Origin and evolution of the octoploid strawberry genome.

Cultivated strawberry emerged from the hybridization of two wild octoploid species, both descendants from the merger of four diploid progenitor species into a single nucleus more than 1 million years ago. Here we report a near-complete chromosome-scale assembly for cultivated octoploid strawberry (Fragaria × ananassa) and uncovered the origin and evolutionary processes that shaped this complex allopolyploid. We identified the extant relatives of each diploid progenitor species and provide support for the North American origin of octoploid strawberry. We examined the dynamics among the four subgenomes in octoploid strawberry and uncovered the presence of a single dominant subgenome with significantly greater gene content, gene expression abundance, and biased exchanges between homoeologous chromosomes, as compared with the other subgenomes. Pathway analysis showed that certain metabolomic and disease-resistance traits are largely controlled by the dominant subgenome. These findings and the reference genome should serve as a powerful platform for future evolutionary studies and enable molecular breeding in strawberry

Estimation of the Standardized Risk Difference and Ratio in a Competing Risks Framework: Application to Injection Drug Use and Progression to AIDS After Initiation of Antiretroviral Therapy

There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS

Off-target capture data, endosymbiont genes and morphology reveal a relict lineage that is sister to all other singing cicadas

Phylogenetic asymmetry is common throughout the tree of life and results from contrasting patterns of speciation and extinction in the paired descendant lineages of ancestral nodes. On the depauperate side of a node, we find extant ´relict´ taxa that sit atop long, unbranched lineages. Here, we show that a tiny, pale green, inconspicuous and poorly known cicada in the genus Derotettix, endemic to degraded salt-plain habitats in arid regions of central Argentina, is a relict lineage that is sister to all other modern cicadas. Nuclear and mitochondrial phylogenies of cicadas inferred from probe-based genomic hybrid capture data of both target and non-target loci and a morphological cladogram support this hypothesis. We strengthen this conclusion with genomic data from one of the cicada nutritional bacterial endosymbionts, Sulcia, an ancient and obligate endosymbiont of the larger plant-sucking bugs (Auchenorrhyncha) and an important source of maternally inherited phylogenetic data. We establish Derotettiginae subfam. nov. as a new, monogeneric, fifth cicada subfamily, and compile existing and new data on the distribution, ecology and diet of Derotettix. Our consideration of the palaeoenvironmental literature and host-plant phylogenetics allows us to predict what might have led to the relict status of Derotettix over 100 Myr of habitat change in South America.Fil: Simon, Chris. University of Connecticut; Estados UnidosFil: Gordon, Eric R. L.. University of Connecticut; Estados UnidosFil: Moulds, M.S.. Australian Museum Research Institute; AustraliaFil: Cole, Jeffrey A.. Pasadena City College; Estados UnidosFil: Haji, Diler. University of Connecticut; Estados UnidosFil: Lemmon, Alan R.. Florida State University; Estados UnidosFil: Lemmon, Emily Moriarty. Florida State University; Estados UnidosFil: Kortyna, Michelle. Florida State University; Estados UnidosFil: Nazario, Katherine. University of Connecticut; Estados UnidosFil: Wade, Elizabeth J.. Curry College. Department of Natural Sciences and Mathematics; Estados Unidos. University of Connecticut; Estados UnidosFil: Meister, Russell C.. University of Connecticut; Estados UnidosFil: Goemans, Geert. University of Connecticut; Estados UnidosFil: Chiswell, Stephen M.. National Institute of Water and Atmospheric Research; Nueva ZelandaFil: Pessacq, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Veloso, Claudio. Universidad de Chile; ChileFil: McCutcheon, John P.. University of Montana; Estados UnidosFil: Lukasik, Piotr. University of Montana; Estados Unidos. Swedish Museum of Natural History. Department of Bioinformatics and Genetics; Sueci

The DESI One-Percent Survey: Evidence for Assembly Bias from Low-Redshift Counts-in-Cylinders Measurements

