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Search: authors:"Eric J. Vallender"

16 papers found.
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Bringing non-human primate research into the post-genomic era: how monkeys are teaching us about elite controllers of HIV/AIDS

Whole-genome sequencing of Mauritian cynomolgus macaques reveals novel candidate loci for controlling simian immunodeficiency virus replication. See related Research, http://genomebiology.com/2014/15/11/478

Genetic substructure in cynomolgus macaques (Macaca fascicularis) on the island of Mauritius

Background Nonhuman primates are commonly used in biomedical research as animal models of human disease and behavior. Compared to common rodent models, nonhuman primates are genetically, physiologically, behaviorally and neurologically more similar to humans owing to more recent shared ancestry and therefore provide the advantage of greater translational validity in preclinical...

Expanding whole exome resequencing into non-human primates

Background Complete exome resequencing has the power to greatly expand our understanding of non-human primate genomes. This includes both a better appreciation of the variation that exists in non-human primate model species, but also an improved annotation of their genomes. By developing an understanding of the variation between individuals, non-human primate models of human...

Large-scale polymorphism discovery in macaque G-protein coupled receptors

Background G-protein coupled receptors (GPCRs) play an inordinately large role in human health. Variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. GPCRs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms. Recently, non...

Quantitative molecular assessment of chimerism across tissues in marmosets and tamarins

Vallender 0 0 New England Primate Research Center, Harvard Medical School , One Pine Hill Drive, Southborough, MA 01772 , USA Background: Marmosets are playing an increasingly large and important role in

Functional evolution of the trace amine associated receptors in mammals and the loss of TAAR1 in dogs

Background The trace amine associated receptor family is a diverse array of GPCRs that arose before the first vertebrates walked on land. Trace amine associated receptor 1 (TAAR1) is a wide spectrum aminergic receptor that acts as a modulator in brain monoaminergic systems. Other trace amine associated receptors appear to relate to environmental perception and show a birth-and...

Functional evolution of the trace amine associated receptors in mammals and the loss of TAAR1 in dogs

The trace amine associated receptor family is a diverse array of GPCRs that arose before the first vertebrates walked on land. Trace amine associated receptor 1 (TAAR1) is a wide spectrum aminergic receptor that acts as a modulator in brain monoaminergic systems. Other trace amine associated receptors appear to relate to environmental perception and show a birth-and-death pattern...

Uncovering the mutation-fixation correlation in short lineages

Background We recently reported a highly unexpected positive correlation between the fixation probability of nonsynonymous mutations (estimated by ω) and neutral mutation rate (estimated by Ks) in mammalian lineages. However, this positive correlation was observed for lineages with relatively long divergence time such as the human-mouse lineage, and was not found for very short...

A primate-specific acceleration in the evolution of the caspase-dependent apoptosis pathway

Programmed cell death, or apoptosis, plays an essential role in mammalian development, especially the development of the nervous system. Here, we systematically examine the molecular evolution of the mammalian intrinsic apoptosis program. We divided the program into its several constituent pathways and examined the evolution of each pathway in diverse mammalian taxa spanning...

Systematically Assessing the Influence of 3-Dimensional Structural Context on the Molecular Evolution of Mammalian Proteomes

The 3-dimensional (3D) structural context of amino acid residues in a protein could significantly impact the level of selective constraint on the residues. Here, by analyzing 767 mammalian proteins, we systematically investigate how various 3D structural contexts influence selective constraint. The structural contexts we examined include solvent accessibility, secondary structure...

Refinement of primate copy number variation hotspots identifies candidate genomic regions evolving under positive selection

Background Copy number variants (CNVs), defined as losses and gains of segments of genomic DNA, are a major source of genomic variation. Results In this study, we identified over 2,000 human CNVs that overlap with orthologous chimpanzee or orthologous macaque CNVs. Of these, 170 CNVs overlap with both chimpanzee and macaque CNVs, and these were collapsed into 34 hotspot regions...

SPEED: a molecular-evolution-based database of mammalian orthologous groups

Motivation: The abundance of nucleotide sequence information available has expanded horizons of inquiry for molecular evolution; however, the full potential of whole-genome analysis has not been realized because of inadequate tools. Here, we present one of the first toolkits to aid multidisciplinary high-throughput analysis. Summary: SPEED was created to integrate molecular...

Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies

Copy number variants (CNVs) are heritable gains and losses of genomic DNA in normal individuals. While copy number variation is widely studied in humans, our knowledge of CNVs in other mammalian species is more limited. We have designed a custom array-based comparative genomic hybridization (aCGH) platform with 385 000 oligonucleotide probes based on the reference genome sequence...

Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size

The defining process in the evolution of primates and particularly humans is the dramatic expansion of the brain. While many types of genes could potentially contribute to this process, genes that specifically regulate brain size during development may be especially relevant. Here, we examine the evolution of the microcephalin gene, whose null mutation in humans causes primary...

Sonic Hedgehog, a key development gene, experienced intensified molecular evolution in primates

Sonic Hedgehog (SHH) is one of the most intensively studied genes in developmental biology. It is a highly conserved gene, found in species as diverse as arthropods and mammals. The mammalian SHH encodes a signaling molecule that plays a central role in developmental patterning, especially of the nervous system and the skeletal system. Here, we show that the molecular evolution...

Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans

A prominent trend in the evolution of humans is the progressive enlargement of the cerebral cortex. The ASPM (Abnormal spindle-like microcephaly associated) gene has the potential to play a role in this evolu-tionary process, because mutations in this gene cause severe reductions in the cerebral cortical size of affected humans. Here, we show that the evolution of ASPM is...