Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees

A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants

Assembly of a pan-genome from deep sequencing of 910 humans of African descent

Host-parasite interactio

A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome

Host-parasite interactio

Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations (vol 10, 880, 2019)

Host-parasite interactio

Charm production and fragmentation fractions at midrapidity in pp collisions at √s = 13 TeV

Measurements of the production cross sections of prompt D0, D+, D∗+, D+s, Λ+c, and Ξ+c charm hadrons at midrapidity in proton−proton collisions at s√=13 TeV with the ALICE detector are presented. The D-meson cross sections as a function of transverse momentum (pT) are provided with improved precision and granularity. The ratios of pT-differential meson production cross sections based on this publication and on measurements at different rapidity and collision energy provide a constraint on gluon parton distribution functions at low values of Bjorken-x (10−5−10−4). The measurements of Λ+c (Ξ+c) baryon production extend the measured pT intervals down to pT=0(3)~GeV/c. These measurements are used to determine the charm-quark fragmentation fractions and the cc¯¯ production cross section at midrapidity (|y|<0.5) based on the sum of the cross sections of the weakly-decaying ground-state charm hadrons D0, D+, D+s, Λ+c, Ξ0c and, for the first time, Ξ+c, and of the strongly-decaying J/psi mesons. The first measurements of Ξ+c and Σ0,++c fragmentation fractions at midrapidity are also reported. A significantly larger fraction of charm quarks hadronising to baryons is found compared to e+e− and ep collisions. The cc¯¯ production cross section at midrapidity is found to be at the upper bound of state-of-the-art perturbative QCD calculations

Measurements of the groomed jet radius and momentum splitting fraction with the soft drop and dynamical grooming algorithms in pp collisions at √s = 5.02 TeV

This article presents measurements of the groomed jet radius and momentum splitting fraction in pp collisions at s√=5.02 TeV with the ALICE detector at the Large Hadron Collider. Inclusive charged-particle jets are reconstructed at midrapidity using the anti-kT algorithm for transverse momentum 60<pchjetT<80 GeV/c. We report results using two different grooming algorithms: soft drop and, for the first time, dynamical grooming. For each grooming algorithm, a variety of grooming settings are used in order to explore the impact of collinear radiation on these jet substructure observables. These results are compared to perturbative calculations that include resummation of large logarithms at all orders in the strong coupling constant. We find good agreement of the theoretical predictions with the data for all grooming settings considered