MedWorm: Genetics

Technique Finds Gene Regulatory Sites Without Knowledge Of Regulators

Genetics News From Medical News Today — Sat, 21 Nov 2009 08:00:00 +0100

A new statistical technique developed by researchers at the University of Illinois allows scientists to scan a genome for specific gene-regulatory regions without requiring prior knowledge of the relevant transcription factors. The technique has been experimentally validated in both the mouse genome and the fruit fly genome. (Source: Genetics News From Medical News Today)

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Schizophrenia Gene's Role May Be Broader, More Potent, Than Thought

Genetics News From Medical News Today — Sat, 21 Nov 2009 08:00:00 +0100

UCSF scientists studying nerve cells in fruit flies have uncovered a new function for a gene whose human equivalent may play a critical role in schizophrenia. Scientists have known that the mutated form of the human gene - one of three consistently associated with schizophrenia - mildly disrupts the transmission of chemical signals between nerve cells in the brain. (Source: Genetics News From Medical News Today)

Ancestry Attracts, But Love Is Blind

Genetics News From Medical News Today — Sat, 21 Nov 2009 08:00:00 +0100

People preferentially marry those with similar ancestry, but their decisions are not necessarily based on hair, eye or skin colour. Research, published in BioMed Central's open access journal Genome Biology, shows that Mexicans mate according to proportions of Native American to European ancestry, while Puerto Ricans are more likely to settle down with someone carrying a similar mix of African and European genes. (Source: Genetics News From Medical News Today)

HMGA2 Is Confirmed To Be Associated with Human Adult Height

Annals of Human Genetics — Sat, 21 Nov 2009 00:00:00 +0100

Recent genome-wide association studies have identified a novel polymorphism, rs1042725, in the HMGA2 gene for human adult height, a highly heritable complex trait. Replications in independent populations are needed to evaluate a positive finding and determine its generality. Thus, we performed a replication study to examine the associations between polymorphisms in HMGA2 and adult height in two US Caucasian populations (an unrelated sample of 998 subjects and a family-based sample of 8385 subjects) and a Chinese population (1638 unrelated Han subjects). We confirmed the association between rs1042725 in HMGA2 and adult height both in the unrelated and family-based Caucasian populations (overall P= 4.25 × 10[minus]9). Another two SNPs (rs7968902 and rs7968682), which were in high linkage di...

Guapa, it's your genetic ancestry I love

New Scientist - Genetics — Fri, 20 Nov 2009 16:48:26 +0100

In Latino populations, love unites people with similar mix of ancestries (Source: New Scientist - Genetics)

Study Examines Challenges Of Diagnosing Neurofibromatosis Type 1-like Syndrome

Genetics News From Medical News Today — Fri, 20 Nov 2009 09:00:00 +0100

An analysis of patients with a syndrome similar to the genetic disorder, neurofibromatosis type 1, indicates that diagnosis may be difficult because of shared clinical findings, such as certain pigmentary characteristics, according to a study in the November 18 issue of JAMA. (Source: Genetics News From Medical News Today)

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Novel motifs distinguish multiple homologues of Polycomb in vertebrates: expansion and diversification of the epigenetic toolkit

BMC Genomics - Latest articles — Fri, 20 Nov 2009 00:00:00 +0100

Conclusions: Our analysis shows that PC is an ancient gene dating back to pre bilaterian origin that has not only been conserved but has also expanded during the evolution of complexity. Unique motifs acquired by each homologue have been maintained for more than 500 millions years indicating their functional relevance in boosting the epigenetic 'tool kit'. We report the presence of a DNA interaction motif adjacent to chromodomain in all vertebrate PC homologues and suggest a three-way 'PC-histoneH3-DNA' interaction that can restrict nucleosome dynamics. The signature motifs of PC homologues and insect specific motif identified in this study pave the way to understand the molecular basis of epigenetic mechanisms. (Source: BMC Genomics - Latest articles)

Attributing Hardy-Weinberg Disequilibrium to Population Stratification and Genetic Association in Case-Control Studies

Annals of Human Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Loci exhibiting Hardy-Weinberg disequilibrium (HWD) are often excluded from association studies, because HWD may indicate genotyping error, population stratification or selection bias. For case-control studies, HWD can result from a genetic effect at the locus. We extend the modelling to accommodate both stratification and genetic effects. Theoretical genotype frequencies and HWD coefficients are derived under a general genetic model for a population with two strata. Maximum likelihood is used to estimate model parameters and a test for lack of fit identifies the models most consistent with the data. Simulations were used to assess the method. The technique was applied to a group of ethnically and clinically heterogeneous kidney stone formers and controls, both exhibiting HWD for the R990G...

Fitness Among Individuals with Early Childhood Deafness: Studies in Alumni Families from Gallaudet University

Annals of Human Genetics — Fri, 20 Nov 2009 00:00:00 +0100

The genetic fitness of an individual is influenced by their phenotype, genotype and family and social structure of the population in which they live. It is likely that the fitness of deaf individuals was quite low in the Western European population during the Middle Ages. The establishment of residential schools for deaf individuals nearly 400 years ago resulted in relaxed genetic selection against deaf individuals which contributed to the improved fitness of deaf individuals in recent times. As part of a study of deaf probands from Gallaudet University, we collected pedigree data, including the mating type and the number and hearing status of the children of 686 deaf adults and 602 of their hearing siblings. Most of these individuals had an onset of severe to profound hearing loss by earl...

Maize Centromere Structure and Evolution: Sequence Analysis of Centromeres 2 and 5 Reveals Dynamic Loci Shaped Primarily by Retrotransposons

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary Centromeres tend to be the last regions to be assembled in genome projects, as their mapping is hampered by their characteristically high repeat DNA content and lack of genetic recombination. Using unique markers derived from these repeat-rich regions, we were able to generate and annotate physical maps of two maize centromeres. Functional centromeres are defined not so much by their primary DNA sequence as by the presence of CENH3, a special histone that replaces canonical histone H3 in centromeric nucleosomes. Little is known about how deposition of CENH3 is regulated, or about the interplay between centromeric repeats and CENH3. By graphing the density of CENH3 nucleosomes onto the physical map, we delineated the functional centromeres in today's maize genome. We then us...

Sequencing, Mapping, and Analysis of 27,455 Maize Full-Length cDNAs

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary To complement the completion of sequencing the maize B73 genome, we sequenced 27,455 full-length cDNAs (FLcDNA) from two maize B73 libraries representing the gene transcripts from most tissues and common abiotic stress conditions. The FLcDNAs are beneficial in determining the exon/intron structure of genes by aligning them to the sequenced genome; 94% of our FLcDNAs aligned to the maize genome. The 27,455 FLcDNAs were compared to gene sequences for rice, sorghum, Arabidopsis, and poplar; 22,874 were found in all four sets, and 1,737 were unique to maize. Two-thirds of the maize genome is composed of a type of repetitive sequence called “transposable elements”; only 5.6% of the FLcDNA sequence contained any segment homologous to these repeats. In addition to our set, the...

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Loss of RNA–Dependent RNA Polymerase 2 (RDR2) Function Causes Widespread and Unexpected Changes in the Expression of Transposons, Genes, and 24-nt Small RNAs

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

In this study, we have shown that a maize mutation of RDR2 causes significant changes in SAM morphology. In combination, these observations indicate the complexity of transcriptome regulation and the crucial roles of RDR2 on transcriptome regulation, chromatin modification, and SAM development. (Source: PLoS Genetics)

RNA-Silencing Enzymes Pol IV and Pol V in Maize: More than one Flavor?

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

(Source: PLoS Genetics)

Caenorhabditis elegans HIM-18/SLX-4 Interacts with SLX-1 and XPF-1 and Maintains Genomic Integrity in the Germline by Processing Recombination Intermediates

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary Homologous recombination (HR) is a process that provides for the accurate and efficient repair of DNA double-strand breaks (DSBs) incurred by cells, thereby maintaining genomic integrity. Proper processing of HR intermediates is critical for biological processes ranging from replication fork restart to the accurate partitioning of chromosomes during meiotic cell divisions. This is further emphasized by the fact that impaired processing of HR intermediates in both mitotic and meiotic cells can result in tumorigenesis and congenital defects. Therefore, the identification of components involved in HR is essential to understand the molecular mechanism of HR. Here, we identify HIM-18/SLX-4 in C. elegans, a protein conserved from yeast to humans that interacts with the nucleases ...

Maize Inbreds Exhibit High Levels of Copy Number Variation (CNV) and Presence/Absence Variation (PAV) in Genome Content

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary There is a growing appreciation for the role of genome structural variation in creating phenotypic variation within a species. Comparative genomic hybridization was used to compare the genome structures of two maize inbred lines, B73 and Mo17. The data reinforce the view that maize is a highly polymorphic species, but also show that there are often large genomic regions that have little or no variation. We identify several hundred sequences that, while present in both B73 and Mo17, have copy number differences in the two genomes. In addition, there are several thousand sequences, including at least 180 sequences annotated as single-copy genes, that are present in one genome but entirely missing in the other genome. This genome content variation leads to differences in trans...

Mu Transposon Insertion Sites and Meiotic Recombination Events Co-Localize with Epigenetic Marks for Open Chromatin across the Maize Genome

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary Genomic insertion sites of Mu transposons were amplified and sequenced via next generation technology, revealing more than 40,000 non-redundant Mu insertion sites that are non-uniformly distributed across the maize genome and within genes. Along chromosomes, frequencies of Mu transposon insertions are strongly correlated with recombination rates. Although both Mu and recombination occur preferentially in genes, gene density does not fully explain these patterns. Instead, the finding that Mu insertions and meiotic recombination sites both concentrate in genomic regions marked with epigenetic marks of open chromatin provides support for the hypothesis that open chromatin enhances rates of both Mu insertion and meiotic recombination. (Source: PLoS Genetics)

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Exceptional Diversity, Non-Random Distribution, and Rapid Evolution of Retroelements in the B73 Maize Genome

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary Although TEs are a major component of all studied plant genomes, and are the most significant contributors to genome structure and evolution in almost all eukaryotes that have been investigated, their properties and reasons for existence are not well understood in any eukaryotic genome. In order to begin a comprehensive study of TE contributions to the structure, function, and evolution of both genes and genomes, we first identified all of the TEs in maize and then investigated whether there were non-random patterns in their dispersal. We used homology and TE structure criteria in an effort to discover all of the retroelements in the recently sequenced genome from maize inbred B73. We found that the retroelements are incredibly diverse in maize, with many hundreds of famili...

Stage-Specific Expression Profiling of Drosophila Spermatogenesis Suggests that Meiotic Sex Chromosome Inactivation Drives Genomic Relocation of Testis-Expressed Genes

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

In this study, we observed meiotic expression reduction for X-linked genes in D. melanogaster through a global gene expression analysis in different phases of spermatogenesis, in agreement with MSCI. In order to test the effects of MSCI on the chromosomal distribution of testis-expressed genes, we analyzed their expression pattern throughout spermatogenesis. First, X chromosome underrepresentation was restricted to testis-biased genes over-expressed in meiosis. Second, we observed that the autosomal genes retroposed from the X chromosome more often showed complementary expression in meiosis to their X-linked parents. These results support MSCI in Drosophila, suggesting its mechanistic role in the evolution of testis-expressed genes. (Source: PLoS Genetics)

Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary Genome-wide association studies (GWAS) of plasma lipoprotein fractions hold great promise for understanding lipid metabolism and its central role in cardiovascular disease and related disorders. Conventional assays for lipoprotein status determine total cholesterol content of low- or high-density lipoprotein particles (LDL-C or HDL-C, respectively) or total plasma triglyceride content (as an estimate of very-low density lipoprotein particle concentration [VLDL]). All three measures have been targets for recent GWAS. However, a more precise target for GWAS of lipoprotein metabolism would be the concentration of the individual lipoprotein particles according to class (LDL, HDL, VLDL) and size (small, medium, and large), all of which can be measured by NMR-based methods. In a ...

