Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17

Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size λ(sib) > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies

Characterization of variable EST SSR markers for Norway spruce (Picea abies L.)

<p>Abstract</p> <p>Background</p> <p>Norway spruce is widely distributed across Europe and the predominant tree of the Alpine region. Fast growth and the fact that timber can be harvested cost-effectively in relatively young populations define its status as one of the economically most important tree species of Northern Europe. In this study, EST derived simple sequence repeat (SSR) markers were developed for the assessment of putative functional diversity in Austrian Norway spruce stands.</p> <p>Results</p> <p>SSR sequences were identified by analyzing 14,022 publicly available EST sequences. Tri-nucleotide repeat motifs were most abundant in the data set followed by penta- and hexa-nucleotide repeats. Specific primer pairs were designed for sixty loci. Among these, 27 displayed polymorphism in a testing population of 16 <it>P. abies </it>individuals sampled across Austria and in an additional screening population of 96 <it>P. abies </it>individuals from two geographically distinct Austrian populations. Allele numbers per locus ranged from two to 17 with observed heterozygosity ranging from 0.075 to 0.99.</p> <p>Conclusions</p> <p>We have characterized variable EST SSR markers for Norway spruce detected in expressed genes. Due to their moderate to high degree of variability in the two tested screening populations, these newly developed SSR markers are well suited for the analysis of stress related functional variation present in Norway spruce populations.</p

Genic Microsatellite Markers in Brassica rapa: Development, Characterization, Mapping, and Their Utility in Other Cultivated and Wild Brassica Relatives

Genic microsatellite markers, also known as functional markers, are preferred over anonymous markers as they reveal the variation in transcribed genes among individuals. In this study, we developed a total of 707 expressed sequence tag-derived simple sequence repeat markers (EST-SSRs) and used for development of a high-density integrated map using four individual mapping populations of B. rapa. This map contains a total of 1426 markers, consisting of 306 EST-SSRs, 153 intron polymorphic markers, 395 bacterial artificial chromosome-derived SSRs (BAC-SSRs), and 572 public SSRs and other markers covering a total distance of 1245.9 cM of the B. rapa genome. Analysis of allelic diversity in 24 B. rapa germplasm using 234 mapped EST-SSR markers showed amplification of 2 alleles by majority of EST-SSRs, although amplification of alleles ranging from 2 to 8 was found. Transferability analysis of 167 EST-SSRs in 35 species belonging to cultivated and wild brassica relatives showed 42.51% (Sysimprium leteum) to 100% (B. carinata, B. juncea, and B. napus) amplification. Our newly developed EST-SSRs and high-density linkage map based on highly transferable genic markers would facilitate the molecular mapping of quantitative trait loci and the positional cloning of specific genes, in addition to marker-assisted selection and comparative genomic studies of B. rapa with other related species

Neuronal networks provide rapid neuroprotection against spreading toxicity

Acute secondary neuronal cell death, as seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI), drives spreading neurotoxicity into surrounding, undamaged, brain areas. This spreading toxicity occurs via two mechanisms, synaptic toxicity through hyperactivity, and excitotoxicity following the accumulation of extracellular glutamate. To date, there are no fast-acting therapeutic tools capable of terminating secondary spreading toxicity within a time frame relevant to the emergency treatment of stroke or TBI patients. Here, using hippocampal neurons (DIV 15-20) cultured in microfluidic devices in order to deliver a localized excitotoxic insult, we replicate secondary spreading toxicity and demonstrate that this process is driven by GluN2B receptors. In addition to the modeling of spreading toxicity, this approach has uncovered a previously unknown, fast acting, GluN2A-dependent neuroprotective signaling mechanism. This mechanism utilizes the innate capacity of surrounding neuronal networks to provide protection against both forms of spreading neuronal toxicity, synaptic hyperactivity and direct glutamate excitotoxicity. Importantly, network neuroprotection against spreading toxicity can be effectively stimulated after an excitotoxic insult has been delivered, and may identify a new therapeutic window to limit brain damage

Representativeness of microsatellite distributions in genomes, as revealed by 454 GS-FLX Titanium pyrosequencing

<p>Abstract</p> <p>Background</p> <p>Microsatellites are markers of choice in population genetics and genomics, as they provide useful insight into patterns and processes as diverse as genome evolutionary dynamics and demographic processes. The acquisition of microsatellites through multiplex-enriched libraries and 454 GS-FLX Titanium pyrosequencing is a promising new tool for the isolation of new markers in unknown genomes. This approach can also be used to evaluate the extent to which microsatellite-enriched libraries are representative of the genome from which they were isolated. In this study, we deciphered potential discrepancies in microsatellite content recovery for two reference genomes (<it>Apis mellifera </it>and <it>Danio rerio</it>), selected on the basis of their extreme heterogeneity in terms of the proportions and distributions of microsatellites on chromosomes.</p> <p>Results</p> <p>The <it>A. mellifera </it>genome, in particular, was found to be highly heterogeneous, due to extremely high rates of recombination, with hotspots, but the only bias consistently introduced into pyrosequenced multiplex-enriched libraries concerned sequence length, with the overrepresentation of sequences 160 to 320 bp in length. Other deviations from expected proportions or distributions of motifs on chromosomes were observed, but the significance and intensity of these deviations was mostly limited. Furthermore, no consistent adverse competition between multiplexed probes was observed during the motif enrichment phase.</p> <p>Conclusions</p> <p>This approach therefore appears to be a promising strategy for improving the development of microsatellites, as it introduces no major bias in terms of the proportions and distribution of microsatellites.</p

Intergenomic Rearrangements after Polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae) Affected by Environmental Factors

Polyploidization is a major evolutionary process. Approximately 70–75% species of Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al. (2n = 6x = 42, StStPPYY), collected from different environments, were studied using genome in situ hybridization (GISH). We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05). The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution

Relationships among the A Genomes of Triticum L. Species as Evidenced by SSR Markers, in Iran

The relationships among 55 wheat accessions (47 accessions collected from Iran and eight accessions provided by the Institute of Plant Biology of the University of Zurich, Switzerland) belonging to eight species carrying A genome (Triticum monococcum L., T. boeoticum Boiss., T. urartu Tumanian ex Gandilyan, T. durum Desf., T. turgidum L., T. dicoccum Schrank ex Schübler, T. dicoccoides (Körn. ex Asch. & Graebner) Schweinf. and T. aestivum L.) were evaluated using 31 A genome specific microsatellite markers. A high level of polymorphism was observed among the accessions studied (PIC = 0.77). The highest gene diversity was revealed among T. durum genotypes, while the lowest genetic variation was found in T. dicoccoides accessions. The analysis of molecular variance (AMOVA) showed a significant genetic variance (75.56%) among these accessions, representing a high intra-specific genetic diversity within Triticum taxa in Iran. However, such a variance was not observed among their ploidy levels. Based on the genetic similarity analysis, the accessions collected from Iran were divided into two main groups: diploids and polyploids. The genetic similarity among the diploid and polyploid species was 0.85 and 0.89 respectively. There were no significant differences in A genome diversity from different geographic regions. Based on the genetic diversity analyses, we consider there is value in a greater sampling of each species in Iran to discover useful genes for breeding purposes