Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Histopathologic Prognostic Factors in Stage I Leiomyosarcoma of the Uterus: A Detailed Analysis of 27 Cases.

Uterine leiomyosarcomas (Ut-LMSs) are aggressive tumors with an overall poor prognosis (15% to 25% 5-year survival rate). However, patients with stage I Ut-LMSs are reported to have a relatively better outcome when compared with the overall group with a 5-year survival rate ranging from 25% to 75%. The purpose of this study was to evaluate the histopathologic parameters that may impact outcome in stage I Ut-LMSs. Twenty-seven patients with stage I Ut-LMSs were identified from the files of 5 tertiary care hospitals between 1974 and 2006. Tumors were primarily staged based on pathologic information, supplemented with radiologic findings (10 cases) and clinical records (1 case). Patients with stage I tumors with no additional clinical or radiologic staging information were included in the study if no recurrence was documented after 6 months from the initial staging operation (16 cases). Clinicopathologic parameters that were statistically evaluated included age [mean, 54 y (37 to 73)], tumor size [mean, 9.5 cm (5.5 to 16)], cell type (17 spindled, 5 epithelioid, 2 myxoid, and 3 mixed), mitotic activity [mean count, 24 (4 to 69)/10 high-power fields], marked cytologic atypia (26 of 27 cases), tumor cell necrosis (12 of 27 cases), and lymphovascular invasion (6 of 27 cases). Follow-up was available for all the patients. Poor outcome was defined when patients either died of disease or were alive with disease. Overall, accounting for any length of follow-up, 16 of 27 (59%) patients with stage I Ut-LMSs had poor outcome; 7 died of disease (mean follow-up, 13 mo) and 9 were alive with disease (mean follow-up, 31 mo). The remaining 11 patients were alive and well with a mean follow-up of 48 months. However, at 2 years of follow-up by univariate analysis, only nonspindle morphology (