Fine-Scale Phylogenetic Discordance across the House Mouse Genome

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary The phylogenetic history of individual genes can differ strongly from the species history if taxa are recently derived, making inferences of a species history from only a handful of genes especially difficult in these cases. Genome-scale data sets now allow phylogenetic histories to be reconstructed from a large number of genes. Although data sets of this size are becoming more common, few studies have characterized variation in phylogenetic history across whole genomes. We summarize fine scale variation in phylogenetic history across the genome of house mice, a recently derived group of subspecies, using a method that combines phylogenetic uncertainty among gene trees. We document substantial variation in phylogenetic history among 14,081 loci and describe a primary histor...

Detailed Analysis of a Contiguous 22-Mb Region of the Maize Genome

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary Maize is a major cereal crop and key experimental system for eukaryotic biology. Previous investigations of the maize genome at the sequence level have primarily focused on analyses of genome survey sequences and BAC contigs. Here we used a comprehensive set of resources to construct an ordered and oriented 22-Mb sequence from chromosome 4 that represents 1% of the maize genome. Genome annotation revealed the presence of 544 genes that are interspersed with transposable elements (TEs), which occupy 83.8% of the sequence. Fifty-one genes were involved in 14 tandem gene clusters and most appear to have arisen after lineage divergence. TEs, especially helitrons, were found to contain gene fragments and were widely distributed in gene-rich regions. Large inversions and unequal ...

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A Dominant Mutation in mediator of paramutation2, One of Three Second-Largest Subunits of a Plant-Specific RNA Polymerase, Disrupts Multiple siRNA Silencing Processes

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary How an individual's genes are activated or silenced is an essential question impacting all fields of biology. Usually gene expression patterns, i.e., which genes are on and which are off in different tissues and during development, are highly reproducible; and those patterns are efficiently reset in the next generation of progeny. Paramutation represents an exception to these genetic rules, in that for certain genes the silencing that is established in an individual is efficiently transmitted to their progeny. Importantly, in these subsequent generations, the silenced gene continues to silence active versions of that gene. Prior work has demonstrated that these heritable gene expression changes are not accompanied by changes in DNA sequence: they are epigenetic. Understandi...

X Chromosome: Expression and Escape

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

(Source: PLoS Genetics)

10 Reasons to be Tantalized by the B73 Maize Genome

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

(Source: PLoS Genetics)

A Genome-Wide Characterization of MicroRNA Genes in Maize

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary MicroRNAs are non-coding RNAs that regulate gene expression post-transcriptionally and play roles in diverse pathways including those acting on development and responses to stress. Here, we describe a genome-wide computational prediction of maize miRNA genes and their characterization with respect to expression, putative targets, evolution following whole genome duplication, and allelic diversity. The structures of unprocessed primary miRNA transcripts were determined by 5′ RACE and 3′ RACE. Expression profiles were surveyed in five tissue types by deep-sequencing of small RNA libraries. We predicted miRNA targets computationally based on the most recent maize protein annotations. Analysis of the predicted functions of target genes, on the basis of gene ontology, suppor...

The Physical and Genetic Framework of the Maize B73 Genome

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

In this study, we used a comprehensive physical and genetic framework map to develop a minimum tiling path (MTP) of over 16,000 BAC clones across the genome. The MTP was generated dynamically and integrated numerous data types, such as in-coming genome sequence, over 8,000 sequence-based genetic markers, and the maize optical map. This allowed us to genetically anchor, order, and orient the majority of the maize physical map and genome sequence to the genetic map. Post-genome sequencing, we constructed a golden path (AGP) of sequence-based pseudomolecules representing the ten chromosomes of the maize B73 genome (B73 RefGen_v1). This unprecedented integration of genetic, physical, and genomic sequence into one framework will greatly facilitate all aspects of plant biological research. (Sour...

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A Single Molecule Scaffold for the Maize Genome

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary The maize genome contains abundant repeats interspersed by low-copy, gene-coding sequences that make it a challenge to sequence; consequently, current BAC sequence assemblies average 11 contigs per clone. The iMap deals with such complexity by the judicious integration of IBM genetic and B73 physical maps, but the B73 genome structure could differ from the IBM population because of genetic recombination and subsequent rearrangements. Accordingly, we report a genome-wide, high-resolution optical map of maize B73 genome that was constructed from the direct analysis of genomic DNA molecules without using genetic markers. The integration of optical and iMap resources with comparisons to FPC maps enabled a uniquely comprehensive and scalable assessment of a given BAC's sequence ...

Diversity of Pol IV Function Is Defined by Mutations at the Maize rmr7 Locus

PLoS Genetics — Fri, 20 Nov 2009 00:00:00 +0100

Author Summary Multicellular plants possess a unique set of DNA–dependent RNA polymerase complexes (RNAPs) that prevent certain repetitious regions of the genome from being copied into stable RNAs. Two distinct RNAPs, termed Pol IV and Pol V, are required for this type of genome-silencing behavior in the eudicot Arabidopsis thaliana, but the mechanism by which these RNAPs accomplish this function is still relatively unknown. Using genetic and molecular methodologies, we identified a Pol IV–type subunit protein as being involved in a process of meiotically-heritable gene silencing in the maize plant known as paramutation. Our analyses of the available plant genome sequences indicate that monocots have a greater potential for RNAP diversity due to having duplicate variants of this parti...

Ligand-specific sequential regulation of transcription factors for differentiation of MCF-7 cells

BMC Genomics - Latest articles — Fri, 20 Nov 2009 00:00:00 +0100

Conclusions: Our analysis indicated that a time-dependent transcriptional regulatory network including c-FOS, FRA-1, and FHL2 is vital in controlling the ERK signaling pathway through a negative feedback loop for MCF-7 cell differentiation. (Source: BMC Genomics - Latest articles)

Expression profiling of rainbow trout testis development identifies evolutionary conserved genes involved in spermatogenesis

BMC Genomics - Latest articles — Fri, 20 Nov 2009 00:00:00 +0100

Conclusion: A comprehensive study of gene expression and associated functions during testis maturation and germ cell differentiation in the rainbow trout is presented. The study identifies new pathways involved during spermatogonia self-renewal or rapid proliferation, meiosis and gamete differentiation, in fish and potentially in all vertebrates. It also provides the necessary basis to further investigate the hormonal and molecular networks that trigger puberty and annual testicular recrudescence in seasonally breeding species. (Source: BMC Genomics - Latest articles)

Transcriptional regulation of tumor suppressor p53 by cAMP-responsive element-binding protein/AMP-activated protein kinase complex in response to glucose deprivation

Genes to Cells — Fri, 20 Nov 2009 00:00:00 +0100

In this study, we found that cAMP-responsive element-binding protein (CREB) collaborates with AMP-activated protein kinase [alpha] (AMPK[alpha]) to regulate the transcription of p53. Luciferase reporter assays showed that the genomic fragment spanning from [minus]531 to [minus]239 of human p53 gene is required for the transactivation of p53 in response to glucose deprivation. Within this region, we found out a putative CREB-binding site. siRNA-mediated knockdown of CREB resulted in a significant inhibition of the up-regulation of p53 and apoptosis under glucose deprivation. Consistent with these observations, glucose deprivation induced the transcription of p53 and CREB. Additionally, glucose deprivation led to an efficient recruitment of CREB onto the promoter region of p53 gene carrying ...

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Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction

Genes to Cells — Fri, 20 Nov 2009 00:00:00 +0100

The activation mechanisms of Src family kinases (SFKs) involve the dissociation of the intramolecular interaction between the Src homology (SH) 3 and kinase domain. This process is mediated by the intermolecular attack of outer ligands to the SH3 domain. By using a yeast two-hybrid screen, we isolated a relevant ligand involved in the activation mechanisms of SFKs. This molecule was found to be identical to a recently recognized kinetochore protein [ndash] designated as centromere protein (CENP)-V [ndash] which is required for the progression of mitosis. We show here that human CENP-V plays further roles in cell dynamics; the proline-rich region of human CENP-V associates with the SH3 domains of SFKs and potently activates SFKs, whereas another domain of CENP-V that possesses a highly cons...

TdT interacting factor 1 enhances TdT ubiquitylation through recruitment of BPOZ-2 into nucleus from cytoplasm

Genes to Cells — Fri, 20 Nov 2009 00:00:00 +0100

We isolated human cDNA clone encoding Bood POZ containing gene type 2 (BPOZ-2) as a gene with a product that binds to TdT interacting factor 1 (TdIF1) using a yeast two-hybrid system. BPOZ-2 is an adaptor for E3 ligase CUL3 and participates in developmental processes. The binding between BPOZ-2 and TdIF1 was confirmed by GST pull-down and immunoprecipitation assays using specific antibodies against BPOZ-2 and TdIF1 in vitro and in vivo. Although when BPOZ-2 solely was expressed in COS7 cells, BPOZ-2 was observed mainly within the cytoplasm, co-transfection of pEGFP-BPOZ-2 and pDsRed-TdIF1 into COS7 cells resulted in co-localization of EGFP-BPOZ-2 and DsRed-TdIF1 within the nucleus. TdIF1 may recruit BPOZ-2 into the nucleus from the cytoplasm by directly binding to BPOZ-2. BPOZ-2 enhanced T...

Transcriptional regulation of human G2A in monocytes/ macrophages: involvement of c/EBPs, Runx and Pu.1

Genes to Cells — Fri, 20 Nov 2009 00:00:00 +0100

G2 accumulation (G2A) is a G-protein coupled receptor, activated by several ligands and stimuli, such as lysophosphatidylcholine (LPC), extracellular low pH and oxidized phospholipids including 9- and 13-hydroxyoctadecadienoic acid, and has been implicated in mediating inflammatory process under oxidative conditions. Recently, it was demonstrated that G2A in monocytes/macrophages plays critical roles in atherosclerosis deterioration, and therefore its transcriptional regulation in monocytes/macrophages is of great interest. Here, we first confirmed the expression of human G2A (hG2A) in lymph nodes, spleen and peripheral blood leukocytes, including monocytes. Thereafter, transcription start site (TSS) of hG2A was determined by 5'-rapid amplification of cDNA ends analysis. In the course of t...

Physical Mapping of Immune Genes in the Tammar Wallaby (Macropus eugenii)

Cytogenetic and Genome Research — Thu, 19 Nov 2009 23:00:00 +0100

Cytogenet Genome Res (DOI:10.1159/000260372) (Source: Cytogenetic and Genome Research)

Mapping quantitative trait loci (QTL) in sheep. I. A new male framework linkage map and QTL for growth rate and body weight.

Genet Sel Evol — Thu, 19 Nov 2009 21:44:03 +0100

Authors: Raadsma HW, Thomson PC, Zenger KR, Cavanagh C, Lam MK, Jonas E, Jones M, Attard G, Palmer D, Nicholas FW A male sheep linkage map comprising 191 microsatellites was generated from a single family of 510 Awassi-Merino backcross progeny. Except for ovine chromosomes 1, 2, 10 and 17, all other chromosomes yielded a LOD score difference greater than 3.0 between the best and second-best map order. The map is on average 11% longer than the Sheep Linkage Map v4.7 male-specific map. This map was employed in quantitative trait loci (QTL) analyses on body-weight and growth-rate traits between birth and 98 weeks of age. A custom maximum likelihood program was developed to map QTL in half-sib families for non-inbred strains (QTL-MLE) and is freely available on request. The new analysis pa...

