males belonging to one wide deep-rooted pedigree separated by 1-20 meiosis. The haplotypes of analyzed males distributed over 12 different families (according to their surnames), with 113 originating from one ancestor, and the remaining 7 from the second, closely related to the previous one, belong to the Rlb haplogroup. The analysis was performed using Powerplex (R) Y23 kit, Yfiler (TM) plus kit and 13 rapidly mutating (RM13) Y-STRs. In 20,855 allele transmissions, 175 mutations (61% repeat losses and 39% gains) and one gene conversion event were found at 25 out of 36 markers. The medians of locus-specific mutation rates estimated using the Bayesian approach ranged from 1.42 x 10 (-3) (95% credible interval (CI): 0.05 x 10(-3)- 7.56 x 10(-3)) for loci with no observed mutations to 130.91 x 10(-3) (95% CI: 102.91 x 10(-3) - 162.78 x 10(-3)) for DYF399S1, with a median rate across all 36 markers of 10.06 x 10(-3) (95% CI: 8.65 x 10(-3)- 11.61 x 10(-3)). In 6349 male relative pairs, the 36 Y-STR set distinguished 98.4% relative pairs by at least one mutation, compared to 95.9%, 65.5% and 57.4% for RM13, Yfiler (TM) plus, and Powerplex (R) Y23 set, respectively. The extra-pair paternity rate was estimated at 11.9 x 10(-3) (95% CI: 4.4 x 10(-3)- 25.8 x 10(-3)) fitting within the range reported for some European populations. A significant positive correlation was observed between fathers' ages at the time of the Y chromosome transmission and mutability rates (R-2 = 0.9495, p = 0.0256), with more significant results when analyzing RM markers (R-2 = 0.9827, p = 0.0087)

Standing at the Gateway to Europe - The Genetic Structure of Western Balkan Populations Based on Autosomal and Haploid Markers

<div><p>Contemporary inhabitants of the Balkan Peninsula belong to several ethnic groups of diverse cultural background. In this study, three ethnic groups from Bosnia and Herzegovina - Bosniacs, Bosnian Croats and Bosnian Serbs - as well as the populations of Serbians, Croatians, Macedonians from the former Yugoslav Republic of Macedonia, Montenegrins and Kosovars have been characterized for the genetic variation of 660 000 genome-wide autosomal single nucleotide polymorphisms and for haploid markers. New autosomal data of the 70 individuals together with previously published data of 20 individuals from the populations of the Western Balkan region in a context of 695 samples of global range have been analysed. Comparison of the variation data of autosomal and haploid lineages of the studied Western Balkan populations reveals a concordance of the data in both sets and the genetic uniformity of the studied populations, especially of Western South-Slavic speakers. The genetic variation of Western Balkan populations reveals the continuity between the Middle East and Europe via the Balkan region and supports the scenario that one of the major routes of ancient gene flows and admixture went through the Balkan Peninsula.</p></div

Principal component (PC) analysis of the variation of autosomal SNPs in Western Balkan populations in Eurasian context (PC1 <i>versus</i> PC2; see Table S1 for population data).

<p>Principal component (PC) analysis of the variation of autosomal SNPs in Western Balkan populations in Eurasian context (PC1 <i>versus</i> PC2; see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105090#pone.0105090.s022" target="_blank">Table S1</a> for population data).</p

Map of the Western Balkan region with triangles corresponding to the regions from where blood samples were collected.

<p>The sample of Bosnia and Herzegovina consisted of subsamples of three main ethnic groups: Bosniacs (Sarajevo and Zavidovici), Bosnian Croats (Central Bosnia - Zepce and Maglaj; South Bosnia and Herzegovina - Mostar, Grude, Livno, Capljina), Bosnian Serbs (Doboj and Banjaluka region); Croatia (mainland, Zagreb region), Serbia (Belgrade region), Montenegro (Podgorica), Kosovo (Pristina and Prizren) and Macedonia (Skopje).</p

TreeMix analysis of Western Balkan and surrounding populations (see Table S1 for population data).

<p>TreeMix graph represents the model of 10 gene-flow events within the sample. A. The population tree with gene-flow (migration) events. The scalebar specifies the weight of a migration, precise value of it is shown on the migration edges; B. Residuals plot; C. Ultrametric tree.</p

Average number of <i>ibd</i> segments per pair shared between Muslim Western Balkan populations (A – Bosniacs; B - Kosovars) and Middle Eastern (Saudis, Iranians, Syrians, Turks, Palestinians) and other non-Muslim Western Balkan populations (Bosnian Croats and Serbs, Croatians, Macedonians, Serbians, Montenegrins).

<p>Average number of <i>ibd</i> segments per pair shared between Muslim Western Balkan populations (A – Bosniacs; B - Kosovars) and Middle Eastern (Saudis, Iranians, Syrians, Turks, Palestinians) and other non-Muslim Western Balkan populations (Bosnian Croats and Serbs, Croatians, Macedonians, Serbians, Montenegrins).</p