Detection of Parent-of-Origin Specific Expression Quantitative Trait Loci by Cis-Association Analysis of Gene Expression in Trios
PLOS ONE
Authors: Garg, Paras; Borel, Christelle; Sharp, Andrew J.
Abstract
Parent-of-origin (PofO) effects, such as imprinting are a phenomenon in which homologous chromosomes exhibit differential gene expression and epigenetic modifications according to their parental origin. Such non-Mendelian inheritance patterns are generally ignored by conventional association studies, as these tests consider the maternal and paternal alleles as equivalent. To identify regulatory regions that show PofO effects on gene expression (imprinted expression Quantitative Trait Loci, ieQTLs), here we have developed a novel method in which we associate SNP genotypes of defined parental origin with gene expression levels. We applied this method to study 59 HapMap phase II parent-offspring trios. By analyzing mother/father/child trios, rules of Mendelian inheritance allowed the parental origin to be defined for similar to 95% of SNPs in each child. We used 680,475 informative SNPs and corresponding expression data for 92,167 probe sets from Affymetrix GeneChip Human Exon 1.0 ST arrays and performed four independent cis-association analyses with the expression level of RefSeq genes within 1 Mb using PLINK. Independent analyses of maternal and paternal genotypes identified two significant cis-ieQTLs (p<10(-7)) at which expression of genes SFT2D2 and SRRT associated exclusively with maternally inherited SNPs rs3753292 and rs6945374, respectively. 28 additional suggestive cis-associations with only maternal or paternal SNPs were found at a lower stringency threshold of p<10(-6), including associations with two known imprinted genes PEG10 and TRAPPC9, demonstrating the efficacy of our method. Furthermore, comparison of our method that utilizes independent analyses of maternal and paternal genotypes with the Likelihood Ratio Test (LRT) showed it to be more effective for detecting imprinting effects than the LRT. Our method represents a novel approach that can identify imprinted regulatory elements that control gene expression, suggesting novel PofO effects in the human genome.
Stress exponent and primary creep parameters using single specimen and strain relaxation and recovery test
MATERIALS SCIENCE AND ENGINEERING A-STRUCTURAL MATERIALS PROPERTIES MICROSTRUCTURE AND PROCESSING
Authors: Sinha, Nirmal K.
Abstract
Strain relaxation and recovery test (SRRT), requiring one specimen and viscous (permanent) strain, epsilon(v) (<= 0.001 per test) on full unloading during primary creep, is presented with results on gas-turbine engine materials: Ti-6246 at 600 degrees C, Discaloy at 500 degrees C, IN-738LC at 850 degrees C and Waspaloy at 732 degrees C. It is shown that a 'steady-state' in irreversible viscous flow develops during primary creep: the shape of the creep curve is controlled by time-dependent reversible delayed elastic (anelastic) response. The average viscous strain rate during primary-creep, (epsilon) over dot(v(av))(= epsilon(v)/t(SR)) for load duration, t(SR) and corresponding epsilon(v) can be used for the determination of the stress exponent, n(v) for viscous flow. It is shown that the value of n(v) for primary-creep is comparable to the stress exponent, n(min) for minimum creep rate. Using a single specimen, SRRTs also allow determinations of Young's modulus, stress exponent, s for delayed-elasticity (anelasticity), about one-third to fourth of n(v) and other parameters for the constitutive equation for primary creep-strictly before creep enhancement due to the onset of microcracking activities. Short-term and long-term SRRT data on Waspaloy indicated that the creep strain at minimum creep rate consists of a significant amount of recoverable strain (32% at 450 MPa and 38% at 650 MPa). Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.