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Synthesis of N-substituted iminosugars from 2'-carbonyl-C-glycofuranosides.

Carbohydrate Research — Thu, 19 Nov 2009 21:34:05 +0100

Authors: Luo H, Zou W, Shao H Under basic conditions 2'-carbonyl 5-N-substituted-C-glycofuranosides undergo a tandem beta-elimination and intramolecular hetero-Michael addition to form N-substituted iminosugar derivatives in good to excellent yields. PMID: 19917320 [PubMed - in process] (Source: Carbohydrate Research)

Multiple Roles for Heterochromatin Protein 1 Genes in Drosophila.

Annual Review of Genetics — Thu, 19 Nov 2009 20:08:05 +0100

Authors: Vermaak D, Malik HS Heterochromatin is the gene-poor, transposon-rich, late-replicating chromatin compartment that was first cytologically defined more than 70 years ago. The identification of heterochromatin protein 1 (HP1) paved the way for a molecular dissection of this important component of complex eukaryotic genomes. Although initial studies revealed HP1's key role in heterochromatin maintenance and function, more recent studies have discovered a role for HP1 in numerous processes including, surprisingly, euchromatic gene expression. Drosophila genomes possess at least five HP1 paralogs that have significantly different roles, ranging from canonical heterochromatic function at pericentric and telomeric regions to exclusive localization and regulation of euchromatic genes...

ProPhylER: A curated online resource for protein function and structure based on evolutionary constraint analyses [RESOURCES]

Genome Research — Thu, 19 Nov 2009 15:57:35 +0100

ProPhylER (Protein Phylogeny and Evolutionary Rates) is a next-generation curated proteome resource that uses comparative sequence analysis to predict constraint and mutation impact for eukaryotic proteins. Its purpose is to inform any research program for which protein function and structure are relevant, by the predictive power of evolutionary constraint analyses. ProPhylER currently has nearly 9000 clusters of related proteins, including more than 200,000 sequences. It serves data via two interfaces. The "ProPhylER Interface" displays predictive analyses in sequence space; the "CrystalPainter" maps evolutionary constraints onto solved protein structures. Here we summarize ProPhylER's data content and analysis pipeline, demonstrate the use of ProPhylER's interfaces, and evaluate ProPhylE...

Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination [LETTERS]

Genome Research — Thu, 19 Nov 2009 15:57:34 +0100

Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experime...

Gene change in cannibals reveals evolution in action

New Scientist - Genetics — Thu, 19 Nov 2009 14:39:42 +0100

Devastating brain disease caused by human cannibalism promoted protective gene mutation to emerge just 200 years ago (Source: New Scientist - Genetics)

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Cognitive Dysfunction Reversed In Mouse Model Of Down's Syndrome

Genetics News From Medical News Today — Thu, 19 Nov 2009 11:00:00 +0100

A study by neuroscientist William C. Mobley, MD, PhD, chair of the Department of Neurosciences at the University of California, San Diego School of Medicine, and colleagues at Stanford University Medical School has demonstrated a possible new approach to slowing the inevitable progression of cognitive decline found in Down's syndrome. (Source: Genetics News From Medical News Today)

An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity [LETTERS]

Genome Research — Thu, 19 Nov 2009 00:32:52 +0100

Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methionine and glutathione biosynthesis, Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer protection against acetaminophen-induced injury in vivo. Since SMM...

A novel study of Copy Number Variations in Hirschsprung disease using the Multiple Ligation-dependent Probe Amplification (MLPA) technique.

BMC Medical Genetics - Latest articles — Thu, 19 Nov 2009 00:00:00 +0100

Conclusions: Our results indicate that CNVs of the gene coding regions analyzed here are not a common molecular cause of Hirschsprung disease. However, further studies are required to determine the presence of CNVs affecting non-coding regulatory regions, as well as other candidate genes. (Source: BMC Medical Genetics - Latest articles)

A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells

BMC Genomics - Latest articles — Thu, 19 Nov 2009 00:00:00 +0100

Conclusions: These results show for the first time that UCB exposure induces ER stress response as major intracellular homeostasis in surviving neuroblastoma cells in vitro. (Source: BMC Genomics - Latest articles)

Differentially expressed genes for aggressive pecking behaviour in laying hens

BMC Genomics - Latest articles — Thu, 19 Nov 2009 00:00:00 +0100

Conclusion: In conclusion, our study provides new insights into which genes are involved in aggressive behaviours in chickens. Pecking and receiving hens exhibited different gene expression profiles in their brains. Following confirmation, the identification of differentially expressed genes may elucidate how the pecking order forms in laying hens at a molecular level. (Source: BMC Genomics - Latest articles)

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Psychiatric syndromes in individuals with chromosome 18 abnormalities

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics — Thu, 19 Nov 2009 00:00:00 +0100

This study focuses on the presentations of psychiatric syndromes as they relate to specific chromosomal abnormalities of chromosome 18. Twenty-five subjects (13 with an 18q deletion, 9 with 18p tetrasomy, and 3 with an 18p deletion), were interviewed by psychiatrists (blind to specific chromosomal abnormality) using the DIGS (subjects 18 and older) or KSADS-PL (subjects under 18). A consensus best estimation diagnostic process was employed to determine psychiatric syndromes. Oligonucleotide Array Comparative Genomic Hybridization (Agilent Technologies) was utilized to define specific regions of chromosome 18 that were deleted or duplicated. These data were further analyzed to determine critical regions of the chromosome as they relate to phenotypic manifestations in these subjects. 58.3% o...

A systematic association mapping on chromosome 6q in bipolar affective disorder - evidence for the melanin-concentrating-hormone-receptor-2 gene as a risk factor for bipolar affective disorder

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics — Thu, 19 Nov 2009 00:00:00 +0100

Strong evidence of linkage between chromosomal region 6q16-q22 and bipolar affective disorder (BPAD) has previously been reported. We conducted a systematic association mapping of the 6q-linkage interval using 617 SNP markers in a BPAD case-control sample of German descent (cases = 330, controls = 325). In this screening step, 46 SNPs showed nominally significant BPAD-association (P-values between 0.0007 and 0.0484). Although none of the 46 SNPs survived correction for multiple testing, they were genotyped in a second and ethnically matched BPAD sample (cases = 328, controls = 397). At the melanin-concentrating-hormone-receptor-2 (MCHR2) gene, we found nominal association in both the initial and second BPAD samples (combined P = 0.008). This finding was followed up by the genotyping of 17 ...

Biology inspires engineering

Genome Biology — Thu, 19 Nov 2009 00:00:00 +0100

A report of the Cold Spring Harbor Laboratory/Wellcome Trust Meeting on Engineering Principles in Biology, Cambridge, UK, 14-16 October 2009. (Source: Genome Biology)

Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPAR-gamma signaling as potential mechanism for the negative relationships between immune response and lipid metabolism

BMC Genomics - Latest articles — Thu, 19 Nov 2009 00:00:00 +0100

Conclusions: Results provided novel information into the early signaling and metabolic pathways in mammary tissue that are associated with the innate immune response to S. uberis infection. Our study indicated that IMI challenge with S. uberis (strain O140J) elicited a strong transcriptomic response, leading to potent activation of pro-inflammatory pathways that were associated with a marked inhibition of lipid synthesis, stress-activated kinase signaling cascades, and PPAR signaling (most likely PPARgamma). This latter effect may provide a mechanistic explanation for the inverse relationship between immune response and milk fat synthesis. (Source: BMC Genomics - Latest articles)

CORRIGENDUM [Corrigendum]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

(Source: Genetics)

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Ectopic Overproduction of a Sporulation-Specific Transcription Factor Induces Assembly of Prespore-Like Membranous Compartments in Vegetative Cells of Fission Yeast [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Mei4 is a key sporulation-specific transcription factor in fission yeast. Ectopic expression of Mei4 in vegetative cells caused formation of nucleated membranous compartments, which shared common features with normal forespore membranes, thereby perturbing nuclear division. These results suggest why expression of development-specific transcription factors must be strictly controlled. (Source: Genetics)

Removal of the Bloom Syndrome DNA Helicase Extends the Utility of Imprecise Transposon Excision for Making Null Mutations in Drosophila [Genome integrity and transmission]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Transposable elements are frequently used in Drosophila melanogaster for imprecise excision screens to delete genes of interest. However, these screens are highly variable in the number and size of deletions that are recovered. Here, we show that conducting excision screens in mus309 mutant flies that lack DmBlm, the Drosophila ortholog of the Bloom syndrome protein, increases the percentage and overall size of flanking deletions recovered after excision of either P or Minos elements. (Source: Genetics)

Evolution of Sex-Dependent Gene Expression in Three Recently Diverged Species of Drosophila [Genome and systems biology]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Sexual dimorphism in morphological, physiological, and behavioral traits is pervasive in animals, as is the observation of strong sexual dimorphism in genomewide patterns of gene expression in the few species where this has been studied. Studies of transcriptome divergence show that most interspecific transcriptional divergence is highly sex dependent, an observation consistent with the action of sex-dependent natural selection during species divergence. However, few transcriptome evolution studies have been conducted between recently diverged species (<1 MY). Here, we present analyses of sex-biased transcriptome divergence in sexually mature adults of three recently diverged species of Drosophila: Drosophila pseudoobscura, D. persimilis, and D. pseudoobscura bogotana. Data were collect...

Cross-Species RNAi Rescue Platform in Drosophila melanogaster [Genome and systems biology]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

RNAi-mediated gene knockdown in Drosophila melanogaster is a powerful method to analyze loss-of-function phenotypes both in cell culture and in vivo. However, it has also become clear that false positives caused by off-target effects are prevalent, requiring careful validation of RNAi-induced phenotypes. The most rigorous proof that an RNAi-induced phenotype is due to loss of its intended target is to rescue the phenotype by a transgene impervious to RNAi. For large-scale validations in the mouse and Caenorhabditis elegans, this has been accomplished by using bacterial artificial chromosomes (BACs) of related species. However, in Drosophila, this approach is not feasible because transformation of large BACs is inefficient. We have therefore developed a general RNAi rescue approach for Dros...

Identification of a Cis-Acting Regulatory Polymorphism in a Eucalypt COBRA-Like Gene Affecting Cellulose Content [Genetics of complex traits]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

This study demonstrates the potential to reveal functional polymorphisms underlying quantitative traits in low LD populations. (Source: Genetics)

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A Combined-Cross Analysis Reveals Genes With Drug-Specific and Background-Dependent Effects on Drug Sensitivity in Saccharomyces cerevisiae [Genetics of complex traits]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Effective pharmacological therapy is often inhibited by variable drug responses and adverse drug reactions. Dissecting the molecular basis of different drug responses is difficult due to complex interactions involving multiple genes, pathways, and cellular processes. We previously found a single nucleotide polymorphism within cystathionine β-synthase (CYS4) that causes multi-drug sensitivity in a vineyard strain of Saccharomyces cerevisiae. However, not all variation was accounted for by CYS4. To identify additional genes influencing drug sensitivity, we used CYS4 as a covariate and conducted both single- and combined-cross linkage mapping. After eliminating numerous false-positive associations, we identified 16 drug-sensitivity loci, only 3 of which had been previously identified. Of...

