Visualizing Chromosome Mosaicism and Detecting Ethnic Outliers by the Method of “Rare” Heterozygotes and Homozygotes (RHH)

We describe a novel approach for evaluating SNP genotypes of a genome-wide association scan to identify “ethnic outlier” subjects whose ethnicity is different or admixed compared to most other subjects in the genotyped sample set. Each ethnic outlier is detected by counting a genomic excess of “rare” heterozygotes and/or homozygotes whose frequencies are low (<1%) within genotypes of the sample set being evaluated. This method also enables simple and striking visualization of non-Caucasian chromosomal DNA segments interspersed within the chromosomes of ethnically admixed individuals. We show that this visualization of the mosaic structure of admixed human chromosomes gives results similar to another visualization method (SABER) but with much less computational time and burden. We also show that other methods for detecting ethnic outliers are enhanced by evaluating only genomic regions of visualized admixture rather than diluting outlier ancestry by evaluating the entire genome considered in aggregate. We have validated our method in the Wellcome Trust Case Control Consortium (WTCCC) study of 17,000 subjects as well as in HapMap subjects and simulated outliers of known ethnicity and admixture. The method's ability to precisely delineate chromosomal segments of non-Caucasian ethnicity has enabled us to demonstrate previously unreported non-Caucasian admixture in two HapMap Caucasian parents and in a number of WTCCC subjects. Its sensitive detection of ethnic outliers and simple visual discrimination of discrete chromosomal segments of different ethnicity implies that this method of rare heterozygotes and homozygotes (RHH) is likely to have diverse and important applications in humans and other species

Trifold Advertisement for Quotations from Abraham Lincoln by Ralph Y. McGinnis

This is a trifold advertisement from Nelson-Hall Publishers, Chicago, for Quotations from Abraham Lincoln by Ralph Y. McGinnis. The front of the advertisement features an oval shaped portrait of Abraham Lincoln.https://scholarsjunction.msstate.edu/fvw-artifacts/5652/thumbnail.jp

Microwave Schottky diagnostic systems for the Fermilab Tevatron, Recycler, and CERN LHC

A means for non-invasive measurement of transverse and longitudinal characteristics of bunched beams in synchrotrons has been developed based on high sensitivity slotted waveguide pickups. The pickups allow for bandwidths exceeding hundreds of MHz while maintaining good beam sensitivity characteristics. Wide bandwidth is essential to allow bunch-by-bunch measurements by means of a fast gate. The Schottky detector system is installed and successfully commissioned in the Fermilab Tevatron, Recycler and CERN LHC synchrotrons. Measurement capabilities include tune, chromaticity, and momentum spread of single or multiple beam bunches in any combination. With appropriate calibrations, emittance can also be measured by integrating the area under the incoherent tune sidebands

Debuncher cooling performance

We present measurements of the Fermilab Debuncher momentum and transverse cooling systems. These systems use liquid helium cooled waveguide pickups and slotted waveguide kickers covering the frequency range 4-8 GHz

Debuncher Cooling Performance

Abstract. We present measurements of the Fermilab Debuncher momentum and transverse cooling systems. These systems use liquid helium cooled waveguide pickups and slotted waveguide kickers covering the frequency range 4-8 GHz. Keywords: Stochastic Cooling, Antiproton Beams PACS: 41.75.Lx THE FERMILAB DEBUNCHER The Fermilab Debuncher is an 8 GeV ring designed for the collection, RF debunching, and storage of anitprotons. The Tevatron Collider program requires 1e13 antiprotons for the study of proton-antiproton collisions at √ s = 1.96 TeV. Antiprotons are produced by impinging a 120 GeV proton beam on an nickel alloy target and collected through a lithium focussing lens and the Debuncher ring then stochastic stacked in the Fermilab Accumulator PERFORMANCE REQUIREMENTS The Debuncher accepts a few ×10 8 antiprotons every 2 seconds. The input beam fills the transverse aperture of the beam, consistent with a transverse emittance of 320π mm mr (95% unnormalized). At the end of the 2 second cycle, the beam is required to have transverse emittance less than 45π mm mr (95% unnormalized) in both planes (factor of 7). After bunch rotation, the 95% momentum width is approximately 60 MeV/c. At the end of the 2 second cycle, the 95% momentum width of the beam is required to be less than 6 MeV/c (factor of 10). These requirements correspond to a 6-dimensional phase space density (ρ 6d = N particles ε l ε h ε v ) increase of a factor of 500

