Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice

The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen's ability to adapt to the variable immune pressures exerted by the host. Understanding this interplay has proven difficult, largely because experimentally tractable animal models do not recapitulate the heterogeneity of tuberculosis disease. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to create a resource for associating bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and produce qualitatively distinct immune states. Global analysis of Mtb transposon mutant fitness (TnSeq) across the CC panel revealed that many virulence pathways are only required in specific host microenvironments, identifying a large fraction of the pathogen's genome that has been maintained to ensure fitness in a diverse population. Both immunological and bacterial traits can be associated with genetic variants distributed across the mouse genome, making the CC a unique population for identifying specific host-pathogen genetic interactions that influence pathogenesis

The exon 13 duplication in the BRCA1 gene is a founder mutation present in geographicaly diverse populations

Recently, a 6-kb duplication of exon 13, which creates a frameshift in the coding sequence of the BRCA1 gene, has been described in three unrelated U.S. families of European ancestry and in one Portuguese family. Here, our goal was to estimate the frequency and geographic diversity of carriers of this duplication. To do this, a collaborative screening study was set up that involved 39 institutions from 19 countries and included 3,580 unrelated individuals with a family history of the disease and 934 early-onset breast and/or ovarian cancer cases. A total of 11 additional families carrying this mutation were identified in Australia (1), Belgium (1), Canada (1), Great Britain (6), and the United States (2). Haplotyping showed that they are likely to derive from a common ancestor, possibly of northern British origin. Our results demonstrate that it is strongly advisable, for laboratories carrying out screening either in English-speaking countries or in countries with historical links with Britain, to include within their BRCA1 screening protocols the polymerase chain reaction-based assay described in this report

Spatiotemporal variability in bigeye vertical distribution in the Pacific

Bigeye tuna are targeted by longliners and caught incidentally by purse seiners in the tropical Pacific. The spawning biomass has been reduced significantly from unexploited levels, necessitating management action in both the western and central Pacific and eastern Pacific. Stock assessments of bigeye tuna rely primarily on data from the fisheries; however, the vulnerability of the stock to these gears, and its spatiotemporal variability, remains poorly understood, requiring simplifying assumptions to be made in the stock assessments. We analyzed the vertical behavior of 65 bigeye tuna (estimated size range 48–130 cm fork length) tracked with archival tags in the equatorial Pacific Ocean and the Coral Sea, and found that fish depth shows a clear gradient with longitude, becoming progressively shallower from west to east. Additive mixed models were used to explore potential relationships of the depth behavior during both day and night to several life history and environmental variables. Swimming depths were most clearly related to the thermocline depth, the intensity of temperature stratification of the water column and fish size. The model predictions suggest strong relationships between fish depth and fisheries catch-per-unit-effort (CPUE) both spatially and temporally. In particular, we propose that El Niño-Southern Oscillation-driven changes in oceanography have a major influence on fish depth and longline CPUE, which could have substantial implications for stock assessments where longline CPUE is used as an index of abundance

Role Strain in African-American Women

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67399/2/10.1177_002193478902000203.pd