Quantitative Genetic Bases of Anthocyanin Variation in Grape (Vitis vinifera L. ssp. sativa) Berry: A Quantitative Trait Locus to Quantitative Trait Nucleotide Integrated Study [Genetics of complex traits]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

The combination of QTL mapping studies of synthetic lines and association mapping studies of natural diversity represents an opportunity to throw light on the genetically based variation of quantitative traits. With the positional information provided through quantitative trait locus (QTL) mapping, which often leads to wide intervals encompassing numerous genes, it is now feasible to directly target candidate genes that are likely to be responsible for the observed variation in completely sequenced genomes and to test their effects through association genetics. This approach was performed in grape, a newly sequenced genome, to decipher the genetic architecture of anthocyanin content. Grapes may be either white or colored, ranging from the lightest pink to the darkest purple tones according...

The Accuracy of Genomic Selection in Norwegian Red Cattle Assessed by Cross-Validation [Genetics of complex traits]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Genomic Selection (GS) is a newly developed tool for the estimation of breeding values for quantitative traits through the use of dense markers covering the whole genome. For a successful application of GS, accuracy of the prediction of genomewide breeding value (GW-EBV) is a key issue to consider. Here we investigated the accuracy and possible bias of GW-EBV prediction, using real bovine SNP genotyping (18,991 SNPs) and phenotypic data of 500 Norwegian Red bulls. The study was performed on milk yield, fat yield, protein yield, first lactation mastitis traits, and calving ease. Three methods, best linear unbiased prediction (G-BLUP), Bayesian statistics (BayesB), and a mixture model approach (MIXTURE), were used to estimate marker effects, and their accuracy and bias were estimated by usin...

The Sheltered Genetic Load Linked to the S Locus in Plants: New Insights From Theoretical and Empirical Approaches in Sporophytic Self-Incompatibility [Population and evolutionary genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Inbreeding depression and mating systems evolution are closely linked, because the purging of deleterious mutations and the fitness of individuals may depend on outcrossing vs. selfing rates. Further, the accumulation of deleterious mutations may vary among genomic regions, especially for genes closely linked to loci under balancing selection. Sporophytic self-incompatibility (SSI) is a common genetic mechanism in angiosperm that enables hermaphrodite plants to avoid selfing and promote outcrossing. The SSI phenotype is determined by the S locus and may depend on dominance relationships among alleles. Since most individuals are heterozygous at the S locus and recombination is suppressed in the S-locus region, it has been suggested that deleterious mutations could accumulate at genes linked...

Closed-Form Two-Locus Sampling Distributions: Accuracy and Universality [Population and evolutionary genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Sampling distributions play an important role in population genetics analyses, but closed-form sampling formulas are generally intractable to obtain. In the presence of recombination, there is no known closed-form sampling formula that holds for an arbitrary recombination rate. However, we recently showed that it is possible to obtain useful closed-form sampling formulas when the population-scaled recombination rate is large. Specifically, in the case of the two-locus infinite-alleles model, we considered an asymptotic expansion of the sampling formula in inverse powers of and obtained closed-form expressions for the first few terms in the expansion. In this article, we generalize this result to an arbitrary finite-alleles mutation model and show that, up to the first few terms in the expa...

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The Population Genetics of Adaptation: Multiple Substitutions on a Smooth Fitness Landscape [Population and evolutionary genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Much recent work in the theoretical study of adaptation has focused on the so-called strong selection–weak mutation (SSWM) limit, wherein adaptation is due to new mutations of definite selective advantage. This work, in turn, has focused on the first step (substitution) during adaptive evolution. Here we extend this theory to allow multiple steps during adaptation. We find analytic solutions to the probability that adaptation follows a certain path during evolution as well as the probability that adaptation arrives at a given genotype regardless of the path taken. We also consider the probability of parallel adaptation and the proportion of the total increase in fitness caused by the first substitution. Our key assumption is that there is no epistasis among beneficial mutations. (Sou...

Population Differentiation as an Indicator of Recent Positive Selection in Humans: An Empirical Evaluation [Population and evolutionary genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

We have evaluated the extent to which SNPs identified by genomewide surveys as showing unusually high levels of population differentiation in humans have experienced recent positive selection, starting from a set of 32 nonsynonymous SNPs in 27 genes highlighted by the HapMap1 project. These SNPs were genotyped again in the HapMap samples and in the Human Genome Diversity Project–Centre d'Etude du Polymorphisme Humain (HGDP–CEPH) panel of 52 populations representing worldwide diversity; extended haplotype homozygosity was investigated around all of them, and full resequence data were examined for 9 genes (5 from public sources and 4 from new data sets). For 7 of the genes, genotyping errors were responsible for an artifactual signal of high population differentiation and for 2, ...

Testing for Spatially Divergent Selection: Comparing QST to FST [Population and evolutionary genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

QST is a standardized measure of the genetic differentiation of a quantitative trait among populations. The distribution of QST's for neutral traits can be predicted from the FST for neutral marker loci. To test for the neutral differentiation of a quantitative trait among populations, it is necessary to ask whether the QST of that trait is in the tail of the probability distribution of neutral traits. This neutral distribution can be estimated using the Lewontin–Krakauer distribution and the FST from a relatively small number of marker loci. We develop a simulation method to test whether the QST of a given trait is consistent with the null hypothesis of selective neutrality over space. The method is most powerful with small mean FST, strong selection, and a large number (>10) of ...

Adaptive Divergence in Experimental Populations of Pseudomonas fluorescens. IV. Genetic Constraints Guide Evolutionary Trajectories in a Parallel Adaptive Radiation [Population and evolutionary genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

The capacity for phenotypic evolution is dependent upon complex webs of functional interactions that connect genotype and phenotype. Wrinkly spreader (WS) genotypes arise repeatedly during the course of a model Pseudomonas adaptive radiation. Previous work showed that the evolution of WS variation was explained in part by spontaneous mutations in wspF, a component of the Wsp-signaling module, but also drew attention to the existence of unknown mutational causes. Here, we identify two new mutational pathways (Aws and Mws) that allow realization of the WS phenotype: in common with the Wsp module these pathways contain a di-guanylate cyclase-encoding gene subject to negative regulation. Together, mutations in the Wsp, Aws, and Mws regulatory modules account for the spectrum of WS phenotype-ge...

stall Encodes an ADAMTS Metalloprotease and Interacts Genetically With Delta in Drosophila Ovarian Follicle Formation [Developmental and behavioral genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

Ovarian follicle formation in Drosophila melanogaster requires stall (stl) gene function, both within and outside the ovary, for follicle individualization, stalk cell intercalation, and oocyte localization. We have identified the stl transcript as CG3622 and confirmed the presence of three alternatively spliced isoforms, contrary to current genome annotation. Here we show that the gene is expressed in both ovarian and brain tissues, which is consistent with previous evidence of an ovary nonautonomous function. On the basis of amino acid sequence, stl encodes a metalloprotease similar to the "a disintegrin and metalloprotease with thrombospondin" (ADAMTS) family. Although stl mutant ovaries fail to maintain the branched structure of the fusome and periodically show improperly localized ooc...

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A Gain-of-Function Screen Identifying Genes Required for Growth and Pattern Formation of the Drosophila melanogaster Wing [Developmental and behavioral genetics]

Genetics — Wed, 18 Nov 2009 16:39:31 +0100

The Drosophila melanogaster wing is a model system for analyzing the genetic control of organ size, shape, and pattern formation. The formation of the wing involves a variety of processes, such as cell growth, proliferation, pattern formation, and differentiation. These developmental processes are under genetic control, and many genes participating in specific aspects of wing development have already being characterized. In this work, we aim to identify novel genes regulating wing growth and patterning. To this end, we have carried out a gain-of-function screen generating novel P-UAS (upstream activating sequences) insertions allowing forced gene expression. We produced 3340 novel P-UAS insertions and isolated 300 that cause a variety of wing phenotypes in combination with a Gal4 driver ex...

A Combinatorial Interplay Among the 1-Aminocyclopropane-1-Carboxylate Isoforms Regulates Ethylene Biosynthesis in Arabidopsis thaliana [Developmental and behavioral genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Ethylene (C2H4) is a unique plant-signaling molecule that regulates numerous developmental processes. The key enzyme in the two-step biosynthetic pathway of ethylene is 1-aminocyclopropane-1-carboxylate synthase (ACS), which catalyzes the conversion of S-adenosylmethionine (AdoMet) to ACC, the precursor of ethylene. To understand the function of this important enzyme, we analyzed the entire family of nine ACS isoforms (ACS1, ACS2, ACS4-9, and ACS11) encoded in the Arabidopsis genome. Our analysis reveals that members of this protein family share an essential function, because individual ACS genes are not essential for Arabidopsis viability, whereas elimination of the entire gene family results in embryonic lethality. Phenotypic characterization of single and multiple mutants unmasks unique...

MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo [Developmental and behavioral genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

PAR proteins (partitioning defective) are major regulators of cell polarity and asymmetric cell division. One of the par genes, par-1, encodes a Ser/Thr kinase that is conserved from yeast to mammals. In Caenorhabditis elegans, par-1 governs asymmetric cell division by ensuring the polar distribution of cell fate determinants. However the precise mechanisms by which PAR-1 regulates asymmetric cell division in C. elegans remain to be elucidated. We performed a genomewide RNAi screen and identified six genes that specifically suppress the embryonic lethal phenotype associated with mutations in par-1. One of these suppressors is mpk-1, the C. elegans homolog of the conserved mitogen activated protein (MAP) kinase ERK. Loss of function of mpk-1 restored embryonic viability, asynchronous cell d...

Dissection of Genetic Factors Modulating Fetal Growth in Cattle Indicates a Substantial Role of the Non-SMC Condensin I Complex, Subunit G (NCAPG) Gene [Developmental and behavioral genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

The increasing evidence of fetal developmental effects on postnatal life, the still unknown fetal growth mechanisms impairing offspring generated by somatic nuclear transfer techniques, and the impact on stillbirth and dystocia in conventional reproduction have generated increasing attention toward mammalian fetal growth. We identified a highly significant quantitative trait locus (QTL) affecting fetal growth on bovine chromosome 6 in a specific resource population, which was set up by consistent use of embryo transfer and foster mothers and, thus, enabled dissection of fetal-specific genetic components of fetal growth. Merging our data with results from other cattle populations differing in historical and geographical origin and with comparative data from human whole-genome association ma...

The Roles of Multiple UNC-40 (DCC) Receptor-Mediated Signals in Determining Neuronal Asymmetry Induced by the UNC-6 (Netrin) Ligand [Developmental and behavioral genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

The polarization of post-mitotic neurons is poorly understood. Preexisting spatially asymmetric cues, distributed within the neuron or as extracellular gradients, could be required for neurons to polarize. Alternatively, neurons might have the intrinsic ability to polarize without any preestablished asymmetric cues. In Caenorhabditis elegans, the UNC-40 (DCC) receptor mediates responses to the extracellular UNC-6 (netrin) guidance cue. For the HSN neuron, an UNC-6 ventral-dorsal gradient asymmetrically localizes UNC-40 to the ventral HSN surface. There an axon forms, which is ventrally directed by UNC-6. In the absence of UNC-6, UNC-40 is equally distributed and the HSN axon travels anteriorly in response to other cues. However, we find that a single amino acid change in the UNC-40 ectodom...

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A Promiscuous Prion: Efficient Induction of [URE3] Prion Formation by Heterologous Prion Domains [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

The [URE3] and [PSI+] prions are the infections amyloid forms of the Saccharomyces cerevisiae proteins Ure2p and Sup35p, respectively. Randomizing the order of the amino acids in the Ure2 and Sup35 prion domains while retaining amino acid composition does not block prion formation, indicating that amino acid composition, not primary sequence, is the predominant feature driving [URE3] and [PSI+] formation. Here we show that Ure2p promiscuously interacts with various compositionally similar proteins to influence [URE3] levels. Overexpression of scrambled Ure2p prion domains efficiently increases de novo formation of wild-type [URE3] in vivo. In vitro, amyloid aggregates of the scrambled prion domains efficiently seed wild-type Ure2p amyloid formation, suggesting that the wild-type and scramb...

The Small, Secreted Immunoglobulin Protein ZIG-3 Maintains Axon Position in Caenorhabditis elegans [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Vertebrate and invertebrate genomes contain scores of small secreted or transmembrane proteins with two immunoglobulin (Ig) domains. Many of them are expressed in the nervous system, yet their function is not well understood. We analyze here knockout alleles of all eight members of a family of small secreted or transmembrane Ig domain proteins, encoded by the Caenorhabditis elegans zig ("zwei Ig Domänen") genes. Most of these family members display the unusual feature of being coexpressed in a single neuron, PVT, whose axon is located along the ventral midline of C. elegans. One of these genes, zig-4, has previously been found to be required for maintaining axon position postembryonically in the ventral nerve cord of C. elegans. We show here that loss of zig-3 function results in simi...

Interlock Formation and Coiling of Meiotic Chromosome Axes During Synapsis [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

The meiotic prophase chromosome has a unique architecture. At the onset of leptotene, the replicated sister chromatids are organized along an axial element. During zygotene, as homologous chromosomes pair and synapse, a synaptonemal complex forms via the assembly of a transverse element between the two axial elements. However, due to the limitations of light and electron microscopy, little is known about chromatin organization with respect to the chromosome axes and about the spatial progression of synapsis in three dimensions. Three-dimensional structured illumination microscopy (3D-SIM) is a new method of superresolution optical microscopy that overcomes the 200-nm diffraction limit of conventional light microscopy and reaches a lateral resolution of at least 100 nm. Using 3D-SIM and ant...

Epithelial Polarity: Interactions Between Junctions and Apical-Basal Machinery [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Epithelial polarity is established and maintained by competition between determinants that define the apical and basolateral domains. Cell–cell adhesion complexes, or adherens junctions, form at the interface of these regions. Mutations in adhesion components as well as apical determinants normally lead to an expansion of the basolateral domain. Here we investigate the genetic relationship between the polarity determinants and adhesion and show that the levels of the adhesion protein Armadillo affect competition. We find that in arm mutants, even a modest reduction in the basolateral component lgl leads to a full apical domain expansion or lgl phenotype. By using an allelic series of Armadillo mutations, we show that there is a threshold at which basolateral expansion can be reversed...

Retrograde Intraflagellar Transport Mutants Identify Complex A Proteins With Multiple Genetic Interactions in Chlamydomonas reinhardtii [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

The intraflagellar transport machinery is required for the assembly of cilia. It has been investigated by biochemical, genetic, and computational methods that have identified at least 21 proteins that assemble into two subcomplexes. It has been hypothesized that complex A is required for retrograde transport. Temperature-sensitive mutations in FLA15 and FLA17 show defects in retrograde intraflagellar transport (IFT) in Chlamydomonas. We show that IFT144 and IFT139, two complex A proteins, are encoded by FLA15 and FLA17, respectively. The fla15 allele is a missense mutation in a conserved cysteine and the fla17 allele is an in-frame deletion of three exons. The flagellar assembly defect of each mutant is rescued by the respective transgenes. In fla15 and fla17 mutants, bulges form in the di...

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MNR2 Regulates Intracellular Magnesium Storage in Saccharomyces cerevisiae [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

We describe a fifth yeast CorA homolog (Mnr2) required for Mg homeostasis. MNR2 gene inactivation was associated with an increase in both the Mg requirement and the Mg content of yeast cells. In Mg-replete conditions, wild-type cells accumulated an intracellular store of Mg that supported growth under deficient conditions. An mnr2 mutant was unable to access this store, suggesting that Mg was trapped in an intracellular compartment. Mnr2 was localized to the vacuole membrane, implicating this organelle in Mg storage. The mnr2 mutant growth and Mg-content phenotypes were dependent on vacuolar proton-ATPase activity, but were unaffected by the loss of mitochondrial Mg uptake, indicating a specific dependence on vacuole function. Overexpression of Mnr2 suppressed the growth defect of an alr1 ...

Suppression of Mitochondrial DNA Instability of Autosomal Dominant Forms of Progressive External Ophthalmoplegia-Associated ANT1 Mutations in Podospora anserina [Cellular genetics]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Maintenance and expression of mitochondrial DNA (mtDNA) are essential for the cell and the organism. In humans, several mutations in the adenine nucleotide translocase gene ANT1 are associated with multiple mtDNA deletions and autosomal dominant forms of progressive external ophthalmoplegia (adPEO). The mechanisms underlying the mtDNA instability are still obscure. A current hypothesis proposes that these pathogenic mutations primarily uncouple the mitochondrial inner membrane, which secondarily causes mtDNA instability. Here we show that the three adPEO-associated mutations equivalent to A114P, L98P, and V289M introduced into the Podospora anserina ANT1 ortholog dominantly cause severe growth defects, decreased reactive oxygen species production (ROS), decreased mitochondrial inner membra...

In Planta Mutagenesis Determines the Functional Regions of the Wheat Puroindoline Proteins [Gene expression]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

This study demonstrates the feasibility of in planta functional analysis of wheat proteins and that the Tryptophan-rich region is the most important region of both PINA and PINB. (Source: Genetics)

The Developmentally Active and Stress-Inducible Noncoding hsr{omega} Gene Is a Novel Regulator of Apoptosis in Drosophila [Gene expression]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

The large nucleus limited noncoding hsr-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsr transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsr transcripts suppressed JNK activation. In a...

Two Distinct Roles for EGL-9 in the Regulation of HIF-1-Mediated Gene Expression in Caenorhabditis elegans [Gene expression]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Oxygen is critically important to metazoan life, and the EGL-9/PHD enzymes are key regulators of hypoxia (low oxygen) response. When oxygen levels are high, the EGL-9/PHD proteins hydroxylate hypoxia-inducible factor (HIF) transcription factors. Once hydroxylated, HIF subunits bind to von Hippel-Lindau (VHL) E3 ligases and are degraded. Prior genetic analyses in Caenorhabditis elegans had shown that EGL-9 also acted through a vhl-1-independent pathway to inhibit HIF-1 transcriptional activity. Here, we characterize this novel EGL-9 function. We employ an array of complementary methods to inhibit EGL-9 hydroxylase activity in vivo. These include hypoxia, hydroxylase inhibitors, mutation of the proline in HIF-1 that is normally modified by EGL-9, and mutation of the EGL-9 catalytic core. Rem...

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Imprinting of the Y Chromosome Influences Dosage Compensation in roX1 roX2 Drosophila melanogaster [Gene expression]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Drosophila melanogaster males have a well-characterized regulatory system that increases X-linked gene expression. This essential process restores the balance between X-linked and autosomal gene products in males. A complex composed of the male-specific lethal (MSL) proteins and RNA is recruited to the body of transcribed X-linked genes where it modifies chromatin to increase expression. The RNA components of this complex, roX1 and roX2 (RNA on the X1, RNA on the X2), are functionally redundant. Males mutated for both roX genes have dramatically reduced survival. We show that reversal of sex chromosome inheritance suppresses lethality in roX1 roX2 males. Genetic tests indicate that the effect on male survival depends upon the presence and source of the Y chromosome, revealing a germ line i...

TEN1 Is Essential for CDC13-Mediated Telomere Capping [Genome integrity and transmission]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Telomere binding proteins protect chromosome ends from degradation and mask chromosome termini from checkpoint surveillance. In Saccharomyces cerevisiae, Cdc13 binds single-stranded G-rich telomere repeats, maintaining telomere integrity and length. Two additional proteins, Ten1 and Stn1, interact with Cdc13 but their contributions to telomere integrity are not well defined. Ten1 is known to prevent accumulation of aberrant single-stranded telomere DNA; whether this results from defective end protection or defective telomere replication is unclear. Here we report our analysis of a new group of ten1 temperature-sensitive (ts) mutants. At permissive temperatures, ten1-ts strains display greatly elongated telomeres. After shift to nonpermissive conditions, however, ten1-ts mutants accumulate ...

Telomerase Is Essential to Alleviate Pif1-Induced Replication Stress at Telomeres [Genome integrity and transmission]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Pif1, an evolutionarily conserved helicase, negatively regulates telomere length by removing telomerase from chromosome ends. Pif1 has also been implicated in DNA replication processes such as Okazaki fragment maturation and replication fork pausing. We find that overexpression of Saccharomyces cervisiae PIF1 results in dose-dependent growth inhibition. Strong overexpression causes relocalization of the DNA damage response factors Rfa1 and Mre11 into nuclear foci and activation of the Rad53 DNA damage checkpoint kinase, indicating that the toxicity is caused by accumulation of DNA damage. We screened the complete set of ~4800 haploid gene deletion mutants and found that moderate overexpression of PIF1, which is only mildly toxic on its own, causes growth defects in strains with mutations i...

Charles Darwin: Genius or Plodder? [Perspectives]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

There is no doubt about the magnitude of Charles Darwin's contributions to science. There has, however, been a long-running debate about how brilliant he was. His kind of intelligence was clearly different from that of the great physicists who are deemed geniuses. Here, the nature of Darwin's intelligence is examined in the light of Darwin's actual style of working. Surprisingly, the world of literature and the field of neurobiology might supply more clues to resolving the puzzle than conventional scientific history. Those clues suggest that the apparent discrepancy between Darwin's achievements and his seemingly pedestrian way of thinking reveals nothing to Darwin's discredit but rather a too narrow and inappropriate set of criteria for "genius." The implications of Darwin's particular cr...

Darwin and Darwinism: The (Alleged) Social Implications of The Origin of Species [Perspectives]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Most scientific theories, even revolutionary ones, change the practice of a particular science but have few consequences for culture or society at large. But Darwinism, it has often been said, is different in this respect. Since the publication of The Origin of Species, many have claimed that Darwinism has a number of profound social implications. Here, I briefly consider three of these: the economic, the political, and the religious. I suggest that, for the most part, these supposed implications have been misconstrued or exaggerated. Indeed, it is reasonably clear that the chain of implication sometimes primarily ran in the opposite direction—from, for instance, economics and political theory to Darwinism. (Source: Genetics)

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Darwin and Genetics [Perspectives]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

Darwin's theory of natural selection lacked an adequate account of inheritance, making it logically incomplete. We review the interaction between evolution and genetics, showing how, unlike Mendel, Darwin's lack of a model of the mechanism of inheritance left him unable to interpret his own data that showed Mendelian ratios, even though he shared with Mendel a more mathematical and probabilistic outlook than most biologists of his time. Darwin's own "pangenesis" model provided a mechanism for generating ample variability on which selection could act. It involved, however, the inheritance of characters acquired during an organism's life, which Darwin himself knew could not explain some evolutionary situations. Once the particulate basis of genetics was understood, it was seen to allow varia...

Celebrating The Origin of Species [Introduction]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

(Source: Genetics)

ISSUE HIGHLIGHTS [Issue Highlights]

Genetics — Wed, 18 Nov 2009 16:39:30 +0100

(Source: Genetics)

Genome-wide mapping of alternative splicing in Arabidopsis thaliana [LETTERS]

Genome Research — Wed, 18 Nov 2009 16:15:52 +0100

Alternative splicing can enhance transcriptome plasticity and proteome diversity. In plants, alternative splicing can be manifested at different developmental stages, and is frequently associated with specific tissue types or environmental conditions such as abiotic stress. We mapped the Arabidopsis transcriptome at single-base resolution using the Illumina platform for ultrahigh-throughput RNA sequencing (RNA-seq). Deep transcriptome sequencing confirmed a majority of annotated introns and identified thousands of novel alternatively spliced mRNA isoforms. Our analysis suggests that at least ~42% of intron-containing genes in Arabidopsis are alternatively spliced; this is significantly higher than previous estimates based on cDNA/expressed sequence tag sequencing. Random validation confirm...

From the editors

Nature Reviews Genetics — Wed, 18 Nov 2009 15:54:22 +0100

Nature Reviews Genetics 10, 813 (2009). doi:10.1038/nrg2716 Certain technologies have changed the face of genetic research — notable examples being DNA cloning, Sanger sequencing and PCR. Now, next-generation sequencing is making waves that are being felt across genetics and genomics.As sequencing costs continue to fall, we will see a rapid increase (Source: Nature Reviews Genetics)

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In Brief

Nature Reviews Genetics — Wed, 18 Nov 2009 15:54:22 +0100

Nature Reviews Genetics 10, 819 (2009). doi:10.1038/nrg2714 Human disease (Source: Nature Reviews Genetics)

In Brief

Nature Reviews Genetics — Wed, 18 Nov 2009 15:54:22 +0100

Nature Reviews Genetics 10, 817 (2009). doi:10.1038/nrg2713 Sequencing technologies (Source: Nature Reviews Genetics)

Ageing: The impact of shrinking telomeres

Nature Reviews Genetics — Wed, 18 Nov 2009 15:54:22 +0100

Nature Reviews Genetics 10, 816 (2009). doi:10.1038/nrg2711 Author: Louisa Flintoft Shortening of telomeres to a critical length triggers a DNA-damage response that contributes to ageing. A new study using a mouse model of accelerated telomere shortening reveals specific transcriptomic and epigenetic changes that provide clues to how telomere shortening is linked to ageing.The Terc (Source: Nature Reviews Genetics)

Genetic and molecular insights into the development and evolution of sexual dimorphism

Nature Reviews Genetics — Wed, 18 Nov 2009 15:54:22 +0100

Nature Reviews Genetics 10, 883 (2009). doi:10.1038/nrg2710 Author: Thomas M. Williams & Sean B. Carroll Nature Reviews Genetics10, 797–804 (2009)The image in Figure 1d of this article was incorrectly attributed to C. Lambert, whereas the source of the figure is actually unknown. The authors apologize for the error. (Source: Nature Reviews Genetics)

The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs

Nature Reviews Genetics — Wed, 18 Nov 2009 15:54:22 +0100

Nature Reviews Genetics 10, 833 (2009). doi:10.1038/nrg2683 Author: Alain Jacquier Over the past few years, techniques have been developed that have allowed the study of transcriptomes without bias from previous genome annotations, which has led to the discovery of a plethora of unexpected RNAs that have no obvious coding capacities. There are many different kinds (Source: Nature Reviews Genetics)

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Vertebrate limb bud development: moving towards integrative analysis of organogenesis

Nature Reviews Genetics — Wed, 18 Nov 2009 15:54:22 +0100

Authors: Rolf Zeller, Javier López-Ríos & Aimée Zuniga The limb bud is of paradigmatic value to understanding vertebrate organogenesis. Recent genetic analysis in mice has revealed the existence of a largely self-regulatory limb bud signalling system that involves many of the pathways that are known to regulate morphogenesis. These findings contrast with the (Source: Nature Reviews Genetics)

Moving Gene Therapy Forward with Mobile DNA

Human Gene Therapy — Wed, 18 Nov 2009 12:05:22 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

Acetaminophen-Related Liver Damage May Be Prevented By Common Herbal Medicine

Genetics News From Medical News Today — Wed, 18 Nov 2009 12:00:00 +0100

A well-known Eastern medicine supplement may help avoid the most common cause of liver transplantation, according to a study by researchers at the Stanford University School of Medicine. The finding came as a surprise to the scientists, who used a number of advanced genetic and genomic techniques in mice to identify a molecular pathway that counters acetaminophen toxicity, which leads to liver failure. (Source: Genetics News From Medical News Today)

TGen Drug Development (TD2) establishes European footprint

TGen News — Wed, 18 Nov 2009 08:00:00 +0100

TD2 and the Institut Paoli-Calmettes (IPC) have forged a strategic alliance that will enable both to maximize their worldwide contributions in the treatment of cancer patients... (Source: TGen News)

Inhibition of vascular endothelial growth factor receptor signaling in angiogenic tumor vasculature.

Advances in Genetics — Wed, 18 Nov 2009 01:08:03 +0100

We describe here one such molecule, SLT-VEGF, a fusion protein containing VEGF121 and the highly cytotoxic catalytic subunit of Shiga-like toxin. PMID: 19914448 [PubMed - in process] (Source: Advances in Genetics)

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Adeno-associated viral vectors and their redirection to cell-type specific receptors.

Advances in Genetics — Wed, 18 Nov 2009 01:08:03 +0100

Authors: Michelfelder S, Trepel M Efficient and specific delivery of genes to the cell type of interest is a crucial issue in gene therapy. Adeno-associated virus (AAV) has gained particular interest as gene vector recently and is therefore the focus of this chapter. Its low frequency of random integration into the genome and the moderate immune response make AAV an attractive platform for vector design. Like in most other vector systems, the tropism of AAV vectors limits their utility for certain tissues especially upon systemic application. This may in part be circumvented by using AAV serotypes with an in vivo gene transduction pattern most closely fitting the needs of the application. Also, the tropism of AAV capsids may be changed by combining parts of the natural serotype diversi...

Tissue-specific targeting based on markers expressed outside endothelial cells.

Advances in Genetics — Wed, 18 Nov 2009 01:08:03 +0100

Authors: Kolonin MG Effective management of various diseases could greatly benefit from improved approaches to selective delivery of imaging agents and drugs to the pathological site while sparing other organs. Vascular targeting based on markers expressed on endothelial cells is the basis for the success of a number of clinical applications. However, targeted treatment of endothelial cells has turned out to often be insufficient for sustained beneficial effects, and the ability to direct therapy to other cells in the organ/tissue may often be essential for long-term efficacy. Therefore, molecular markers associated with the tissue compartments other than the endothelium may represent viable targets for therapeutic, as well as diagnostic, agents. Accumulating evidence indicates that, i...

Ligand-directed cancer gene therapy to angiogenic vasculature.

Advances in Genetics — Wed, 18 Nov 2009 01:08:03 +0100

Authors: Driessen WH, Ozawa MG, Arap W, Pasqualini R Gene therapy strategies in cancer have remained an active area of preclinical and clinical research. One of the current limitations to successful trials is the relative transduction efficiency to produce a therapeutic effect. While intratumoral injections are the mainstay of many treatment regimens to date, this approach is hindered by hydrostatic pressures within the tumor and is not always applicable to all tumor subtypes. Vascular-targeting strategies introduce an alternative method to deliver vectors with higher local concentrations and minimization of systemic toxicity. Moreover, therapeutic targeting of angiogenic vasculature often leads to enhanced bystander effects, improving efficacy. While identification of functional and s...

High-resolution mapping of the Brassica napus Rfp restorer locus using Arabidopsis-derived molecular markers.

TAG. Theoretical and Applied Genetics — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Formanová N, Stollar R, Geddy R, Mahé L, Laforest M, Landry BS, Brown GG The two forms of cytoplasmic male sterility (CMS) native to the oilseed rape or canola species Brassica napus, nap and pol, have novel features that may provide insight into the molecular mechanisms through which CMS/nuclear restorer systems evolve. One such feature is the finding that the distinct nuclear restorer genes for the two systems represent different alleles or haplotypes of the same nuclear locus. Improved understanding of how these systems have evolved will require molecular cloning and characterization of this novel locus. We have employed an approach that exploits the regional co-linearity between the Arabidopsis and Brassica genomes to construct a high-resolution genetic map of th...

Pleiotropy of the branching locus (B) masks linked and unlinked quantitative trait loci affecting seed traits in sunflower.

TAG. Theoretical and Applied Genetics — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Bachlava E, Tang S, Pizarro G, Schuppert GF, Brunick RK, Draeger D, Leon A, Hahn V, Knapp SJ The discovery of unbranched, monocephalic natural variants was pivotal for the domestication of sunflower (Helianthus annuus L.). The branching locus (B), one of several loci apparently targeted by aboriginal selection for monocephaly, pleiotropically affects plant, seed and capitula morphology and, when segregating, confounds the discovery of favorable alleles for seed yield and other traits. The present study was undertaken to gain deeper insights into the genetics of branching and seed traits affected by branching. We produced an unbranched hybrid testcross recombinant inbred line (TC-RIL) population by crossing branched (bb) and unbranched (BB) RILs to an unbranched (BB) tester. Th...

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Complex genomic organization of Indian muntjac centromeric DNA.

Chromosome Research — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Cheng YM, Li TS, Hsieh LJ, Hsu PC, Li YC, Lin CC A 69-kb Indian muntjac bacterial artificial chromosome (BAC) clone that screened positive for Cervid satellites I and IV was selected for complete sequence analysis and further characterization. The sequences of this BAC clone were found in the centromeres and in some interstitial sites of Indian muntjac chromosomes. Sequence analyses showed that the BAC clone contained a 14.5 kb Cervid satellite I-like DNA element and a 9 kb Cervid satellite IV-like DNA element. In addition, it contained 51 regions each organized in a complex fashion, with sequences homology to intersperse repetitive sequences such as LINEs, SINEs, LTRs, other published DNA elements, and unassigned sequences. The FISH patterns of seven non-satellite sequence el...

Genome-wide approaches to determining origin distribution.

Chromosome Research — Wed, 18 Nov 2009 00:00:00 +0100

Authors: Cadoret JC, Prioleau MN Genome integrity depends upon a highly co-ordinated process that ensures the exact duplication of the genome at each cell cycle. Genomic mapping of DNA replication starting points in mammals, known as origins of replication, is an important step towards our understanding of how this essential mechanism is regulated throughout complex genomes. Two recent studies carried out in both human and mouse cells have revealed a strong association between replication origins and transcriptional regulatory elements. This strong overlap raises the question of how gene deserts, also lacking replication origins, are properly replicated in conditions where replication is disrupted. It also provides valuable information forward the identification of key regulatory facto...

CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features

Genome Biology — Wed, 18 Nov 2009 00:00:00 +0100

Conclusion: Our work reveals several key differences among CTCF occupancy-based classes and suggests a critical, yet distinct functional role played by low-occupancy sites. (Source: Genome Biology)

Complexity of genome evolution by segmental rearrangement in Brassica rapa revealed by sequence-level analysis

BMC Genomics - Latest articles — Wed, 18 Nov 2009 00:00:00 +0100

Conclusions: Our results show that previous studies of segmental collinearity between the A. thaliana, Brassica and ancestral karyotype genomes, although very useful, represent over-simplifications of their true relationships. The presence of numerous cryptic collinear genome segments and the frequent occurrence of segmental inversions mean that inference of the positions of genes in B. rapa based on the locations of orthologues in A. thaliana can be misleading. Our results will be of relevance to a wide range of plants that have polyploid genomes, many of which are being considered according to a paradigm of comprising conserved synteny blocks with respect to sequenced, related genomes. (Source: BMC Genomics - Latest articles)

Comparative transcripts profiling reveals new insight into molecular processes regulating lycopene accumulation in a sweet orange (Citrus sinensis) red-flesh mutant

BMC Genomics - Latest articles — Wed, 18 Nov 2009 00:00:00 +0100

Conclusion: This study provided a global picture of the gene expression changes in a sweet orange red-flesh mutant as compared to the wild type. Interpretation of the differentially expressed genes revealed new insight into the molecular processes regulating lycopene accumulation in the sweet orange red-flesh mutant. (Source: BMC Genomics - Latest articles)

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Gametic gene flow method accounts for genomic imprinting

Journal of Animal Breeding and Genetics — Wed, 18 Nov 2009 00:00:00 +0100

Findings within the last 15 years emphasize the possible role of genomic imprinting for trait expression in livestock species. In genetic evaluation, genomically imprinted traits can be treated by models with two different breeding values per animal; one accounts for the paternal and the other for the maternal expression pattern. Relative weighting factors for these breeding values were derived by a generalized version of the discounted gene flow method, which was extended to a gametic level to account for parent-of-origin effects. The gametic approach proved also useful for calculating the expected increase in inbreeding induced by one round of selection and its dynamics over time. The gametic gene flow method was applied to a hypothetical pig breeding programme. Relative weighting factor...

