Runs of homozygosity and testicular cancer risk

Background: Testicular germ cell tumour (TGCT) is highly heritable but > 50% of the genetic risk remains unexplained. Epidemiological observation of greater relative risk to brothers of men with TGCT compared to sons has long alluded to recessively acting TGCT genetic susceptibility factors, but to date none have been reported. Runs of homozygosity (RoH) are a signature indicating underlying recessively acting alleles and have been associated with increased risk of other cancer types. / Objective: To examine whether RoH are associated with TGCT risk. / Methods: We performed a genome‐wide RoH analysis using GWAS data from 3206 TGCT cases and 7422 controls uniformly genotyped using the OncoArray platform. / Results: Global measures of homozygosity were not significantly different between cases and controls, and the frequency of individual consensus RoH was not significantly different between cases and controls, after correction for multiple testing. RoH at three regions, 11p13‐11p14.3, 5q14.1‐5q22.3 and 13q14.11‐13q.14.13, were, however, nominally statistically significant at p < 0.01. Intriguingly, RoH200 at 11p13‐11p14.3 encompasses Wilms tumour 1 (WT1), a recognized cancer susceptibility gene with roles in sex determination and developmental transcriptional regulation, processes repeatedly implicated in TGCT aetiology. / Discussion and conclusion: Overall, our data do not support a major role in the risk of TGCT for recessively acting alleles acting through homozygosity, as measured by RoH in outbred populations of cases and controls

Creep Behavior of an Al-2.0 Wt Pct Li Alloy in the Temperature Range 300 °C to 500 °C

The elevated temperature deformation behavior of an Al-2. 0 wt pct Li alloy in the temperature range 300 °C to 500 °C was studied using constant extension-rate tension testing and constant true-stress creep testing under both isothermal and temperature cycling conditions. Optical microscopy and transmission electron microscopy (TEM) were employed to assess the effect of deformation on microstructure. The data showed that the stress exponent,n, has a value of about 5. 0 at temperatures above theα +δAlLi solvus (approximately 380 °C) and that subgrains form during plastic deformation. Models for dislocation-climb and dislocation-glide control of creep were analyzed for alloys deformed in the temperature range of stability of the terminal AlLi solid solution. A climb model was shown to describe closely the behavior of this material. Anomalous temperature dependence of the activation energy was observed in this same temperature range. This anomalous behavior was ascribed to unusual temperature dependence of either the Young’s modulus or the stacking fault energy, which may be associated, in turn, with a disorder-order transformation on cooling of the alloy.Naval Postgraduate SchoolNaval Surface Weapons Cente