Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with Ϸ90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up-and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity.

A fundamental step in the analysis of gene expression and other high-dimensional genomic data is the calculation of the similarity or distance between pairs of individual samples in a study. If one has collected N total samples and assayed the expression level of G genes on those samples, then an N ؋ N similarity matrix can be formed that reflects the correlation or similarity of the samples with respect to the expression values over the G genes. This matrix can then be examined for patterns via standard data reduction and cluster analysis techniques. We consider an alternative to conventional data reduction and cluster analyses of similarity matrices that is rooted in traditional linear models. This analysis method allows predictor variables collected on the samples to be related to variation in the pairwise similarity/distance values reflected in the matrix. The proposed multivariate method avoids the need for reducing the dimensions of a similarity matrix, can be used to assess relationships between the genes used to construct the matrix and additional information collected on the samples under study, and can be used to analyze individual genes or groups of genes identified in different ways. The technique can be used with any high-dimensional assay or data type and is ideally suited for testing subsets of genes defined by their participation in a biochemical pathway or other a priori grouping. We showcase the methodology using three published gene expression data sets.analysis of variance ͉ high-dimensional data

The current model to explain the organization of the mammalian nervous system is based on studies of anatomy, embryology, and evolution. To further investigate the molecular organization of the adult mammalian brain, we have built a gene expression-based brain map. We measured gene expression patterns for 24 neural tissues covering the mouse central nervous system and found, surprisingly, that the adult brain bears a transcriptional ''imprint'' consistent with both embryological origins and classic evolutionary relationships. Embryonic cellular position along the anteriorposterior axis of the neural tube was shown to be closely associated with, and possibly a determinant of, the gene expression patterns in adult structures. We also observed a significant number of embryonic patterning and homeobox genes with region-specific expression in the adult nervous system. The relationships between global expression patterns for different anatomical regions and the nature of the observed region-specific genes suggest that the adult brain retains a degree of overall gene expression established during embryogenesis that is important for regional specificity and the functional relationships between regions in the adult. The complete collection of extensively annotated gene expression data along with data mining and visualization tools have been made available on a publicly accessible web site (www.barlow-lockhartbrainmapnimhgrant.org).database ͉ development ͉ evolution ͉ gene expression profiling ͉ inbred strains of mice T he adult nervous system achieves its mature form as the result of neuroectodermal cells committing to a specific fate and then segregating into distinct regional collectives of neurons that become fully functional through establishment of connections to other neurons. Our current understanding of brain architecture and organization is based on studies of embryology, anatomy, and evolution in which direct observation of anatomic structures was the foundation for postulated models of brain structure (1). Recent models of brain development and maturation consider relationships between different regions based on the expression of specific genes in assigning developmental origins of adult structures (2, 3). Here, we have constructed a regional gene expression atlas of the adult mouse brain and analyzed the quantitative results by using molecular classification algorithms.Genome-wide gene expression profiling is a powerful technique for deriving information about specific brain regions (4, 5). This approach has been used to measure gene expression patterns in particular regions, subregions, or cell populations in the brain (6-11). Two previous studies have analyzed gene expression differences across multiple regions of the mammalian brain by using multiple strains or species (12,13). However, the current study is the most extensive to date in terms of the number of genes and the coverage of different neural tissues. Our goal was to create a publicly accessible gene-based brain map with data sets, metadata, datab...

Intussusception is a common etiology of acute abdominal pain in children. Over the last 70 years, there have been significant changes in how we diagnose and treat intussusception, with a more recent focus on the role of ultrasound. In this article we discuss historical and current approaches to intussusception, with an emphasis on ultrasound as a diagnostic and therapeutic modality.