Computing options for multiple-trait test-day random regression models while accounting for heat tolerance

Journal of Animal Breeding and Genetics — Wed, 18 Nov 2009 00:00:00 +0100

Data included 90 242 799 test day records from first, second and third parities of 5 402 484 Holstein cows and 9 326 754 animals in the pedigree. Additionally, daily temperature humidity indexes (THI) from 202 weather stations were available. The fixed effects included herd test day, age at calving, milking frequency and days in milk classes (DIM). Random effects were additive genetic, permanent environment and herd-year and were fit as random regressions. Covariates included linear splines with four knots at 5, 50, 200 and 305 DIM and a function of THI. Mixed model equations were solved using an iteration on data program with a preconditioned conjugate gradient algorithm. Preconditioners used were diagonal (D), block diagonal due to traits (BT) and block diagonal due to traits and correla...

Horizontal gene transfer and diverse functional constrains within a common replication-partitioning system in Alphaproteobacteria: the repABC operon

BMC Genomics - Latest articles — Wed, 18 Nov 2009 00:00:00 +0100

Conclusions: Horizontal gene transfer with conservation of the repABC operon structure provides a highly dynamic operon in which each member of this operon has its own evolutionary dynamics. In addition, it seems that different incompatibility groups present in the same species have different degrees of adaptation to their host genomes, in proportion to the amount of time the incompatibility group has coexisted with the host genome. (Source: BMC Genomics - Latest articles)

Adaptation of the short intergenic spacers between co-directional genes to the Shine-Dalgarno motif among prokaryote genomes

BMC Genomics - Latest articles — Wed, 18 Nov 2009 00:00:00 +0100

Conclusion: The SD presence makes the intergenic lengths from 5 to 8 bps less frequent and causes an adaptation of the stop codon usage. Our results introduce new elements to the discussion of which factors affect the intergenic lengths, which cannot be totally explained by the pressure to compact the prokaryote genomes. (Source: BMC Genomics - Latest articles)

Novel variants identified in methyl-CpG-binding domain genes in autistic individuals

Neurogenetics — Tue, 17 Nov 2009 23:48:49 +0100

Abstract Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4. A total of 46 alterations were identified in the four genes, including ten missense changes and two deletions that alter coding sequence. Several are either unique to our autistic population or cosegregate with affected individuals within a family, suggesting a possible relation of these varia...

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Genetic analysis of ABCG2 gene C421A polymorphism with gout disease in Chinese Han male population

Human Genetics — Tue, 17 Nov 2009 23:47:37 +0100

Content Type Journal ArticleCategory Short ReportDOI 10.1007/s00439-009-0760-4Authors Binbin Wang, Peking Union Medical College Graduate School Beijing ChinaZhimin Miao, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaShiguo Liu, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaJing Wang, Peking Union Medical College Graduate School Beijing ChinaShiyi Zhou, Peking Union Medical College Graduate School Beijing ChinaLin Han, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaDongmei Meng, Gout laboratory, Medical School Hospital of Qingdao University 16 Jiangsu Road Qingdao 266003 ChinaYunlong Wang, Gout laboratory, Medical School Hospital o...

The association of the MYH9 gene and kidney outcomes in American Indians: the Strong Heart Family Study

Human Genetics — Tue, 17 Nov 2009 23:47:37 +0100

In conclusion, common variants in MYH9 polymorphisms may not confer an increased risk of CKD in American Indian populations. Identification of the actual functional genetic variation responsible for the associations seen in African-Americans will likely help to clarify the lack of replication of this gene in our population of American Indians. Content Type Journal ArticleCategory Original InvestigationDOI 10.1007/s00439-009-0769-8Authors Nora Franceschini, University of North Carolina Department of Epidemiology 137 E. Franklin St., Suite 306 CB#8050 Chapel Hill NC 27514 USAV. Saroja Voruganti, Southwest Foundation for Biomedical Research Department of Genetics San Antonio TX USAKarin Haack, Southwest Foundation for Biomedical Research Department of Genetics San Antonio TX USALaura A...

The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders

Human Genetics — Tue, 17 Nov 2009 23:47:37 +0100

This study examined the association of a promoter polymorphism of the leptin gene (LEP), G-2548A (rs7799039), and two non-synonymous single nucleotide polymorphisms of the leptin receptor gene (LEPR), K109R (rs1137100) and Q223R (rs1137101), with body weight, body mass index (BMI) and obesity (BMI ≥ 30) in Pacific Islanders. A total of 745 Austronesian (AN)-speaking participants were analyzed after adjusting for age, gender, and population differences. The results revealed that carriers of the 223Q alleles of LEPR had significantly higher body weight (P = 0.0009) and BMI (P = 0.0022) than non-carriers (i.e., 223R homozygotes); furthermore, the 223Q carriers also had a significantly higher risk of obesity in comparison to non-carriers (P = 0.022...

CG dinucleotide periodicities recognized by the Dnmt3a–Dnmt3L complex are distinctive at retroelements and imprinted domains

Mammalian Genome — Tue, 17 Nov 2009 23:39:32 +0100

Abstract The Dnmt3a and Dnmt3L genes are critical mediators of cytosine methylation during gametogenesis, with major actions noted at transposable elements and imprinted loci. The Dnmt3a–Dnmt3L complex was recently described to have preferential activity at CG dinucleotides located 8-10 bp apart. Because cytosine methylation is heterogeneously distributed in the genome, we tested whether this relative sequence preference explains the effects of mutation of the Dnmt3a and Dnmt3L genes using bioinformatic analysis. We found that the human and mouse genomes are significantly enriched in a CG dinucleotide periodicity of 2 bp, leading to an increased frequency of CGs spaced 8 bp apart that represent widespread targets for this protein complex. When we broke down...

The Reasons for Nursing Home Entry in an Adult Day Care Population: Caregiver Reports Versus Regression Results

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

This article aims to compare reasons for nursing home entry determined through a regression of baseline predictors to relatives’ perceptions of reasons for entry. Participants included 201 community-residing members of 5 senior day care centers in Maryland. Through a prospective design, statistical predictors using Cox regressions were compared to the relatives’ reports of reasons for nursing home entry. These reports identified the most common reasons for nursing home entry as deterioration of independence and confusion. Behavior problems were also reported for almost half of the participants. In contrast, strong baseline statistical predictors of institutionalization were depressed affect, number of psychiatric diagnoses, a diagnosis of dementia, and age. Because of its stron...

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Functional Consequences of Subcortical White Matter Lesions and MRI-Defined Brain Infarct in an Elderly General Population

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

This study suggests that the single and especially the combined occurrence of common vascular brain lesions are associated with functional impairment. Identifying individuals with severe WML combined with MRI-defined brain infarct can help better understand the development of marked impairments in old age. (Source: Journal of Geriatric Psychiatry and Neurology)

Cognitive Impairment in Older Adults Without Dementia: Clinical and Pathologic Outcomes in a Community-Based Sample

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

This study examines clinical and neuropathologic characteristics of 37 participants in a community-based dementia series who had cognitive complaints at enrollment but did not meet dementia criteria. Participants had neuropsychological testing, were followed until death, and underwent autopsy. Twenty-four participants progressed to dementia, and their baseline characteristics were analyzed. Of the 24, 13 met criteria for neuropathologic Alzheimer disease (AD). The 13 participants who progressed to neuropathologic AD (mean intake age 78.5 ± 7.7, mean enrollment 6.4 ± 2.1 years) performed worse than the 11 who progressed to neuropathologic non-AD dementias (mean intake age 79.0 ± 6.0, mean enrollment 6.0 ± 3.2 years) on baseline Wechsler Memory Scale (WMS) delayed...

Consistency of Clinical Diagnosis of Dementia in NEDICES: A Population-Based Longitudinal Study in Spain

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

Conclusions: The diagnosis of dementia was highly accurate in this population-based, Spanish cohort study, and our prevalence figures agree with other European surveys. Given the high cost and difficulties of population rescreening and its relatively low yield, we conclude that a single 2-phase investigation (screening followed by clinical examination) provides accurate information for most population-based prevalence studies of dementia. (Source: Journal of Geriatric Psychiatry and Neurology)

Clock Test Deficits Are Associated With Semantic Memory Impairment in Alzheimer Disease

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

Based on previous findings, we hypothesized that Clock Test deficits in patients with Alzheimer disease (AD) are associated primarily with the impairment of semantic memory regarding the appearance and functionality of a clock. To scrutinize this hypothesis, we developed a Clock Questionnaire that examined the semantic knowledge of the concept of a ‘‘Clock’’ and correlated scores from the questionnaire with performance in Clock Drawing, Clock Setting, and Clock Reading by healthy control participants and patients with mild cognitive impairment, early AD, and progressed AD. The Rey-Osterrieth-Complex-Figure is known to measure both visuospatial abilities and executive functions, and was chosen as a control variable. We found that deteriorated semantic memory best pre...

Assessing Cognition in Parkinson Disease: Use of the Cognitive Linguistic Quick Test

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

Conclusions: The CLQT is a valuable instrument in assessing cognitive dysfunction in PD. The CLQT is superior to the MMSE as it also provides cognitive domain-specific information. (Source: Journal of Geriatric Psychiatry and Neurology)

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Depressive Symptoms in Parkinson Disease Correlate With Impaired Global and Specific Cognitive Performance

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

Consecutive patients in a Movement Disorders Center with Parkinson disease (PD) were offered to undergo complete neuropsychological testing and to complete the Beck Depression Inventory (BDI), regardless of their cognitive and behavioral status. A total of 82 patients were included in this cross-sectional study and had a mean age of 67.7 years, formal education of 14.8 years, PD duration of 101 months, Unified Parkinson Disease Rating Scale—Motor ‘‘off’’ score of 36.96, Mini-Mental State Examination (MMSE) score of 27.8 (range 19-30), and BDI score of 10.23 (SD 8.65). Beck Depression Inventory scores did not correlate with disease duration or motor scores but inversely correlated with the MMSE scores (r = —0.40; P < .001) and total Dementia Rating Sca...

Depressive Symptoms and Metabolic Syndrome: Selective Association in Older Women

Journal of Geriatric Psychiatry and Neurology — Tue, 17 Nov 2009 23:18:52 +0100

The metabolic syndrome (MetS) is being increasingly found in older populations. Depressive symptoms are prevalent in elderly populations, and they are associated with adverse outcomes, chiefly cardiovascular. The aim of this study was to evaluate the association of the 30-item geriatric depression scale (GDS) score with MetS, as defined according to the National Cholesterol Education Program’s Adult Treatment Panel III (ATP-III) criteria, in all 353 participants aged 75+ years living in Tuscania (Italy). Metabolic syndrome was associated with the GDS score in a multivariable linear regression analysis in women (β s= 2.14, 95% CI = 0.14 to 4.14; P = .036), but not in men (β = —.84, 95% CI = —3.17 to 1.49; P = .476), after adjusting. Analysis of the interaction te...