Performance and upgrades of the Fermilab Accumulator stacktail stochastic cooling

We report on the performance and planned upgrades to the Fermilab Accumulator Stacktail Stochastic Cooling System. The current system has achieved a maximum flux of 16.5e10/hour, limited by the input flux of antiprotons. The upgrades are designed to handle flux in excess of 40e10/hour

Interactions among genes in the ErbB-Neuregulin signalling network are associated with increased susceptibility to schizophrenia

<p>Abstract</p> <p>Background</p> <p>Evidence of genetic association between the NRG1 (Neuregulin-1) gene and schizophrenia is now well-documented. Furthermore, several recent reports suggest association between schizophrenia and single-nucleotide polymorphisms (SNPs) in ERBB4, one of the receptors for Neuregulin-1. In this study, we have extended the previously published associations by investigating the involvement of all eight genes from the ERBB and NRG families for association with schizophrenia.</p> <p>Methods</p> <p>Eight genes from the ERBB and NRG families were tested for association to schizophrenia using a collection of 396 cases and 1,342 blood bank controls ascertained from Aberdeen, UK. A total of 365 SNPs were tested. Association testing of both alleles and genotypes was carried out using the fast Fisher's Exact Test (FET). To understand better the nature of the associations, all pairs of SNPs separated by ≥ 0.5 cM with at least nominal evidence of association (<it>P </it>< 0.10) were tested for evidence of pairwise interaction by logistic regression analysis.</p> <p>Results</p> <p>42 out of 365 tested SNPs in the eight genes from the ERBB and NRG gene families were significantly associated with schizophrenia (<it>P </it>< 0.05). Associated SNPs were located in ERBB4 and NRG1, confirming earlier reports. However, novel associations were also seen in NRG2, NRG3 and EGFR. In pairwise interaction tests, clear evidence of gene-gene interaction was detected for NRG1-NRG2, NRG1-NRG3 and EGFR-NRG2, and suggestive evidence was also seen for ERBB4-NRG1, ERBB4-NRG2, ERBB4-NRG3 and ERBB4-ERBB2. Evidence of intragenic interaction was seen for SNPs in ERBB4.</p> <p>Conclusion</p> <p>These new findings suggest that observed associations between NRG1 and schizophrenia may be mediated through functional interaction not just with ERBB4, but with other members of the NRG and ERBB families. There is evidence that genetic interaction among these loci may increase susceptibility to schizophrenia.</p

Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.

Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10-11) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes

Alternative Splicing and Nonsense-Mediated RNA Decay Contribute to the Regulation of SHOX Expression

The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During development, SHOX is expressed in a highly specific spatiotemporal expression pattern, the underlying regulatory mechanisms of which remain largely unknown. We have analysed SHOX expression in diverse embryonic, fetal and adult human tissues and detected expression in many tissues that were not known to express SHOX before, e.g. distinct brain regions. By using RT-PCR and comparing the results with RNA-Seq data, we have identified four novel exons (exon 2a, 7-1, 7-2 and 7-3) contributing to different SHOX isoforms, and also established an expression profile for the emerging new SHOX isoforms. Interestingly, we found the exon 7 variants to be exclusively expressed in fetal neural tissues, which could argue for a specific role of these variants during brain development. A bioinformatical analysis of the three novel 3′UTR exons yielded insights into the putative role of the different 3′UTRs as targets for miRNA binding. Functional analysis revealed that inclusion of exon 2a leads to nonsense-mediated RNA decay altering SHOX expression in a tissue and time specific manner. In conclusion, SHOX expression is regulated by different mechanisms and alternative splicing coupled with nonsense-mediated RNA decay constitutes a further component that can be used to fine tune the SHOX expression level