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This paper presents sex-related immunophenotypic differences in human stromal vascular fraction from lipospirate and microfragmented lipospirate detected by polychromatic flow cytometry when used in different clinical conditions

Aim To assess the prevalence of actionable pharmacogenetic interventions in patients who underwent pharmacogenetic testing with a multi- gene panel. Methods We retrospectively reviewed single-center electronic health records. A total of 319 patients were enrolled who underwent pharmacogenomic testing with the RightMed test panel using TaqMan quantitative real-time PCR method and copy number variation analysis to determine the SNPs in the 27 target genes. Results Actionable drug-gene pairs were found in 235 (73.7%) patients. Relevant guidelines on genotype- based prescribing were available for 133 (56.7%) patients at the time of testing. Based on the patients' genotype, 139 (43.6%) patients were using at least one drug with significant pharmacogenetic interactions. Conclusion Two out of three patients had at least one drug- gene pair in their therapy. Further studies should assess the clinical effectiveness of integrating pharmacogenomic data into patients' electronic health records.

© 2016 Macmillan Publishers Limited, part of Springer Nature. High-Coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long-and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.

Introduction Chronic low back pain (CLBP) produces considerable direct costs as well as indirect burdens for society, industry and health systems. CLBP is characterised by heterogeneity, inclusion of several pain syndromes, different underlying molecular pathologies and interaction with psychosocial factors that leads to a range of clinical manifestations. There is still much to understand in the underlying pathological processes and the non-psychosocial factors which account for differences in outcomes. Biomarkers that may be objectively used for diagnosis and personalised, targeted and cost-effective treatment are still lacking. Therefore, any data that may be obtained at the-omics' level (glycomics, Activomics and genome-wide association studies-GWAS) may be helpful to use as dynamic biomarkers for elucidating CLBP pathogenesis and may ultimately provide prognostic information too. By means of a retrospective, observational, case-cohort, multicentre study, we aim to investigate new promising biomarkers potentially able to solve some of the issues related to CLBP. Methods and analysis The study follows a two-phase, 1:2 case-control model. A total of 12 000 individuals (4000 cases and 8000 controls) will be enrolled; clinical data will be registered, with particular attention to pain characteristics and outcomes of pain treatments. Blood samples will be collected to perform-omics studies. The primary objective is to recognise genetic variants associated with CLBP; secondary objectives are to study glycomics and Activomics profiles associated with CLBP. Ethics and dissemination The study is part of the PainOMICS project funded by European Community in the Seventh Framework Programme. The study has been approved from competent ethical bodies and copies of approvals were provided to the European Commission before starting the study. Results of the study will be reviewed by the Scientific Board and Ethical Committee of the PainOMICS Consortium. The scientific results will be disseminated through peer-reviewed journals. Trial registration number NCT02037789; Pre-results.

© 2015 Karmin et al. It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836–0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father–son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database. ispartof: Human Mutation vol:35 issue:8 pages:1021-1032 status: published

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database. Published 2014 Wiley Periodicals, Inc.**

A recent genome-wide association study identified hepatocyte nuclear factor 1-alpha (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MOD?) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCE)-MODY (n = 118), hepatocyte nuclear factor 4-alpha (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic >= 0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction. Diabetes 62:1329-1337, 2013

STR markers are useful in establishing paternal linkages, kinship testing and familial searching, also finds its application in studying migration pattern of populations. Y STR haplotyping is particularly important for forensic analysis in case of rape, especially in those cases where more than one male was involved. New kit PowerPlex® Y23 enables the coamplification and 5- dye detection of 23 loci, 6 new loci(DYS576, DYS481, DYS549, DYS533, DYS570, DYS643) in comparison to Applied Biosystems and 11 new loci in comparison to previous PowerPlex Y kit which included 12 STR loci. Aim of this study was to indicate the significance of increasing the number of STR loci in forensic analysis. This study was conducted on referent sample of 100 unrelated males from Bosnia and Herzegovina. Genomic DNA was extracted from buccal swab using salting out method as well as QiagenDNeasy™ Tissue Kit. PCR amplifications have been carried out in PE GeneAmp PCR System Thermal Cycler. Y Chromosomal 23 STRs alleles were typed using ABI 310 Genetic Analyzer. Estimation of haplotype frequencies, haplotype diversity and average gene diversity were done using Arlequin Software V. 3.5. Ninety-eight unique haplotypes were detected, and one appeared two times. The most polymorphic locus is DYS418 on which we detected 14 alleles. Furthermore on this DYS418 locus we detected allele 33 which was not incorporated in allelic ladder provided by PowerPlex® Y23 kit. The least polymorphic loci in our study were DYS389I, DYS391, DYS437 and DYS393.