We explore the galaxy-halo connection information that is available in low-redshift samples from the early data release of the Dark Energy Spectroscopic Instrument (DESI). We model the halo occupation distribution (HOD) from z=0.1-0.3 using Survey Validation 3 (SV3; a.k.a., the One-Percent Survey) data of the DESI Bright Galaxy Survey (BGS). In addition to more commonly used metrics, we incorporate counts-in-cylinders (CiC) measurements, which drastically tighten HOD constraints. Our analysis is aided by the Python package, galtab, which enables the rapid, precise prediction of CiC for any HOD model available in halotools. This methodology allows our Markov chains to converge with much fewer trial points, and enables even more drastic speedups due to its GPU portability. Our HOD fits constrain characteristic halo masses tightly and provide statistical evidence for assembly bias, especially at lower luminosity thresholds: the HOD of central galaxies in $z\sim0.15$ samples with limiting absolute magnitude $M_r < -20.0$ and $M_r < -20.5$ samples is positively correlated with halo concentration with a significance of 99.9% and 99.5%, respectively. Our models also favor positive central assembly bias for the brighter $M_r < -21.0$ sample at $z\sim0.25$ (94.8% significance), but there is no significant evidence for assembly bias with the same luminosity threshold at $z\sim0.15$. We provide our constraints for each threshold sample's characteristic halo masses, assembly bias, and other HOD parameters. These constraints are expected to be significantly tightened with future DESI data, which will span an area 100 times larger than that of SV3

The DESI One-percent Survey: Evidence for Assembly Bias from Low-redshift Counts-in-cylinders Measurements

We explore the galaxy-halo connection information that is available in low-redshift samples from the early data release of the Dark Energy Spectroscopic Instrument (DESI). We model the halo occupation distribution (HOD) from z = 0.1 to 0.3 using Survey Validation 3 (SV3; a.k.a., the One-Percent Survey) data of the DESI Bright Galaxy Survey. In addition to more commonly used metrics, we incorporate counts-in-cylinders (CiC) measurements, which drastically tighten HOD constraints. Our analysis is aided by the Python package, galtab, which enables the rapid, precise prediction of CiC for any HOD model available in halotools. This methodology allows our Markov chains to converge with much fewer trial points, and enables even more drastic speedups due to its GPU portability. Our HOD fits constrain characteristic halo masses tightly and provide statistical evidence for assembly bias, especially at lower luminosity thresholds: the HOD of central galaxies in z ∼ 0.15 samples with limiting absolute magnitude M r < −20.0 and M r < −20.5 samples is positively correlated with halo concentration with a significance of 99.9% and 99.5%, respectively. Our models also favor positive central assembly bias for the brighter M r < −21.0 sample at z ∼ 0.25 (94.8% significance), but there is no significant evidence for assembly bias with the same luminosity threshold at z ∼ 0.15. We provide our constraints for each threshold sample’s characteristic halo masses, assembly bias, and other HOD parameters. These constraints are expected to be significantly tightened with future DESI data, which will span an area 100 times larger than that of SV3

Local primordial non-Gaussianity from the large-scale clustering of photometric DESI luminous red galaxies

We use angular clustering of luminous red galaxies from the Dark Energy Spectroscopic Instrument (DESI) imaging surveys to constrain the local primordial non-Gaussianity parameter fNL. Our sample comprises over 12 million targets, covering 14,000 square degrees of the sky, with redshifts in the range 0.2< z < 1.35. We identify Galactic extinction, survey depth, and astronomical seeing as the primary sources of systematic error, and employ linear regression and artificial neural networks to alleviate non-cosmological excess clustering on large scales. Our methods are tested against log-normal simulations with and without fNL and systematics, showing superior performance of the neural network treatment in reducing remaining systematics. Assuming the universality relation, we find fNL $= 47^{+14(+29)}_{-11(-22)}$ at 68\%(95\%) confidence. With a more aggressive treatment, including regression against the full set of imaging maps, our maximum likelihood value shifts slightly to fNL$\sim 50$ and the uncertainty on fNL increases due to the removal of large-scale clustering information. We apply a series of robustness tests (e.g., cuts on imaging, declination, or scales used) that show consistency in the obtained constraints. Despite extensive efforts to mitigate systematics, our measurements indicate fNL > 0 with a 99.9 percent confidence level. This outcome raises concerns as it could be attributed to unforeseen systematics, including calibration errors or uncertainties associated with low-\ell systematics in the extinction template. Alternatively, it could suggest a scale-dependent fNL model--causing significant non-Gaussianity around large-scale structure while leaving cosmic microwave background scales unaffected. Our results encourage further studies of fNL with DESI spectroscopic samples, where the inclusion of 3D clustering modes should help separate imaging systematics.Comment: 19 pages, 15 figures, 6 tables (Appendix excluded). Submitted to MNRA

Subsequent Surgery After Revision Anterior Cruciate Ligament Reconstruction: Rates and Risk Factors From a Multicenter Cohort

BACKGROUND: While revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR. PURPOSE: To report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation. RESULTS: Of the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate. CONCLUSION: There was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms