Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population

<div><p>Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0–17.6, p-value < 2.0E-07), comprised of seven coding variants in genes <i>RAB11FIP5</i>, <i>POTEA</i>, <i>COL27A1</i>, <i>MUC5B</i>, <i>PSMA8</i>, <i>MYH7B</i>, and <i>PABPC1L</i> as well as one variant downstream of <i>NEU1</i> gene. We also confirmed 27 out of 30 risk variants previously reported from GWAS in CRC with a mixed European population background. This study identified rare, coding sequence variants associated with CRC risk through analysis in a relatively homogeneous population. The segregation data suggest a complex mode of inheritance in seemingly dominant pedigrees.</p></div

A proteomic insight into the midgut proteome of Ornithodoros moubata females reveals novel information on blood digestion in argasid ticks

[Background]: The argasid tick Ornithodoros moubata is the main African vector of the human relapsing fever agent Borrelia duttoni and the African swine fever virus. Together with saliva, the tick midgut forms part of the host-tick-pathogen interface, and numerous midgut proteins play key functions in the blood digestion-related process and the infection and transmission of pathogens. This work explores the composition of the midgut proteome of unfed and fed O. moubata females with the aim to complete the biological information already obtained from the midgut transcriptome and provide a more robust and comprehensive perspective of this biological system.[Methods]: Midgut tissues taken from females before feeding and 48 h after feeding were subjected to LC/MS-MS analysis. After functional characterization and classification of the proteins identified, the differences in the proteome between unfed and fed females were analysed and discussed. Additionally, a detailed analysis of particular groups of proteins that are involved in the processes of nutrient digestion and responses to the oxidative stress was carried out.[Results]: 1491 non-redundant tick proteins were identified: 1132 of them in the midgut of unfed ticks, 1138 in the midgut of fed ticks, and up to 779 shared by both physiological conditions. Overall, the comparative analysis of the midgut proteomes of O. moubata females before and after feeding did not reveal great differences in the number or class of proteins expressed, enzymatic composition or functional classification.[Conclusions]: The hemoglobinolytic system in ixodids and argasids is very similar in spite of the fact that they display very different feeding and reproductive strategies. Although the main source of nutrients in ticks are proteins, lipids and carbohydrates also constitute significant nutritional sources and play an important part in the process of blood digestion. The genes and proteins involved in intracellular transport mechanisms, defensive responses, detoxifying responses and stress responses seem to be closely regulated, highlighting the complexity and importance of these processes in tick biology, which in turn assigns them a great interest as targets for therapeutic and immunological interventions.We acknowledge the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).This research was funded by project AGL2013–42745-P granted by the Spanish Ministry of Economy and Competitiveness.Peer reviewe

Distinguishing Amorphous and Crystalline Ice by Ultralow Energy Collisions of Reactive Ions

Ion scattering using ultralow energy projectiles is considered to be a unique method to probe the nature of molecular surfaces because of its capacity to probe the very top, atomically thin layers. Here, we examine one of the most studied molecular solids, water-ice, using this technique. When ice surface undergoes the amorphous to crystalline transition, an ultralow energy reactive projectile identifies the change through the reaction product formed. It is shown that ultralow energy (2, 3, 4, 5, 6, and 7 eV) CH₂⁺ (or CD₂⁺) collision on amorphous D₂O (or H₂O) ice makes CHD⁺, while crystalline ice does not. The projectile undergoes H/D exchange with the dangling −OD (−OH) bond present on amorphous ice surfaces. It is also shown that H/D exchange product disappears when amorphous ice is annealed to the crystalline phase. The H/D exchange reaction is shown to be sensitive only to the surface layers of ice as it disappears when the surface is covered with long chain alcohols like 1-pentanol as the ice surfaces become inaccessible for the incoming projectile. This article shows that ultralow energy reactive ion collision is a novel method to distinguish phase transitions in molecular solids