Ancient DNA from Hunter-Gatherer and Farmer Groups from Northern Spain Supports a Random Dispersion Model for the Neolithic Expansion into Europe

10 p.

A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

Accuracy in Copy Number Calling by qPCR and PRT : A Matter of DNA

7 p.

The Foraging Ecology of the Mountain Long-Eared Bat Plecotus macrobullaris Revealed with DNA Mini-Barcodes

10 p.

The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event

6 p.

Association analyses of DNA polymorphisms in bovine SREBP-1, LXRα,FADS1 genes with fatty acid composition in Canadian commercial crossbred beef steers

Two previously reported DNA polymorphisms of sterol regulatory element binding transcription factor 1 (SREBP1) and liver X receptor alpha (LXRα) and two DNA polymorphisms of fatty acid desaturase 1 (FADS1) were evaluated for associations with fatty acids in brisket adipose tissue of Canadian cross-bred beef steers. The polymorphism of 84 bp insert/deletion in intron 5 of SREBP1 was significantly associated with the concentration of 9c C17:1 (P=0.013). The G>A single nucleotide polymorphism (SNP) in the exon 4 of LXRα gene was associated with the concentration of 9c, 11t C18:2 (P=0.04), sum of conjugated linoleic acids (CLA) (P=0.025) and 11c C20:1(P=0.042). Two DNA polymorphisms in the promoter region of FADS1, deletion/insertion of ->GTG in rs133053720 and SNP A>G in rs42187276, were significantly associated with concentrations of C17:0 iso, C17:0 ai, total branched chain fatty acids (BFA), 12t C18:1, 13t/14t C18:1, 15t C18:1, and 13c C18:1 (P<0.05). Further studies are needed to validate the associations and to delineate the roles of the gene polymorphisms in determining the fatty acid composition in beef tissues.

DNA Damage and Transcriptional Changes in the Gills of Mytilus galloprovincialis Exposed to Nanomolar Doses of Combined Metal Salts (Cd, Cu, Hg)

[ENG]Aiming at an integrated and mechanistic view of the early biological effects of selected metals in the marine sentinel organism Mytilus galloprovincialis, we exposed mussels for 48 hours to 50, 100 and 200 nM solutions of equimolar Cd, Cu and Hg salts and measured cytological and molecular biomarkers in parallel. Focusing on the mussel gills, first target of toxic water contaminants and actively proliferating tissue, we detected significant dose-related increases of cells with micronuclei and other nuclear abnormalities in the treated mussels, with differences in the bioconcentration of the three metals determined in the mussel flesh by atomic absorption spectrometry. Gene expression profiles, determined in the same individual gills in parallel, revealed some transcriptional changes at the 50 nM dose, and substantial increases of differentially expressed genes at the 100 and 200 nM doses, with roughly similar amounts of up- and down-regulated genes. The functional annotation of gill transcripts with consistent expression trends and significantly altered at least in one dose point disclosed the complexity of the induced cell response. The most evident transcriptional changes concerned protein synthesis and turnover, ion homeostasis, cell cycle regulation and apoptosis, and intracellular trafficking (transcript sequences denoting heat shock proteins, metal binding thioneins, sequestosome 1 and proteasome subunits, and GADD45 exemplify up-regulated genes while transcript sequences denoting actin, tubulins and the apoptosis inhibitor 1 exemplify down-regulated genes). Overall, nanomolar doses of co-occurring free metal ions have induced significant structural and functional changes in the mussel gills: the intensity of response to the stimulus measured in laboratory supports the additional validation of molecular markers of metal exposure to be used in Mussel Watch programs

Preprocess and data analysis techniques for affymetrix DNA microarrays using bioconductor: a case study in Alzheimer disease

DNA microarray, or DNA chip, is a technology that allows us to obtain the expression level of many genes in a single experiment. The fact that numerical expression values can be easily obtained gives us the possibility to use multiple statistical techniques of data analysis. In this project microarray data is obtained from Gene Expression Omnibus, the repository of National Center for Biotechnology Information (NCBI). Then, the noise is removed and data is normalized, also we use hypothesis tests to find the most relevant genes that may be involved in a disease and use machine learning methods like KNN, Random Forest or Kmeans. For performing the analysis we use Bioconductor, packages in R for the analysis of biological data, and we conduct a case study in Alzheimer disease. The complete code can be found in https://github.com/alberto-poncelas/ bioc-alzheimer

Phosphorylation of the carboxy-terminal domain of histone H1: effects on secondary structure and DNA condensation

Linker histone H1 plays an important role in chromatin folding. Phosphorylation by cyclin-dependent kinases is the main post-translational modification of histone H1. We studied the effects of phosphorylation on the secondary structure of the DNA-bound H1 carboxy-terminal domain (CTD), which contains most of the phosphorylation sites of the molecule. The effects of phosphorylation on the secondary structure of the DNA-bound CTD were site-specific and depended on the number of phosphate groups. Full phosphorylation significantly increased the proportion of -structure and decreased that of -helix. Partial phosphorylation increased the amount of undefined structure and decreased that of -helix without a significant increase in -structure. Phosphorylation had a moderate effect on the affinity of the CTD for the DNA, which was proportional to the number of phosphate groups. Partial phosphorylation drastically reduced the aggregation of DNA fragments by the CTD, but full phosphorylation restored to a large extent the aggregation capacity of the unphosphorylated domain. These results support the involvement of H1 hyperphosphorylation in metaphase chromatin condensation and of H1 partial phosphorylation in interphase chromatin relaxation. More generally, our results suggest that the effects of phosphorylation are mediated by specific structural changes and are not simply a consequence of the net charge.

New DNA based hybrid catalysis

46 p.

Cloning and analysis of laccases from acinetobacter baumannii isolates

Laccases (benzenediol : oxygen oxi doreductases; EC 1.10.3.2) are wide spread i n nature. They are usually found in higher plants and fungi (Thurston 19 94; Mayer and Staples 2002), but recently some bacterial laccases have also been found . The first laccase studied was from Rhus vernicifera in 1883, a Japanese lacquer tree, fr om which the name laccase was derived (Yoshida , 1883). These enzymes belong to the group of bl ue multi - copper oxidases (MCOs) . They usually contain four copper atoms located in three distinct sites. Each site reacts differently to light. The Type 1 (T1) site copper atom absorbs intensely at 600 nm and emits the blue light , the Type 2 (T2) site copper atom is not visible in the absorption spectr um and last, the Type 3 (T3) site has two c opper atoms and absorbs at 330 nm ( Santhanam et al . , 2011; Quintanar et al . , 2007 ) . The protei n structure acts as a complex ligand for the catalytic coppers, providing them the right structure where changes between the reduction states are thermodynamically possible (Dub é , 2008 ) . These enzymes oxidize a surprisingly wide variety of organic and inorganic compounds like, diphenols, polyphenols, substituted phenols, diamines and a romatic amines, with concomitant reduction of molecular oxygen to water (Thurston , 1

Biomimetic Cloning of Quantum Observables

We propose a bio-inspired sequential quantum protocol for the cloning and preservation of the statistics associated to quantum observables of a given system. It combines the cloning of a set of commuting observables, permitted by the no-cloning and no-broadcasting theorems, with a controllable propagation of the initial state coherences to the subsequent generations. The protocol mimics the scenario in which an individual in an unknown quantum state copies and propagates its quantum information into an environment of blank qubits Finally, we propose a realistic experimental implementation of this protocol in trapped ions.

Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage

The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starcevo Cris culture in Romania (Carcea, Gura Baciului and Negrilesti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelnita cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.