Bridging the gap: Short structural variants in the genetics of anorexia nervosa.

Anorexia nervosa (AN) is a devastating disorder with evidence of underexplored heritability. Twin and family studies estimate heritability (h ) to be 57%-64%, and genome-wide association studies (GWAS) reveal significant genetic correlations with psychiatric and anthropometric traits and a total of nine genome-wide significant loci. Whether significantly associated single nucleotide polymorphisms identified by GWAS are causal or tag true causal variants, remains to be elucidated.

Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

Background: Epstein-Barr virus (EBV) infection represents a major environmental risk factor for multiple sclerosis (MS), with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1)-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.

Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

Objective: The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk.

Methods: We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing.

High-avidity, high-IFNγ-producing CD8 T-cell responses following immune selection during HIV-1 infection.

HIV-1 mutations, which reduce or abolish CTL responses against virus-infected cells, are frequently selected in acute and chronic HIV infection. Among population HIV-1 sequences, immune selection is evident as human leukocyte antigen (HLA) allele-associated substitutions of amino acids within or near CD8 T-cell epitopes. In these cases, the non-adapted epitope is susceptible to immune recognition until an escape mutation renders the epitope less immunogenic.

Only slight impact of predicted replicative capacity for therapy response prediction.

Background: Replication capacity (RC) of specific HIV isolates is occasionally blamed for unexpected treatment responses. However, the role of viral RC in response to antiretroviral therapy is not yet fully understood.

Materials And Methods: We developed a method for predicting RC from genotype using support vector machines (SVMs) trained on about 300 genotype-RC pairs.

Effects of HIV type-1 immune selection on susceptability to integrase inhibitor resistance.

Background: All site-specific interactions between HIV type-1 (HIV-1) subtype, human leukocyte antigen (HLA)-associated immune selection and integrase inhibitor resistance are not completely understood. We examined naturally occurring polymorphisms in HIV-1 integrase sequences from 342 antiretroviral-naive individuals from the Western Australian HIV Cohort Study and the Swiss HIV Cohort Study.

Methods: Standard bulk sequencing and sequence-based typing were used to generate integrase sequences and high-resolution HLA genotypes, respectively.

Superiority of infectivity-based over particle-based methods for quantitation of drug resistant HIV-1 as inocula for cell cultures.

Performance of phenotypic assays and replication capacity assays require normalization of virus input. Therefore, quantitation of HIV-1 in supernatants to inoculate cell cultures is an important step. Since the gold standard for the determination of infectivity, the tissue culture infectious dose 50% (TCID50) is time-consuming, several other methods are in use.

No evidence for persistence of multidrug-resistant viral strains after a 7-month treatment interruption in an HIV-1-infected individual.

The number of HIV-1-infected patients harboring multidrug-resistant viruses is increasing. Since new antiretroviral drugs with favorable resistance profiles are limited, innovative strategies are urgently needed. Treatment interruptions can lead to a loss in HIV resistance followed by improved response to reinitiated therapy.