...Introduction World Economic Forecast. According to the World Economic Forum 2014, leading financial experts told participant that that the global economy was cautiously optimistic. Even though the global economic activity has strengthened; and global growth is expected to be 3.7 percent in 2014 and 3.9 percent in 2015, old risks are still present and the coming years might bring volatility. Therefore how governments plan to recover from the economic meltdown might determine whether there will be inflation or deflation. In emerging economies exports are the main drivers of growth activity; demand of goods from the advanced economies will lead to growth although domestic conditions may also interfere with the growth. Although many emerging markets have started to benefit from increased external demand their domestic growth has been slower than expected, this has been attributed to political uncertainty, policies and bottlenecks, which has affected investments negatively. These countries include Brazil, Russia, Middle Eastern countries and North African Countries. (World Economic Outlook Update, January 2014) In the U.S, federal budget deficit has fallen and banks are recapitalizing and working off bad loans. There will be no additional fiscal austerity at the federal, state and local government level meaning that there will be no budget cuts, spending will likely remain the same or go up stimulating the economy, and accelerating GDP from an average of 2.2 in the last four years...
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...www. .uni-rostock.de Bioinformatics Introduction to genomics and proteomics I Ulf Schmitz ulf.schmitz@informatik.uni-rostock.de Bioinformatics and Systems Biology Group www.sbi.informatik.uni-rostock.de Ulf Schmitz, Introduction to genomics and proteomics I 1 Outline www. .uni-rostock.de Genomics/Genetics 1. The tree of life • Prokaryotic Genomes – Bacteria – Archaea • Eukaryotic Genomes – Homo sapiens 2. Genes • Expression Data Ulf Schmitz, Introduction to genomics and proteomics I 2 Genomics - Definitions Genetics: www. .uni-rostock.de is the science of genes, heredity, and the variation of organisms. Humans began applying knowledge of genetics in prehistory with the domestication and breeding of plants and animals. In modern research, genetics provides tools in the investigation of the function of a particular gene, e.g. analysis of genetic interactions. Genomics: attempts the study of large-scale genetic patterns across the genome for a given species. It deals with the systematic use of genome information to provide answers in biology, medicine, and industry. Genomics has the potential of offering new therapeutic methods for the treatment of some diseases, as well as new diagnostic methods. Major tools and methods related to genomics are bioinformatics, genetic analysis, measurement of gene expression, and determination of gene function. Ulf Schmitz, Introduction to genomics and proteomics I 3 Genes ...
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...studied as a candidate for the HPE locus (7q36) (Roessler et al., 1996). SHH contains 3 exons, these exons were extensively researched in order to determine their role in HPE by Roessler et al. Exons were primarily studied because of their role in expression and to determine whether there were any significant mutations in any of the exons. Five mutations were found in autosomal dominant HPE (ADHPE) families (Nanni, 1999). On exon 1, 2 mutations were found. Exon 1 encoded the first 100 amino acids of the pre-protein and contained many highly conserved motifs. A mutation that was found in ADHPE 10 was in Gly31Arg. The mutation was a missense mutation resulting in a (GGG to AGG) change. The mutation was in a highly conserved residue and was next to the putative signal cleavage site. This could be a particularly significant site for the mutation to occur at because of the importance of the signal cleavage site. The signal cleavage site plays a large role in expression and if there is disruption at such a site, it could lead to a marked reduction in expression. Another mutation found on exon 1 was a nonsense mutation. It was present in ADHPE 6 at Gln100, the mutation caused a (CAG to TAG) change. This early termination of protein expression could implicate the role of reduced SHH leading to HPE. Exon 2 encoded 87 amino acids of the mature SHH-N protein and Roessler et al. found 3 mutations in this exon. One of these mutations was a nonsense mutation at ADHPE 14 at Lys105, causing a (AAG...
