ERAP1 and HLA-C*06 are strongly associated with the risk of psoriasis in the population of northern Poland.

INTRODUCTION: HLA-C*06 is a major psoriasis genetic risk marker. Recent reports have been focused on the role of different polymorphisms within genes involved in the functioning of the epidermal barrier and antigen processing in the pathogenesis of psoriasis. Data on the association between genetic variants of LCE3B_LCE3C, CSTA, ERAP1, ZAP70 and this dermatosis in the population from Eastern Europe are lacking. AIM: To compare the association between known genetic risk markers and psoriasis in a cohort of northern Polish patients with psoriasis and healthy controls. MATERIAL AND METHODS: Based on previous studies' results, five susceptibility loci: HLA-C, LCE3C_LCE3B, ERAP1, ZAP70 and CSTA were selected for genotyping in 148 patients with chronic plaque psoriasis and 146 healthy controls. Each patient with this disease was clinically assessed with the Psoriasis Area and Severity Index. RESULTS: The study population showed a significant association of psoriasis and a single nucleotide polymorphism in the ERAP1 - rs26653 (p = 3.11 × 10-5) and HLA-C*06 allele (p = 1.02 × 10-11) when compared with the control group. The presence of HLA-C*06 or rs26653 G allele significantly increased the risk of psoriasis by 2.4 times or twice, respectively. Carrying rs26653 C allele considerably decreased the risk of psoriasis by 1.5 times. CONCLUSIONS: In the context of pathogenesis of psoriasis, our findings might give the evidence on disturbances in the proteolytic processing of N-terminal fragments of antigens presented via major histocompatibility complex class I to T cells.

Evaluation of Psoriasis Genetic Risk Based on Five Susceptibility Markers in a Population from Northern Poland.

Psoriasis genetic background depends on polygenic and multifactorial mode of inheritance. As in other complex disorders, the estimation of the disease risk based on individual genetic variants is impossible. For this reason, recent investigations have been focused on combinations of known psoriasis susceptibility markers in order to improve the disease risk evaluation. Our aim was to compare psoriasis genetic risk score (GRS) for five susceptibility loci involved in the immunological response (HLA-C, ERAP1, ZAP70) and in the skin barrier function (LCE3, CSTA) between patients with chronic plaque psoriasis (n = 148) and the control group (n = 146). A significantly higher number of predisposing alleles was observed in patients with psoriasis in comparison to healthy individuals (6.1 vs. 5.2, respectively; P = 8.8×10-7). The statistical significance was even more profound when GRS weighted by logarithm odds ratios was evaluated (P = 9.9×10-14). Our results demonstrate the developed panel of five susceptibility loci to be more efficient in predicting psoriasis risk in the Polish population and to possess higher sensitivity and specificity for the disease than any of the markers analyzed separately, including the most informative HLA-C*06 allele.

[Analysis of mutations in father-son pairs within selected Y-STR loci]. / Analiza czestosci mutacji w parach ojciec-syn w wybranych markerach Y-STR.

The objective of the study was to examine the mutation rates of Y-chromosomal STR from father-son pairs. The paternity in these cases was confirmed previously with the use of autosomal STR system performing standard analyses of genetic profiles of the mother, child and putative father (PI > = 100000). We examined 200 father-son sample pairs from Northern Poland using the Y-STR 18-plex. We identified eleven mutations. Five mutations resulted in the gain of a repeat in the sons' chromosome and six resulted in a loss of a repeat. All the samples resulted in single repeat mutations from one sample, which contained a two repeat loss at DYS385. The overall average mutation rate estimate was 0.0031.There was no significant difference in the mutation rate between Y-STR loci of the 200 tested father-son pairs and the YHRD base.

[Examples of application of X chromosomal markers in familial investigations and personal identification]. / Przyklady zastosowania markerów chromosomu X w badaniach rodzinnych i identyfikacyjnych.

Besides autosomal STR loci, markers of sex chromosomes, X and Y, are increasingly more commonly used in genetic analyses aiming at paternity testing or personal identification. The paper presents cases in which analysis of microsatellite loci of the X chromosome (X-STRs) was included in the routine examination and allowed for an unambiguous determination of the relationship between the tested individuals. The cases addressed paternity testing of female children, determination whether the examined women were paternal half-sisters, as well as personal identification of a deceased man. In none of the conducted expert opinions, the putative father's DNA sample was't available. Genotyping of X-STR markers was carried out with the use of commercial kits: Mentype Argus X-8 PCR Amplification Kit (Biotype) and Investigator Argus X-12 Kit (Qiagen).

