Tetra-allelic SNPs: Informative forensic markers compiled from public whole-genome sequence data

Multiple-allele single nucleotide polymorphisms (SNPs) are potentially useful for forensic DNA analysis as they can provide more discrimination power than normal binary SNPs. In addition, the presence in a profile of more than two alleles per marker provides a clearer indication of mixed DNA than assessments of imbalanced signals in the peak pairs of binary SNPs. Using the 1000 Genomes Phase III human variant data release of 2014 as the starting point, this study collated 961 tetra-allelic SNPs that pass minimum sequence quality thresholds and where four separate nucleotide substitution alleles were detected. Although most of these loci had three of the four alleles in combined frequencies of 2% or less, 160 had high heterozygosities with 50 exceeding those of ‘ideal’ 0.5:0.5 binary SNPs. From this set of most polymorphic tetra-allelic SNPs, we identified markers most informative for forensic purposes and explored these loci in detail. Subsets of the most polymorphic tetra-allelic SNPs will make useful additions to current panels of forensic identification SNPs and ancestry-informative SNPs. The 24 most discriminatory tetra-allelic SNPs were estimated to detect more than two alleles in at least one marker per profile in 99.9% of mixtures of African contributors. In European contributor mixtures 99.4% of profiles would show multiple allele patterns, but this drops to 92.6% of East Asian contributor mixtures due to reduced levels of polymorphism for the 24 SNPs in this population group.     

Next generation sequencing and its applications in forensic genetics

It has been almost a decade since the first next generation sequencing (NGS) technologies emerged and quickly changed the way genetic research is conducted. Today, full genomes are mapped and published almost weekly and with ever increasing speed and decreasing costs. NGS methods and platforms have matured during the last 10 years, and the quality of the sequences has reached a level where NGS is used in clinical diagnostics of humans. Forensic genetic laboratories have also explored NGS technologies and especially in the last year, there has been a small explosion in the number of scientific articles and presentations at conferences with forensic aspects of NGS. These contributions have demonstrated that NGS offers new possibilities for forensic genetic case work. More information may be obtained from unique samples in a single experiment by analyzing combinations of markers (STRs, SNPs, insertion/deletions, mRNA) that cannot be analyzed simultaneously with the standard PCR-CE methods used today. The true variation in core forensic STR loci has been uncovered, and previously unknown STR alleles have been discovered. The detailed sequence information may aid mixture interpretation and will increase the statistical weight of the evidence. In this review, we will give an introduction to NGS and single-molecule sequencing, and we will discuss the possible applications of NGS in forensic genetics.     

Occult infection with HBV intergenotypic A2/G recombinant following acute hepatitis B caused by an HBV/A2 isolate

Viral and host factors leading to occult hepatitis B virus (HBV) infection (OBI) are not fully understood. Whether HBV genotype may influence the occurrence and course of OBIs is unknown. Here, we describe the case of a patient infected with HBV genotype A2 who developed symptomatic acute hepatitis and did not seroconvert after loss of HBsAg and HBeAg. The acute phase of hepatitis B was followed by a period of more than 2 years during which the DNA of an intergenotypic HBV/A2/G recombinant was intermittently detected in serum.     

The Impact of Personality Traits on Ratings of Obsessive-Compulsive Symptoms

Objective

The goal of this study was to evaluate consistencies and discrepancies between clinician-administered and self-report versions of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and to examine relationships between these scales and personality traits.

Methods

A total of 106 patients with obsessive-compulsive disorder (OCD) participated in this study. All participants were assessed with both clinician-administered and self-report versions of the Y-BOCS. The Structured Clinical Interview for DSM-IV Axis II Disorders Personality Questionnaire (SCID-II-PQ) was used to evaluate relationships between personality traits and scores on the Y-BOCS.

Results

Scores on the clinician-administered Y-BOCS and its obsession subscale were significantly higher than were those on the self-report version. However, we found no significant differences in compulsion subscale scores. We also found that the discrepancies in the scores on the two versions of the Y-BOCS and its compulsion subscale were significantly positively correlated with scores for narcissistic personality traits on the SCID-II-PQ. Additionally, narcissistic personality traits had a significant effect on the discrepancy in the scores on the two versions of the Y-BOCS and its compulsion subscale in the multiple linear regression analysis.

Conclusion

This is the first study to elucidate relationships between personality traits and discrepancies between scores on the two versions of the Y-BOCS. Although clinicians tend to rate obsessive symptoms as being more severe than do patients, clinicians may underestimate the degree to which individuals with narcissistic personality traits suffer more from subjective discomfort due to compulsive symptoms. Therefore, the effect of personality traits on symptom severity should be considered in the treatment of OCD.     

Comparison of carpal tunnel injection techniques: A cadaver study

The purpose of the study was to evaluate the accuracy of injections into the carpal tunnel using three different portals in cadavers, and to define safe guidelines. In this study, 150 wrists of 75 cadavers (54 male, 21 female) were included. To compare three injection sites, 50 wrists of 25 cadavers were used for each technique; we used 23 gauge needles, and acrylic dye. The first injection technique: the needle was inserted 1cm proximal to the wrist crease and directed distally by roughly 45 in an ulnar direction through the flexor carpi radialis tendon. The second injection technique: the needle was inserted into the carpal tunnel from a point just ulnar to the palmaris longus tendon and 1cm proximal to the wrist crease. The third injection technique: the needle was inserted just distal to the distal skin crease of the wrist in line with the fourth ray. The first injection technique gave the highest accuracy rate, and this was also the safest injection site. Median nerve injuries caused by injection was seen mostly with the second technique. Although a steroid injection may provide symptomatic relief in patients with carpal tunnel syndrome, the median nerve and other structures in the carpal tunnel are at risk of injury. Because of that, the injection should be given using the correct technique by physicians skilled in carpal tunnel surgery.     

