Spin-Dependent Mass Enhancement under Magnetic Field in the Periodic Anderson Model

In order to study the mechanism of the mass enhancement in heavy fermion compounds in the presence of magnetic field, we study the periodic Anderson model using the fluctuation exchange approximation. The resulting value of the mass enhancement factor z^{-1} can become up to 10, which is significantly larger than that in the single-band Hubbard model. We show that the difference between the magnitude of the mass enhancement factor of up spin (minority spin) electrons z^{-1}_up and that of down spin (majority spin) electrons z^{-1}_down increases by the applied magnetic field B//z, which is consistent with de Haas-van Alphen measurements for CeCoIn_5, CeRu_2Si_2 and CePd_2Si_2. We predict that z^{-1}_up >z^{-1}_down in many Ce compounds, whereas z^{-1}_up < z^{-1}_down in Yb compounds.Comment: 5 pages, 4 figure

High-Resolution Copy-Number Variation Map Reflects Human Olfactory Receptor Diversity and Evolution

Olfactory receptors (ORs), which are involved in odorant recognition, form the largest mammalian protein superfamily. The genomic content of OR genes is considerably reduced in humans, as reflected by the relatively small repertoire size and the high fraction (∼55%) of human pseudogenes. Since several recent low-resolution surveys suggested that OR genomic loci are frequently affected by copy-number variants (CNVs), we hypothesized that CNVs may play an important role in the evolution of the human olfactory repertoire. We used high-resolution oligonucleotide tiling microarrays to detect CNVs across 851 OR gene and pseudogene loci. Examining genomic DNA from 25 individuals with ancestry from three populations, we identified 93 OR gene loci and 151 pseudogene loci affected by CNVs, generating a mosaic of OR dosages across persons. Our data suggest that ∼50% of the CNVs involve more than one OR, with the largest CNV spanning 11 loci. In contrast to earlier reports, we observe that CNVs are more frequent among OR pseudogenes than among intact genes, presumably due to both selective constraints and CNV formation biases. Furthermore, our results show an enrichment of CNVs among ORs with a close human paralog or lacking a one-to-one ortholog in chimpanzee. Interestingly, among the latter we observed an enrichment in CNV losses over gains, a finding potentially related to the known diminution of the human OR repertoire. Quantitative PCR experiments performed for 122 sampled ORs agreed well with the microarray results and uncovered 23 additional CNVs. Importantly, these experiments allowed us to uncover nine common deletion alleles that affect 15 OR genes and five pseudogenes. Comparison to the chimpanzee reference genome revealed that all of the deletion alleles are human derived, therefore indicating a profound effect of human-specific deletions on the individual OR gene content. Furthermore, these deletion alleles may be used in future genetic association studies of olfactory inter-individual differences

Integrating Sequencing Technologies in Personal Genomics: Optimal Low Cost Reconstruction of Structural Variants

The goal of human genome re-sequencing is obtaining an accurate assembly of an individual's genome. Recently, there has been great excitement in the development of many technologies for this (e.g. medium and short read sequencing from companies such as 454 and SOLiD, and high-density oligo-arrays from Affymetrix and NimbelGen), with even more expected to appear. The costs and sensitivities of these technologies differ considerably from each other. As an important goal of personal genomics is to reduce the cost of re-sequencing to an affordable point, it is worthwhile to consider optimally integrating technologies. Here, we build a simulation toolbox that will help us optimally combine different technologies for genome re-sequencing, especially in reconstructing large structural variants (SVs). SV reconstruction is considered the most challenging step in human genome re-sequencing. (It is sometimes even harder than de novo assembly of small genomes because of the duplications and repetitive sequences in the human genome.) To this end, we formulate canonical problems that are representative of issues in reconstruction and are of small enough scale to be computationally tractable and simulatable. Using semi-realistic simulations, we show how we can combine different technologies to optimally solve the assembly at low cost. With mapability maps, our simulations efficiently handle the inhomogeneous repeat-containing structure of the human genome and the computational complexity of practical assembly algorithms. They quantitatively show how combining different read lengths is more cost-effective than using one length, how an optimal mixed sequencing strategy for reconstructing large novel SVs usually also gives accurate detection of SNPs/indels, how paired-end reads can improve reconstruction efficiency, and how adding in arrays is more efficient than just sequencing for disentangling some complex SVs. Our strategy should facilitate the sequencing of human genomes at maximum accuracy and low cost

Respiratory syncytial virus as a cause of pulmonary hemorrhage in a low birth weight infant - strategies for protection and prevention: a case report

A case study of 39-year old man with persistent wheezing, episodes of haemoptysis and dry cough unsuccessfully treated with inhaled beta2-agonists and steroids for about 10 months. Chest radiograph revealed a disproportion in dimensions between both lungs, with the left one being smaller than the right one. Spirometry demonstrated a restrictive pattern. During bronchoscopy, a polypoid endobronchial tumor, localized in the left main bronchus, completely occluding its lumen, was found. The tumor was diagnosed as carcinoid. In this case, due to the lack of characteristic symptoms, diagnosis of carcinoid was delayed. Patients unsuccessfully treated for bronchial asthma or chronic obstructive pulmonary disease should undergo bronchoscopic examination

Novel transcribed regions in the human genome

We have used genomic tiling arrays to identify transcribed regions throughout the human genome. Analysis of the mapping results of RNA isolated from five cell/tissue types, NB4 cells, NB4 cells treated with retinoic acid (RA), NB4 cells treated with 12-O-tetradecanoylphorbol-13 acetate (TPA), neutrophils, and placenta, throughout the ENCODE region reveals a large number of novel transcribed regions. Interestingly, neutrophils exhibit a great deal of novel expression in several intronic regions. Comparison of the hybridization results of NB4 cells treated with different stimuli relative to untreated cells reveals that many new regions are expressed upon cell differentiation. One such region is the Hox locus, which contains a large number of novel regions expressed in a number of cell types. Analysis of the trinucleotide composition of the novel transcribed regions reveals that it is similar to that of known exons. These results suggest that many of the novel transcribed regions may have a functional role. Copyright 2006, Cold Spring Harbor Laboratory Press © 2006 Cold Spring Harbor Laboratory Press

Systematic Inference of Copy-Number Genotypes from Personal Genome Sequencing Data Reveals Extensive Olfactory Receptor Gene Content Diversity

Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95–99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ∼15% and ∼20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high-throughput sequencing

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A Hidden Markov Model for Copy Number Variant prediction from whole genome resequencing data

Motivation: Copy Number Variants (CNVs) are important genetic factors for studying human diseases. While high-throughput whole genome re-sequencing provides multiple lines of evidence for detecting CNVs, computational algorithms need to be tailored for different type or size of CNVs under different experimental designs. Results: To achieve optimal power and resolution of detecting CNVs at low depth of coverage, we implemented a Hidden Markov Model that integrates both depth of coverage and mate-pair relationship. The novelty of our algorithm is that we infer the likelihood of carrying a deletion jointly from multiple mate pairs in a region without the requirement of a single mate pairs being obvious outliers. By integrating all useful information in a comprehensive model, our method is able to detect medium-size deletions (200-2000bp) at low depth (<10× per sample). We applied the method to simulated data and demonstrate the power of detecting medium-size deletions is close to theoretical values. Availability: A program implemented in Java, Zinfandel, is available at http://www.cs.columbia.edu/~itsik/zinfandel