Analysis of forensically used autosomal short tandem repeat markers in Polish and neighboring populations.

The purpose of this study was to evaluate the homogeneity of Polish populations with respect to STRs chosen as core markers of the Polish Forensic National DNA Intelligence Database, and to provide reference allele frequencies and to explore the genetic interrelationship between Poland and neighboring countries. The allele frequency distribution of 10 STRs included in the SGMplus kit was analyzed among 2176 unrelated individuals from 6 regional Polish populations and among 4321 individuals from Germany (three samples), Austria, The Netherlands, Sweden, Czech Republic, Slovakia, Belarus, Ukraine and the Russian Federation (six samples). The statistical approach consisted of AMOVA, calculation of pairwise Rst values and analysis by multidimensional scaling. We found homogeneity of present day Poland and consistent differences between Polish and German populations which contrasted with relative similarities between Russian and German populations. These discrepancies between genetic and geographic distances were confirmed by analysis of an independent data set on Y chromosome STRs. Migrations of Goths, Viking influences, German settlements in the region of Volga river and/or forced population resettlements and other events related to World War II are the historic events which might have caused these finding.

[Personal identification of an unknown individual based on determination of his DNA profile from exhumed remains]. / Ustalenie tozsamosci nieznanej osoby w oparciu o okreslenie profilu DNA z ekshumowanych szczatków ludzkich.

The aim of the present investigation was personal identification of an unknown man whose remains were exhumed four years after burial. The femur of the deceased was secured for the genetic analysis. The comparative material included buccal swabs collected from the putative relatives of the deceased, i.e. the wife, son and brother. Genomic DNA was extracted from the bone using two methods: traditional isolation with phenol/chloroform and as a alternative technique, a simple and rapid method described by T. Kalmár et al. The results were then compared. The specimens underwent DNA amplification using the AmpFISTRSEfiler PCR Amplification Kit. The authors obtained a full STR profile of the unknown man from each isolate, yet the DNA extraction method proposed by T. Kalmár et al. allowed for simpler and faster isolation of genetic material. The statistical analysis of the obtained results confirmed the paternity of the deceased and established his son as his rightful child (P = 99.999999%), also confirming the consanguinity between the investigated individual and his putative brother (P = 99.9999%).

Belarusian population genetic database for 15 autosomal STR loci.

Allele frequencies of 15 short tandem repeat loci included in the AmpFlSTR Identifiler kit (Applied Biosystems) were obtained from a sample set of unrelated individuals living in Belarus (n=176). For all loci, no deviation from Hardy-Weinberg equilibrium was found. Results were compared with data available for the Belarusian minority residing in northeastern Poland and for other Slavic populations. Statistically significant differences were observed between Belarusians and all compared populations. The values of heterozygosity, polymorphic information content (PIC), power of discrimination (PD), power of exclusion (PE), paternity index (PI) and matching probability (pM) were calculated.

[Population study of four X-chromosomal STR loci from the northern part of Poland]. / Badanie polimorfizmu czterech loci STR chromosomu X w populacji Polski pólnocnej.

UNLABELLED: INTRODUCTION, MATERIALS AND METHODS: The allele frequencies of four short tandem repeats (STR) loci specific to the human X chromosome (DXS101, DXS7423, DXS8377 and phosphoribosyltransferase HPRTB) were analyzed by means of a multiplex PCR reaction in a sample of 200 unrelated individuals residing in the northern part of Poland. The separation and detection of PCR products were performed by capillary electrophoresis on the 3130 Genetic Analyzer. Testing for Hardy-Weinberg equilibrium (HWE) showed no significant deviation for these loci. RESULTS: Statistical parameters such as: heterozygosity observed, mean exclusion chance, power of discrimination in males and power of discrimination in females showed that the examined multiplex is useful in forensic and paternity testing applications.

Analysis of polymorphism of three human Y-chromosome STR loci: DYS390, DYS392 and DYS393 in the population of northern Poland.

The study aimed at development of a multiplex PCR system for amplification of three Y-chromosome STR loci: DYS390, DYS392 and DYS393, and its application in haplotype polymorphism analysis in the population of northern Poland. Due to interactions between originally published primers, a new DYS392 primer pair was proposed. In a population of 158 unrelated males, 28 different haplotypes could be observed, 12 of which were seen only once. The haplotype diversity is 0.805. Distribution of haplotypes of the studied loci is specific to the population of northern Poland and distinguishes it from compared West-European populations. To our knowledge, this is the first report on a Y-STR multiplex system that can be analysed on native polyacrylamide gels.