T Cell Receptor (TCR) Gene Transfer with Lentiviral Vectors Allows Efficient Redirection of Tumor Specificity in Naive and Memory T Cells Without Prior Stimulation of Endogenous TCR

Human Gene Therapy — Tue, 17 Nov 2009 21:39:10 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

NIH Appoints Eric D. Green, M.D., Ph.D. To Be Director Of The National Human Genome Research Institute

NHGRI Press Releases — Tue, 17 Nov 2009 17:00:00 +0100

After an extensive national search, Francis S. Collins, M.D., Ph.D., director of the National Institutes of Health (NIH), announces the appointment of Eric D. Green, M.D., Ph.D., to be director of the National Human Genome Research Institute (NHGRI), one of the 27 institutes and centers that comprise NIH. It is the first time an institute director has risen to lead the entire NIH and subsequently picked his own successor. (Source: NHGRI Press Releases)

Controllable Expansion of Primary Cardiomyocytes by Reversible Immortalization

Human Gene Therapy — Tue, 17 Nov 2009 16:31:56 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

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Therapeutic Vaccination with an Interleukin-2–Interferon-γ-Secreting Allogeneic Tumor Vaccine in Patients with Progressive Castration-Resistant Prostate Cancer: A Phase I/II Trial

Human Gene Therapy — Tue, 17 Nov 2009 16:31:35 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

Scientists Follow Their Noses When Investigating Muscle Repair

Genetics News From Medical News Today — Tue, 17 Nov 2009 12:00:00 +0100

When muscle cells need repair, they use odor-detecting tools found in the nose to start the process, researchers have discovered. The results are published online and scheduled for publication in the November issue of the journal Developmental Cell Found on the surfaces of neurons inside the nose, odorant receptors are molecules that bind and respond to substances wafting through the air. (Source: Genetics News From Medical News Today)

Mutation In A MiroRNA: New Cause Of Osteoporosis

Genetics News From Medical News Today — Tue, 17 Nov 2009 12:00:00 +0100

Many biological processes are controlled by small molecules known as microRNAs, which work by suppressing the expression of specific sets of genes. Xiang-Hang Luo and colleagues, at Second Xiangya Hospital of Central South University, People's Republic of China, have now identified a previously unknown microRNA (miR-2861) as crucial to bone maintenance in mice and humans. (Source: Genetics News From Medical News Today)

Postmortem Genetic Tests After Sudden Death May Provide Less Expensive Way To Identify Risk To Surviving Relatives

Genetics News From Medical News Today — Tue, 17 Nov 2009 11:00:00 +0100

Targeted postmortem testing to identify genetic mutations associated with sudden unexplained death (SUD) is an effective and less expensive way to determine risk to relatives than comprehensive cardiac testing of first degree relatives, according to research presented at the American Heart Association's Scientific Sessions 2009. (Source: Genetics News From Medical News Today)

A fast algorithm for estimating transmission probabilities in QTL detection designs with dense maps.

Genet Sel Evol — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Elsen JM, Filangi O, Gilbert H, Le Roy P, Moreno C ABSTRACT: For an autosomal locus, four transmission events are possible from the parents to a progeny, specified by the grand parental origin of the alleles inherited by this individual. Computing the probabilities of these transmission events is essential to perform QTL detection methods. A fast algorithm for the estimation of these probabilities conditional to parental phases is developed. It is adapted to classical QTL detection designs applied to outbred populations, in particular to designed composed of half and / or full sib families. It assumes the absence of interference. The theory is fully developed and an example given. PMID: 19919698 [PubMed - as supplied by publisher] (Source: Genet Sel Evol)

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Enriched partial correlations in genome-wide gene expression profiles of hybrids (A. thaliana): a systems biological approach towards the molecular basis of heterosis.

TAG. Theoretical and Applied Genetics — Tue, 17 Nov 2009 00:00:00 +0100

Authors: Andorf S, Selbig J, Altmann T, Poos K, Witucka-Wall H, Repsilber D Heterosis is a well-known phenomenon but the underlying molecular mechanisms are not yet established. To contribute to the understanding of heterosis at the molecular level, we analyzed genome-wide gene expression profile data of Arabidopsis thaliana in a systems biological approach. We used partial correlations to estimate the global interaction structure of regulatory networks. Our hypothesis states that heterosis comes with an increased number of partial correlations which we interpret as increased numbers of regulatory interactions leading to enlarged adaptability of the hybrids. This hypothesis is true for mid-parent heterosis for our dataset of gene expression in two homozygous parental lines and their re...

COSII genetic maps of two diploid Nicotiana species provide a detailed picture of synteny with tomato and insights into chromosome evolution in tetraploid N. tabacum.

TAG. Theoretical and Applied Genetics — Tue, 17 Nov 2009 00:00:00 +0100

In conclusion, these COSII and SSR markers link the cultivated tobacco map to those of wild diploid Nicotiana species and tomato, thus providing a platform for cross-reference of genetic and genomic information among them as well as other solanaceous species including potato, eggplant, pepper and the closely allied coffee (Rubiaceae). Therefore they will facilitate genetic research in the genus Nicotiana. PMID: 19921141 [PubMed - as supplied by publisher] (Source: TAG. Theoretical and Applied Genetics)

Mixed model approaches for the identification of QTLs within a maize hybrid breeding program.

TAG. Theoretical and Applied Genetics — Tue, 17 Nov 2009 00:00:00 +0100

Authors: van Eeuwijk FA, Boer M, Totir LR, Bink M, Wright D, Winkler CR, Podlich D, Boldman K, Baumgarten A, Smalley M, Arbelbide M, Ter Braak CJ, Cooper M Two outlines for mixed model based approaches to quantitative trait locus (QTL) mapping in existing maize hybrid selection programs are presented: a restricted maximum likelihood (REML) and a Bayesian Markov Chain Monte Carlo (MCMC) approach. The methods use the in-silico-mapping procedure developed by Parisseaux and Bernardo (2004) as a starting point. The original single-point approach is extended to a multi-point approach that facilitates interval mapping procedures. For computational and conceptual reasons, we partition the full set of relationships from founders to parents of hybrids into two types of relations by defining so-c...

Identification of genes associated with multiple cancers via integrative analysis

BMC Genomics - Latest articles — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: The Mc.TGD can identify a short list of genes associated with one or multiple types of cancers. The identified genes are considerably different from those identified using meta analysis or analysis of marginal effects. (Source: BMC Genomics - Latest articles)

Down syndrome: Comments and reflections on the 50th anniversary of Lejeune's discovery

American Journal of Medical Genetics Part A — Tue, 17 Nov 2009 00:00:00 +0100

Over the past some 160 years, the study of Down syndrome (DS) went from early efforts of differentiating it from cretinism (Séguin) to its establishment as a specific nosologic category of mental deficiency (Down) and subsequent attempts to infer its cause. DS was known to be an overwhelmingly sporadic disorder, concordant in MZ and discordant in DZ twins and associated with increased maternal reproductive age (Penrose). Beginning in the 1920s and based in part on phenotype analysis and early cytogenetic insights in Drosophilia, several clinicians (Halbertsma, Waardenburg, Bleyer, Fanconi) and the geneticist C.B. Davenport postulated that DS might be due to a chromosome abnormality; only Davenport, with T.S. Painter, made an actual attempt to perform a clinical/cytological study (with inc...

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Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq

Genome Biology — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: We find that ChIP-seq can be used not only to create gene regulatory maps but also to predict molecular interactions and to inform on the mechanisms for common quantitative variation. (Source: Genome Biology)

BioGPS: an extensible and customizable portal for organizing and querying gene annotation resources

Genome Biology — Tue, 17 Nov 2009 00:00:00 +0100

Online gene annotation resources are indispensable for analysis of genomics data. However, the landscape of these online resources is highly fragmented, and scientists often visit dozens of these sites for each gene in a candidate gene list. Here, we introduce BioGPS (http://biogps.gnf.org), a centralized gene portal for aggregating distributed gene annotation resources. Moreover, BioGPS embraces the principle of community intelligence, enabling any user to easily and directly contribute to the BioGPS platform. (Source: Genome Biology)

Tunicate mitogenomics and phylogenetics: peculiarities of the Herdmania momus mitochondrial genome and support for the new chordate phylogeny

BMC Genomics - Latest articles — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: This is the first mitogenomic study supporting the new chordate phylogeny revealed by recent phylogenomic analyses. It illustrates the beneficial effects of an increased taxon sampling coupled with the use of more realistic amino acid substitution models for the reconstruction of animal phylogeny. (Source: BMC Genomics - Latest articles)

Nonsyndromic alar clefts: Report of five Brazilian patients

American Journal of Medical Genetics Part A — Tue, 17 Nov 2009 00:00:00 +0100

Nonsyndromic alar clefts are rare and they range from a small notch to variable size of clefts of the nasal ala. Usually they are restricted to the alar region, but other minor anomalies such as midline nasal sinuses and small midline or "northbound" clefts can be present. To date all reported cases of nonsyndromic alar clefts have been sporadic. Here we report on five new cases of isolated and nonsyndromic alar clefts. © 2009 Wiley-Liss, Inc. (Source: American Journal of Medical Genetics Part A)

Functional polymorphism of cytotoxic T-lymphocyte antigen 4 and nasopharyngeal carcinoma susceptibility in a Chinese population

International Journal of Immunogenetics — Tue, 17 Nov 2009 00:00:00 +0100

In this study, we performed a case[ndash]control study in a Chinese population. Our result showed that the CTLA-4 +49 A>G polymorphism is associated with NPC susceptibility. The subjects carrying the CTLA-4 +49 AA genotype have a [sim]1.8-fold increased risk of NPC (adjust OR 1.83; 95% CI, 1.16[ndash]2.93) when compared with the GG genotype. (Source: International Journal of Immunogenetics)

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Roles of mammalian sterile 20-like kinase 2-dependent phosphorylations of Mps one binder 1B in the activation of nuclear Dbf2-related kinases

Genes to Cells — Tue, 17 Nov 2009 00:00:00 +0100

In this study, we quantified the phosphorylation of Thr74 using the phosphorylated Thr74-specific antibody. Thr74 is indeed phosphorylated by MST2, but the efficiency is low, suggesting that MOB1B can activate NDR kinases without the phosphorylation of Thr74. We also showed that the phosphorylated MOB1B activates NDR1 T444D and LATS2 T1041D, in which threonine residues phosphorylated by MST kinases are replaced with phosphorylation-mimicking aspartic acid, more efficiently than the unphosphorylated MOB1B does. This finding supports that the phosphorylation of MOB1B enhances its ability as a direct activator of NDR kinases. (Source: Genes to Cells)

Pharmacological Activation of Guanine Nucleotide Exchange Factors for the Small GTPase Rap1 Recruits High-Affinity β1 Integrins as Coreceptors for Parvovirus B19: Improved Ex Vivo Gene Transfer to Human Erythroid Progenitor Cells

Human Gene Therapy — Mon, 16 Nov 2009 17:32:02 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

Intravitreal Adenoviral 15-Lipoxygenase-1 Gene Transfer Prevents Vascular Endothelial Growth Factor A-Induced Neovascularization in Rabbit Eyes

Human Gene Therapy — Mon, 16 Nov 2009 17:00:58 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)

Ex Vivo Serotype-Specific Transduction of Equine Joint Tissue by Self-Complementary Adeno-Associated Viral Vectors

Human Gene Therapy — Mon, 16 Nov 2009 17:00:42 +0100

Human Gene Therapy , Vol. 0, No. 0. (Source: Human Gene Therapy)