The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection

Persistent differences in asthma self-efficacy by race, ethnicity, and income in adults with asthma

OBJECTIVE: The objective of this population-based study was to determine if and to what extent there are differences in asthma self-efficacy by race/ethnicity and income, and whether health status, levels of acculturation, and health care factors may explain these differences. METHODS: We conducted a secondary data analysis of asthma self-efficacy using the 2009 and 2011-2012 California Health Interview Survey, in adults with asthma (n = 7874). In order to examine if and how the effect of race /ethnicity and income on asthma self-efficacy may have been altered by health status, acculturation, and health care factors, we used staged multivariable logistic regression models. We conducted mediation analyses to evaluate which of these factors might mediate disparities in self-efficacy by race/ethnicity and income. RESULTS: 69.8% of adults reported having high asthma self-efficacy. Latinos (OR 0.66; 95% CI 0.51–0.86), African-Americans (OR 0.50; 95% CI 0.29–0.83), American Indian/Alaskan Natives (OR 0.55; 95% CI 0.31–0.98), and Asian/Pacific Islanders (OR 0.34; 95% CI 0.23–0.52) were less likely to report high self-efficacy compared to Whites. Individuals with income below the federal poverty level (OR 0.56; 95% CI 0.40-0.78) were less likely to report high self-efficacy compared to higher income individuals. The relationship between income and self-efficacy was no longer significant after further adjustment for health care factors; however, the differences in race and ethnicity persisted. Receiving an asthma management plan mediated the relationship in certain subgroups. CONCLUSIONS: Addressing modifiable health care factors may play an important role in reducing disparities in asthma self-efficacy

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu