Electrophysiological Investigation Of Amygdaloid Inputs To The Ventral Pallidum Via The Nucleus Accumbens And Their Modulation By Dopamine

The nucleus accumbens (NA) receives inputs from limbic structures and projects to the basal ganglia. In addition, it is the target of a heavy dopaminergic projection from the ventral tegmental area (VTA). The purpose of the present study is to investigate using electrophysiological techniques whether or not the NA forms a functional link between the amygdala (AMY) and the ventral pallidum (VP), and whether or not the mesolimbic dopamine projection from the VTA interacts with this pathway.;Electrical stimulation of the basolateral nucleus of the AMY caused an excitation was attenuated by ionotophoretically applied dopamine (DA) or electrical stimulation of the VTA at 10 Hz for 1 s (VTA conditioning stimulation) prior to stimulation of the AMY. The attenuating effect of VTA conditioning stimulation was abolished by acute intraperitoneal injection of haloperidol, a DA antagonist, and was not observed in rats in which the mesolimbic DA projection had been lesioned by 6-hydroxydopamine.;Electrical stimulation of the AMY produced predominantly inhibitory responses in the VP. The onset latencies of the inhibitory responses showed a bimodal distribution suggesting that the responses could be elicited via two pathways. Those with long onset latencies (\u3e 12 ms) were likely mediated via the NA since microinjection of procaine HCl or d-amphetamine into the NA abolished these responses. VTA conditioning stimulation also produced an attenuating effect on the long latency inhibitory responses in normal rats but not in rats with 6-OHDA lesions in the VTA. Inhibitory responses with short onset latencies (\u3c = 12 ms) were not affected by any of these treatments.;These results suggest that the NA forms a connecting link between the AMY and the VP thus allowing output from the AMY to influence activity of neurons in the VP. Activity of the mesolimbic DA projection to the NA modulates the response of NA neurons to AMY input and thus the AMY\u27s influence on the VP. Since the VP projects to motor areas of the brain, it is suggested that the AMY to NA to VP pathway may be a connecting link between the limbic and motor systems. The mesolimbic DA projection to the NA may serve as a gate to modulate output from limbic structures to the motor systems via this pathway

Copy number variations in East-Asian population and their evolutionary and functional implications

Recent discovery of the copy number variation (CNV) in normal individuals has widened our understanding of genomic variation. However, most of the reported CNVs have been identified in Caucasians, which may not be directly applicable to people of different ethnicities. To profile CNV in East-Asian population, we screened CNVs in 3578 healthy, unrelated Korean individuals, using the Affymetrix Genome-Wide Human SNP array 5.0. We identified 144 207 CNVs using a pooled data set of 100 randomly chosen Korean females as a reference. The average number of CNVs per genome was 40.3, which is higher than that of CNVs previously reported using lower resolution platforms. The median size of CNVs was 18.9 kb (range 0.2–5406 kb). Copy number losses were 4.7 times more frequent than copy number gains. CNV regions (CNVRs) were defined by merging overlapping CNVs identified in two or more samples. In total, 4003 CNVRs were defined encompassing 241.9 Mb accounting for ∼8% of the human genome. A total of 2077 CNVRs (51.9%) were potentially novel. Known CNVRs were larger and more frequent than novel CNVRs. Sixteen percent of the CNVRs were observed in ≥1% of study subjects and 24% overlapped with the OMIM genes. A total of 476 (11.9%) CNVRs were associated with segmental duplications. CNVS/CNVRs identified in this study will be valuable resources for studying human genome diversity and its association with disease

High mutation rates explain low population genetic divergence at copy-number-variable loci in Homo sapiens

Copy-number-variable (CNV) loci differ from single nucleotide polymorphic (SNP) sites in size, mutation rate, and mechanisms of maintenance in natural populations. It is therefore hypothesized that population genetic divergence at CNV loci will differ from that found at SNP sites. Here, we test this hypothesis by analysing 856 CNV loci from the genomes of 1184 healthy individuals from 11 HapMap populations with a wide range of ancestry. The results show that population genetic divergence at the CNV loci is generally more than three times lower than at genome-wide SNP sites. Populations generally exhibit very small genetic divergence (G(st) = 0.05 ± 0.049). The smallest divergence is among African populations (G(st) = 0.0081 ± 0.0025), with increased divergence among non-African populations (G(st) = 0.0217 ± 0.0109) and then among African and non-African populations (G(st) = 0.0324 ± 0.0064). Genetic diversity is high in African populations (~0.13), low in Asian populations (~0.11), and intermediate in the remaining 11 populations. Few significant linkage disequilibria (LDs) occur between the genome-wide CNV loci. Patterns of gametic and zygotic LDs indicate the absence of epistasis among CNV loci. Mutation rate is about twice as large as the migration rate in the non-African populations, suggesting that the high mutation rates play dominant roles in producing the low population genetic divergence at CNV loci

An initial comparative map of copy number variations in the goat (Capra hircus) genome

<p>Abstract</p> <p>Background</p> <p>The goat (<it>Capra hircus</it>) represents one of the most important farm animal species. It is reared in all continents with an estimated world population of about 800 million of animals. Despite its importance, studies on the goat genome are still in their infancy compared to those in other farm animal species. Comparative mapping between cattle and goat showed only a few rearrangements in agreement with the similarity of chromosome banding. We carried out a cross species cattle-goat array comparative genome hybridization (aCGH) experiment in order to identify copy number variations (CNVs) in the goat genome analysing animals of different breeds (Saanen, Camosciata delle Alpi, Girgentana, and Murciano-Granadina) using a tiling oligonucleotide array with ~385,000 probes designed on the bovine genome.</p> <p>Results</p> <p>We identified a total of 161 CNVs (an average of 17.9 CNVs per goat), with the largest number in the Saanen breed and the lowest in the Camosciata delle Alpi goat. By aggregating overlapping CNVs identified in different animals we determined CNV regions (CNVRs): on the whole, we identified 127 CNVRs covering about 11.47 Mb of the virtual goat genome referred to the bovine genome (0.435% of the latter genome). These 127 CNVRs included 86 loss and 41 gain and ranged from about 24 kb to about 1.07 Mb with a mean and median equal to 90,292 bp and 49,530 bp, respectively. To evaluate whether the identified goat CNVRs overlap with those reported in the cattle genome, we compared our results with those obtained in four independent cattle experiments. Overlapping between goat and cattle CNVRs was highly significant (P < 0.0001) suggesting that several chromosome regions might contain recurrent interspecies CNVRs. Genes with environmental functions were over-represented in goat CNVRs as reported in other mammals.</p> <p>Conclusions</p> <p>We describe a first map of goat CNVRs. This provides information on a comparative basis with the cattle genome by identifying putative recurrent interspecies CNVs between these two ruminant species. Several goat CNVs affect genes with important biological functions. Further studies are needed to evaluate the functional relevance of these CNVs and their effects on behavior, production, and disease resistance traits in goats.</p

SgD-CNV, a database for common and rare copy number variants in three Asian populations

10.1002/humu.21601Human Mutation32121341-1349HUMU

Genomic copy number variations in three southeast Asian populations

10.1002/humu.21287Human Mutation317851-85