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...next to each other in each exon. All 5V probes contain primer sequences Y and all 3V probes contain primer sequences X. The probes will be ligated after they have annealed to the target sequences and then amplified using a single primer set with primers binding to the respect sequences. A stuffer sequence of variable length is included in the X-probe to discriminate between PCR fragments amplified from the different exons. Besides that, if a part of an exon containing one or both probe sequences is deleted that means the two exon-specific probes are not ligated. Next, the exon-specific PCR fragments will be separated by electrophoresis. The different amount of PCR products is quantitated and normalised by dividing the peak heights by combining the peak height of all peaks in that capillary. As a result, a theoretical value of 1 indicates that a heterozygosity for a deletion has been detected, meanwhile a theoretical value of 2 indicates that a wild-type sequence has been detected. A study proved that MLPA is an effective method to detect deletions or duplications of LDL receptor gene in FH (Oystein et. al 2005). Deletion of exons detected by MLPA c) Breast cancer A massive parallel pyrosequencing test can be used to analyse the BRCA1 and BRCA2 genes. The DNA samples were taken from patients who characterised with BRCA1 and BRCA2 mutations and polymorphisms. First, the PCR amplication has to be performed to amplify all the BRCA2 and BRCA2 coding exons in 97 amplicons. Then,...
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...the alternative splicing of CD45 gene alters in the production of different mRNAs that further produces different proteins (polypeptide chains). Thus, the difference in the production of functional protein (tyrosine phosphatase protein) has played the role in the regulation of development and maturation of T-cells, a lymphocyte cell. The difference in the production of tyrosine phophatase protein is due to the variation in alternative splicing of exon 4, 5 and 6 of CD45 gene in T-cells. Multiple signaling pathways that are induced by antigen signaling in turn regulate the alternative splicing. Some of the multiple signaling pathways that Dr. Lynch had mentioned are RAS (G-protein), Glycogen Synthase Kinase-3 (GSK-3) and c-Jun (c-Jun N-terminal Kinase or JNK) signaling. However, Dr. Lynch had illustrated the GSK-3 and JNK signaling pathway. In GSK-3 signaling, PSF is phosphorylated. PSF usually binds to the Exon splicing silencer (ESS) and plays the role in skipping of those exons or silencing of the expression of that particular exon during alternative splicing. Under the resting conditions of T-cells, the PSF is phosphorylated at Threonine 687. The phosphorylated PSF will undergo the conformation change. Thus, the altered conformation of PSF will be recognized by TRAP-150 protein and...
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...Multiple Sclerosis is an autoimmune disease as a response to the attack of the T-cells from the bloodstream on the central nervous system causing damage to the myelin sheaths of the CNS nerves leading to the formation of scar tissue known as sclerosis that prevents nerve impulses from traveling to and from the brain and spinal cord. MS is a result of the interactions between the mutated gene DDX39B and the gene IL7R. The DDX39B gene regulates the protein expression by splicing the IL7R exon 6; however, when the gene is mutated, the variant C allele enhances alternative splicing of IL7R exon 6, leading to the production of soluble sIL7R or the mutated form of IL7R. To determine the effects of the DDX39B gene, the DDX39B expression was suppressed...
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...Current Applications of Genetic Technology in Predisposition Testing and Microsatellite Instability Assays By Marsha L. Frazier, Li-Kuo Su, Christopher I. Amos, Patrick M. Lynch From the Departments of Epidemiology, Gastrointestinal Medical Oncology and Digestive Diseases, and Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Address reprint requests to Marsha L. Frazier, MD, Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; email mlfrazier@notes .mdacc.tmc.edu. INTRODUCTION IT IS POSSIBLE TO test selected subjects for germline mutations in genes causing familial adenomatous polyposis (FAP),1 hereditary nonpolyposis colorectal cancer(HNPCC),2-8 Peutz-Jeghers syndrome,9,10 and juvenile polyposis.11-13 Because the genes that are mutated in familial colorectal cancer syndromes can be mutated at a variety of different locations, assays for mutation detection are not simple. Many different approaches to mutation detection have been described in the literature, some of which are also described here. Specific strategies for testing are also discussed. THE BASICS Isolation of DNA and Polymerase Chain Reaction (PCR) DNA or RNA for genetic testing is almost always isolated from peripheral-blood leukocytes. This requires that the blood be drawn in tubes containing some sort of anticoagulant. The preferred anticoagulants are either citrate or EDTA. The cells are lysed...
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...It has been suggested that alternative splicing plays a forefront role in creating a complex collection of expressed sequences (mRNA) from a smaller number of genes in humans. In fact, Walter Gilbert had expressed that a variety of mRNA isoforms of one gene arises from different combinations of exon-splicing known as alternative splicing (Modrek & Lee, 2002). Alternative splicing can be classified into several types, with each type being different among species. Exon skipping is a type wherein a cassette exon and its bordering introns are spliced out of the transcript. This type is prevalent in higher eukaryotic forms. Two other types of alternative splicing are alternative 3’ splice site (3’ SS) and 5’ SS selection in which two or more splice sites are identified at one end of an exon. These two types account for a small percentage of alternative splicing in higher eukaryotes. Another type of alternative splicing is intron retention, characterized by an intron persisting in the mature mRNA transcript. It is the rarest type of alternative splicing in both vertebrates and invertebrates, but the most prevalent in plants, fungi, and protozoa (Keren et al., 2010). In the wake of discovering these alternative mRNA forms that diversify protein functions of the same gene, there, however, exists a problem of how to differentiate truly functional forms from those that are not, biologically or otherwise, which further opens up an avenue towards the risk of outright designating a discovered...
