Sample Curation at a Lunar Outpost

The six Apollo surface missions returned 2,196 individual rock and soil samples, with a total mass of 381.6 kg. Samples were collected based on visual examination by the astronauts and consultation with geologists in the science back room in Houston. The samples were photographed during collection, packaged in uniquely-identified containers, and transported to the Lunar Module. All samples collected on the Moon were returned to Earth. NASA's upcoming return to the Moon will be different. Astronauts will have extended stays at an out-post and will collect more samples than they will return. They will need curation and analysis facilities on the Moon in order to carefully select samples for return to Earth

Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low–BMI cases are larger than those estimated from high–BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1×10−9). The improvement varied across diseases with a 16% median increase in χ2 test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Lunar meteorite Yamato-791197: A polymict anorthositic norite breccia

The lunar origin of Antarctic meteorite Yamato-791197 is confirmed by geochemical and petrologic studies of four subsamples of split 89. The meteorite has a bulk composition of ferroan anorthositic norite with very low incompatible element concentrations. It is a breccia containing clasts of igneous and metamorphic lunar highlands rocks, melt rocks and glasses derived from them by impact, and rare clasts of mare basalt. Y-791197 is similar in composition and clast assemblage to ALHA81005,but there are significant differences between the two meteorites in the ratio of Mg/Fe, concentrations of Sc and REE, and proportions of clast types. These differences are no greater than those observed among breccias ejected by a single lunar impact of modest size (1km crater), so the derivation of Y-791197 and ALHA81005 from a single impact is possible. Regional differences in clast assemblages between Apollo sites are much larger, so the similarities in clast assemblage between the two meteorites support the suggestion that they originated from the same region of the Moon. We conclude that the two meteorites were ejected from the Moon by the same impact. The lunar meteorites are very similar in composition to lunar granulitic breccias and to the estimated average composition of the lunar highlands, unlike most Apollo highlands soils and breccias which are enriched in a KREEP component. The dominance of plutonic anorthositic norite precursors in the granulites and their common occurrence in the lunar meteorites suggest that abundant quantities of anorthositic norites were produced during lunar crustal evolution