DNA Identification of Skeletal Remains: Retrospective and Perspective

We analyzed data on the junior researchers, using a sample of junior researchers whose fellowship supports from the Croatian Ministry of Science, Education and Sports were terminated between 1999 and 2005. The study included 1, 320 junior researchers, of whom 434 completed a PhD degree (32.9%). Junior researchers in natural sciences were the most effective in completing a PhD degree (54.7%), while those in biomedicine were the least effective (17.1%). Junior researchers in natural sciences also had the longest employment duration. Completing a PhD degree was positively associated with female gender (logistic regression odds ratio OR=1.38), co-authoring a scientific article with the mentor (OR=2.27), and above-average scientific production of the junior researcher (OR=2.21). Junior researchers who were among top 10% of students according to their grade point average during undergraduate studies had significantly lower odds of completing a PhD degree during fellowship (OR=0.23), as well as junior researchers who were employed in biomedicine (OR=0.22). The study results indicate the potential points which could be influenced during the junior researchers selection process and at the moment of granting fellowships, both with an aim to improve the effectiveness of the junior researcher fellowship support system in the Republic of Croatia.

Aim: To study the distribution of allele frequencies of 15 short tandem repeat (STR) loci in a representative sample of Croatian population. Methods: A total of 195 unrelated Caucasian individuals born in Croatia, from 14 counties and the City of Zagreb, were sampled for the analysis. All the tested individuals were voluntary donors. Buccal swab was used as the DNA source. AmpFlSTR® ; ; Identifiler® ; ; was applied to simultaneously amplify 15 STR loci. Total reaction volume was 12.5 μ L. The PCR amplification was carried out in PE Gene Amp PCR System Thermal Cycler. Electrophoresis of the amplification products was preformed on an ABI PRISM 3130 Genetic Analyzer. After PCR amplification and separation by electrophoresis, raw data were compiled, analyzed, and numerical allele designations of the profiles were obtained. Deviation from Hardy-Weinberg equilibrium, observed and expected heterozygosity, power of discrimination, and power of exclusion were calculated. Bonferroni’ s correction was used before each comparative analysis. Results: We compared Croatian data with those obtained from geographically neighboring European populations. The significant difference (at P

The role of DNA technology in identification of skeletal remains discovered in mass graves: Croatian and Bosnian experience

An evaluazion of complex Y-chromosome landscape of South-East Europe trough different markers.

Preliminary population study at fifteen autosomal and twelve Y-chromosome short tandem repeat loci in the representative sample of multinational Bosnia and Herzegovina residents

With the advance in typing tools and extraction procedures in recent years, DNA analysis has developed into an amazingly powerful method for forensic analysis. For a number of years, autosomal STR (Short Tandem Repeat) typing has been used as a tool in the process of identification of war victims in Croatia. Although DNA typing is very effective in detecting possible identities of exhumed skeletal remains, this approach bears some risk of false identification. The paper presents the case of a match between skeletal remains and the son and wife of a missing person in 13 STR loci. Even though these skeletal remains also matched in 13 loci the mother of the same missing person, additional genetic testing (Y-chromosome and mitochondrial DNA) unequivocally excluded the proposed identity. Although likelihood ratio is the best measure of the significance of a genetic match between exhumed skeletal remains and relatives of the missing person, the meaning of likelihood ratio is not as clear in database matching as in simple paternity cases and great care is needed to avoid wrong interpretation. To reduce the risk of possible false identifications, in addition to DNA evidence, other types of evidence (such as information about the time, place and other conditions of disappearance), as well as on anthropological and other »classical« forensic data are being used as a »control mechanism« in the DNA-lead process. Zahvaljujući stalnom napretku u metodama izolacije i karakterizacije, analiza DNA razvila se u vrlo moćnu metodu forenzičke analize. Već niz godina analizu autosomnih STR regija primjenjuje se kao temeljnu metodu u procesu identifikacije žrtava rata u Hrvatskoj. Iako je analiza DNA vrlo učinkovita u pronalaženju mogućega identiteta ekshumiranih posmrtnih ostataka, ovakav pristup nosi i određeni rizik pogrešne identifikacije. Ovdje je opisan slučaj poklapanja posmrtnih ostataka sa sinom i suprugom nestale osobe u 13 STR lokusa. Iako su se isti posmrtni ostaci također poklapali i s majkom iste nestale osobe u 13 lokusa, dodatnim genetičkim ispitivanjima (Y kromosom i mitohondrijska DNA) nedvojbeno je isključena mogućnost da se radi o toj osobi. Omjer vjerojatnosti najbolji je pokazatelj značajnosti genetičkoga podudaranja skeletnih ostataka i rodbine nestalih osoba, no kad je to podudaranje pronađeno nasumičnim pretraživanjem baze podataka, značaj omjera vjerojatnosti nije tako jasan kao u jednostavnome utvrđivanju očinstva i potreban je velik oprez kako ne bi došlo do njegove pogrešne interpretacije. Radi smanjivanja rizika pogrešne identifikacije, osim na rezultate analize DNA, pri utvrđivanju identiteta velik značaj potrebno je dati i drugim tipovima dokaza (poput vremena, lokacije i uvjeta nestanka) te antropološkim i ostalim »klasičnim« forenzičkim dokazima, kao kontrolnome mehanizmu u procesu identifikacije predvođenom analizom DNA.