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...Dear Author Here are the proofs of your article. ·You can submit your corrections online, or via e-mail. · For online submission please insert your corrections in the online correction form. Always indicate the line number to which the correction refers. · You can also insert your corrections in the proof PDF and email the annotated PDF. · Remember to note the journal title, manuscript number, and your name when sending your response via e-mail. · Check any questions that have arisen during copy editing or typesetting and insert your answers/corrections. ·Check that the text is complete and that all figures, tables and their legends are included. Also check the accuracy of special characters, equations, and additional files if applicable. Substantial changes in content, e.g., new results, corrected values, title and authorship are not allowed without the approval of the responsible editor. In such a case, please contact us for futher advice. · If we do not receive your corrections within 48 hours, we will send you a reminder. · The final versions of your article will be published around one week after receipt of your corrected proofs. Jaworek et al. Orphanet Journal of Rare Diseases 2012, 7:44 http://www.ojrd.com/content/7/1/44 1 2 3 4 5 6 7 RESEARCH Open Access Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population Thomas J Jaworek1, Tasleem Kausar2, Shannon M Bell1, Nabeela Tariq2...
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...Irinotecan Camptothecin analogs were developed in the 1990s to prevent the solubility problems associated with camptothecin, a cytotoxic agent developed as an anticancer agent in the early 1970s. Camptothecin and its analogs inhibit DNA tropoisomerase I eventually preventing DNA re-ligation leading to the failure of replication machinery. [1-4] Irinotecan (also known as CPT-11) is one of the analogs approved for first-line therapy of advanced colorectal cancer in combination with 5-fluorouracil and/or leucovorin. In addition, irinotecan has also been used with cisplatin as a combination therapy for other cancers, such as lung and ovarian [5–6]. The major limiting factors of irinotecan are diarrhea and neutropenia that can range from severe...
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...letters to nature and 10 Na3HP2O7. FV solution also contained 0.2 NaF and 0.1 Na3VO4. Rarely, irreversible current rundown still occurred with FVPP. The total Na+ concentration of all cytoplasmic solutions was adjusted to 30 mM with NaOH, and pH was adjusted to 7.0 with N-methylglucamine (NMG) or HCl. PIP2 liposomes (20–200 nm) were prepared by sonicating 1 mM PIP2 (Boehringer Mannheim) in distilled water. Reconstituted monoclonal PIP2 antibody (Perspective Biosystems, Framingham, MA) was diluted 40-fold into experimental solution. Current–voltage relations of all currents reversed at EK and showed characteristic rectification, mostly owing to the presence of Na+ in FVPP and possibly also residual polyamines. Current records presented (measured at 30 C, −30 mV holding potential) are digitized strip-chart recordings. Purified bovine brain Gbg29 was diluted just before application such that the final detergent (CHAPS) concentration was 5 M. Detergent-containing solution was washed away thoroughly before application of PIP2, because application of phospholipid vesicles in the presence of detergent usually reversed the effects of Gbg; presumably, Gbg can be extracted from membranes by detergent plus phospholipids. Molecular biology. R188Q mutation was constructed by insertion of the mutant oligonucleotides between the Bsm1 and BglII sites of pSPORT– ROMK1 (ref. 11). A polymerase chain reaction (PCR) fragment (amino acids 180–391) from pSPORT–ROMK1 R188Q mutant was subcloned into pGEX2T...
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...Examination of FGFR2 is crucial for determining a diagnosis. Any type of mutations to the seventh exon, the section of a gene that amino acids are coded from, total up ninety-eight percent of all those affected by Aperts. The remaining two percent of the affected by the syndrome are a result from a genetic change of the ninth exon. These exons must be examined to determine whether one is living with the syndrome. The other way Aperts can be diagnosed is through clinical observations. Findings such as syndactyly, polydactyly, and a cone-shaped head also called Turribrachycephalic, which can be affirmed by a X-ray or CT scan. Other iconic facial characteristics such as superficial eye sockets, exophthalmos, ocular hypertelorism, underdeveloped jaw and/or center of the face, and a beak nose. With these characteristics solely Aperts syndrome can be diagnosed without the need of genetic testing, however can be confirmed through genetic examination (Genetic and Rare...
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...to visualize the mutation at a chromosomal level, as both wild-type and eyeless flies looked similar. The experiment involved electrophoresis and Polymerase Chain Reaction (PCR) through which we were able to isolate and amplify the needed DNA eyeless DNA. The difference between the wild-type Drosophila melanogaster and the eyeless Drosophila melanogaster is approximately only 500-nucleotide base pairs. As we see the eyeless phenotype is approximately 3000 base pairs in length while the wild-type phenotype is approximately 2500 nucleotides base pairs in length, a difference of about 500 base pairs. After completing nucleotide sequencing and comparing our data on the blast website, we determined that the eyeless mutation has being interest exons two and three, but more specifically the mutation itself was located within the second intron at base pairs 8264 to 9212. Introduction In the early 20th century scientists had already been acquainted with chromosomes, yet the correlation between genes and heredity was still unknown. Many scientists believed that genes were located on chromosomes, but lack that scientific evidence to prove this theory. Thomas H. Morgan an American biologist along with his student at Colombia University discovered a particular eye color mutation in the Drosophila melanogaster. (1) Morgan was able provide...
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...Chapter 6 Blast program for sequence comparisons and blast p-values- test whether 2 or more sequences (protein or DNA) share a common evolutionary origin (p >10^-3 = due to chance) Lack of relationship between number of genes in a genome and its biological complexity 10-nm versus 30-nm chromatin fibers – condensed chromatin= 30nm wide, “beads-on-a-string” =10nm wide nucleosome core histone composition (2 each of H2A, H2B, H3, and H4) – Histones exists as octamers. Core is wrapped by 147 bp, about 2turns of DNA= CONSERVED IN ALL EUKARYOTES two turns of DNA around histone core (147 bp) variable size of DNA between nucleosomes (15-90 bp) – depends on species structure of 30 nm fiber and role of H1 histone – resting chromatin will be 30nm wide, H1 binds where DNA enters and exits nucleosome core histone tail modifications (acetylation, methylation, phosphorylation) – methylation & DEacetylation condensing of chromatin (30nm) acetylation DE-condensing of chromatin (10nm) phosphorylation & ubiquitination chromatin remodeling euchromatin versus heterochromatin chromosome scaffold – hold the 30nm chromatin loops attached, genes far apart on the chromosome are close at the base of the loops called SARS (Scaffold Associated Proteins) width of fully condensed metaphase chromosomes (500-750 nm) – 500-750nm wide chromosome banding and FISH (fluorescence in situ hybridization) – identification of karyotypes (chromosome composition) allows painting of each...
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...N I N E In Cold Blood: The Tale of the Icefish In all things of nature there is something of the marvelous. -Aristotle It was a long way just to go fishing. The us-foot converted wooden sealing boat Norveg/a put to sea out of Sandcford Harbor, Norway on September 14,1927. Its primary destination was perhaps the most remote piece of land on the planet. Tiny Bouvet Island, a speck in the vast Southern Ocean, lay more than six thousand miles from Norway, sixteen hundred miles from the tip of Africa, and more than three thousand miles from South America. In the mid-1920S, commercial invention whaling was booming. The Norwegian of factory ships allowed greater numbers of animals to be taken without relying on shore facilities. Finding new stocks of whales was a priorHCllRE 9.1 The Non'egia a/ Bouvet Island. Photo (rom F;1I1gstOg Forskning r Sydish,lVct by Bjame Aagaard, Volume "N)le Tider." Published bv Cyldelldai Norsk Foriag, Oslo. 1930. ity for the entrepreneurs 2, who went to sea, and establishing tory and w.llers was a priorit) for the countries government claims to terri- involved. The Norwegian wanted to stake a claim to this icc-covered volcanic rock with 167 168 PART IV EVOLUTION IN ACT CHAPTER ON FIGURE 9.2 DitlefRlIstad 011 the Norvegia foredeck. Photo from Fangst Og Forskning I Sydishavet h)' 13,Clme i\C1gclClrd,volume "Nye Tider." Published by Cyldendal Norsk Forlag, Oslo, 1930. 9 ...
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