Expression analysis and clinical correlation of aquaporin 1 and 4 genes in human hippocampal sclerosis

Mesial temporal sclerosis (MTS) is the most frequent cause of drug resistant symptomatic partial epilepsy. The mechanism and genetic background of this unique pathology are not well understood. Aquaporins (AQP) are regulators of water homeostasis in the brain and are expressed in the human hippocampus. We explored the role of AQP genes in the pathogenetic mechanisms of MTS through an evaluation of gene expression in surgically removed human brain tissue. We analyzed AQP1 and 4 mRNA levels by quantitative real-time polymerase chain reaction and normalized to ABL and cyclophilin genes, followed by immunohistochemistry for AQP4. Relative expressions were calculated according to the delta Ct method and the results were compared using the Mann-Whitney U test. Brain specimens of 23 patients with epilepsy who had undergone surgery for MTS and seven control autopsy specimens were investigated. Clinical findings were concordant with previous studies and 61% of the patients were seizure-free in the postoperative period. AQP1 and 4 gene expression levels did not differ between MTS patients and control groups. Immunofluorescence analysis of AQP4 supported the expression results, showing no difference. Previous studies have reported contradictory results about the expression levels of AQP in MTS. To our knowledge, only one study has suggested upregulation whereas the other indicated downregulation of perivascular AQP4. Our study did not support these findings and may rule out the involvement of AQP in human MTS.     

The association between psychopathology of first-episode psychosis patients within the schizophrenia spectrum and previous offending

Patients with schizophrenia have been shown to have an increased risk of criminality. The aim was to describe possible psychopathological differences between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis. In a multi-centre study, 16 psychiatric treatment centres included and rated 477 patients with first-episode psychosis over a 2-year period on socio-demography, the Positive and Negative Syndrome Scale, OPerational CRITeria checklist, Global Assessment of Functioning, Premorbid Adjustment Scale and Self-report Insight Scale for psychosis. Data were linked with data concerning criminal and psychiatric history. No key characteristics were found to assist the early detection of criminal persons before first psychiatric hospital contact for a psychotic incident. However, when adjusted for sex, age, abuse, living conditions, marital status, employment status and education, a primarily positive symptomatology was associated with a prior criminal career. The premorbid level of functioning and several function parameters were also significantly associated with criminal history. There are significant differences in psychopathology between schizophrenia spectrum patients with and without a criminal career before first-episode psychosis, and a better screening procedure in the judicial system could detect these individuals earlier and make adequate treatment possible.     

Trends in suicidality amid the economic crisis in Greece

For the decade 2000–2010, suicidal rates appear to be both low and stable in Greece and unrelated to the socioeconomic environment. It is highly possible that the recent crisis caused a significant increase in dysphoria, stress, depression and maybe suicidal ideation in the general population, but completed suicides do not seem to have increased so far. Measures are needed to make sure there will be no increase in completed suicides in the near future, since historically, periods of socioeconomic instability might be related to increased suicidality. Community interventions reduce stigma and enhance help-seeking. However, only those including the creation of social support networks are essential in the fight against suicidality.     

Within-host heterogeneity and flexibility of mcr-1 transmission in chicken gut

ObjectivesTo characterize the colistin-resistant bacterial population in the gut and assess diversity of mcr-1 transmission within a single individual.MethodsLarge numbers of isolates (>100 colonies/chicken cecum sample) were collected from nine randomly selected mcr-1-positive chickens in China and used for comprehensive microbiological, molecular and comparative genomics analyses.ResultsOf 1273 colonies, 968 were mcr-1 positive (962 Escherichia coli, two Escherichia fergusonii, two Klebsiella pneumoniae and two Klebsiella quasipneumoniae). One to six colistin-resistant species and three to 10 E. coli pulsed-field gel electrophoresis (PFGE) clusters could be identified from each sample. Whole-genome sequencing (WGS) analysis of the representative E. coli strains revealed three to nine sequence types observed in a single chicken host. The mcr-1 genes are located in either chromosomes or plasmids of different types, including IncI2 (n=30), IncHI2 (n=14), IncX4 (n=4), p0111(n=2) and IncHI1(n=1). Strikingly, in single cecum samples, one to five Inc type plasmids harbouring mcr-1 could be identified. Great diversity was also observed for the same IncI2 plasmid within a single chicken host. In addition, up to eight genetic contexts of the mcr-1 gene occurred within a single chicken.ConclusionsThere is extensive heterogeneity and flexibility of mcr-1 transmission in chicken gut due to bacterial species differences, distant clonal relatedness of isolates, many types and variations of mcr-positive plasmids, and the flexible genetic context of the mcr-1 gene. These compelling findings indicate that the gut is a ‘melting pot’ for active horizontal transfer of the mcr-1 gene.