23 research outputs found
Magnetic Interactions and Transport in (Ga,Cr)As
The magnetic, transport, and structural properties of (Ga,Cr)As are reported.
Zincblende GaCrAs was grown by low-temperature molecular beam
epitaxy (MBE). At low concentrations, x0.1, the materials exhibit unusual
magnetic properties associated with the random magnetism of the alloy. At low
temperatures the magnetization M(B) increases rapidly with increasing field due
to the alignment of ferromagnetic units (polarons or clusters) having large
dipole moments of order 10-10. A standard model of
superparamagnetism is inadequate for describing both the field and temperature
dependence of the magnetization M(B,T). In order to explain M(B) at low
temperatures we employ a distributed magnetic moment (DMM) model in which
polarons or clusters of ions have a distribution of moments. It is also found
that the magnetic susceptibility increases for decreasing temperature but
saturates below T=4 K. The inverse susceptibility follows a linear-T
Curie-Weiss law and extrapolates to a magnetic transition temperature
=10 K. In magnetotransport measurements, a room temperature resistivity
of =0.1 cm and a hole concentration of cm
are found, indicating that Cr can also act as a acceptor similar to Mn. The
resistivity increases rapidly for decreasing temperature below room
temperature, and becomes strongly insulating at low temperatures. The
conductivity follows exp[-(T/T)] over a large range of
conductivity, possible evidence of tunneling between polarons or clusters.Comment: To appear in PRB 15 Mar 200
Boundary work: becoming middle class in suburban Dar es Salaam
Suburban space provides a useful window onto contemporary class practices in Africa, where it is difficult to identify social classes on the basis of income or occupation. In this article I argue that the middle classes and the suburbs are mutually constitutive in the Tanzanian city of Dar es Salaam. Using interviews with residents and local government officials in the city's northern suburbs, I discuss the material and representational practices of middle-class boundary work in relation to land and landscape. If the middle classes do not presently constitute a coherent political-economic force, they are nevertheless transforming the city's former northern peri-urban zones into desirable suburban residential neighbourhoods
De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.
We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk
Synaptic processes and immune-related pathways implicated in Tourette syndrome.
Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS
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Results Of A Genome-wide Genetic Screen For Panic Disorder
Panic disorder is characterized by spontaneous and recurrent panic attacks, often accompanied by agoraphobia. The results of family, twin, and segregation studies suggest a genetic role in the etiology of the illness. We have genotyped up to 23 families that have a high density of panic disorder with 540 microsatellite DNA markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing all the autosomes, at an average marker density of 11 cM. Over 110,000 genotypes have been generated on the whole set of families, and the data have been analyzed under both a dominant and a recessive model, and with the program SIBPAIR.
No lod scores exceed 2.0 for either parametric model. Two markers give lod scores over 1.0 under the dominant model (chromosomes 1p and 20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these (20p) may be particularly promising. Analysis with SIBPAIR yielded P values equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided, uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q, 16p, 20p and 20q)
Supplementary Material for: An Analytic Solution to the Computation of Power and Sample Size for Genetic Association Studies under a Pleiotropic Mode of Inheritance
<p>Our motivation here is to calculate the power of 3 statistical tests
used when there are genetic traits that operate under a pleiotropic mode
of inheritance and when qualitative phenotypes are defined by use of
thresholds for the multiple quantitative phenotypes. Specifically, we
formulate a multivariate function that provides the probability that an
individual has a vector of specific quantitative trait values
conditional on having a risk locus genotype, and we apply thresholds to
define qualitative phenotypes (affected, unaffected) and compute
penetrances and conditional genotype frequencies based on the
multivariate function. We extend the analytic power and
minimum-sample-size-necessary (MSSN) formulas for 2 categorical
data-based tests (genotype, linear trend test [LTT]) of genetic
association to the pleiotropic model. We further compare the MSSN of the
genotype test and the LTT with that of a multivariate ANOVA (Pillai).
We approximate the MSSN for statistics by linear models using a
factorial design and ANOVA. With ANOVA decomposition, we determine which
factors most significantly change the power/MSSN for all statistics.
Finally, we determine which test statistics have the smallest MSSN. In
this work, MSSN calculations are for 2 traits (bivariate distributions)
only (for illustrative purposes). We note that the calculations may be
extended to address any number of traits. Our key findings are that the
genotype test usually has lower MSSN requirements than the LTT. More
inclusive thresholds (top/bottom 25% vs. top/bottom 10%) have higher
sample size requirements. The Pillai test has a much larger MSSN than
both the genotype test and the LTT, as a result of sample selection.
With these formulas, researchers can specify how many subjects they must
collect to localize genes for pleiotropic phenotypes.</p
Investigation of gene-environment interactions in relation to tic severity.
Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies