Single Nucleotide Polymorphism

Single Nucleotide Polymorphism SHREEVANI RAJ REDDY INTRODUCTION The aim of genetic research is to understand the role of genetic variation. In humans, the most common type of genetic variation involves single DNA bases, and is termed as single nucleotide polymorphism. DNA polymorphism involves one of two or more variants in a particular DNA sequence and Variation at a single base pair of DNA sequence results in single nucleotide polymorphism (SNPs). SNPs are the most common type of genetic variation among people; each SNPs represents a difference in single nucleotide. On average they occur once in every 300 nucleotide which means there are roughly 10 million SNPs in the human genome. These variations are commonly found in the DNA between genes. SNPs accounts for much of phenotypic diversity among individuals. In the human genome the half of the known coding region SNPs lead to change in the resulting amino acid sequences and other half do not, these are called synonymous SNPs. Synonymous SNPs encode change in the DNA sequence without altering the resultant protein sequence, these silent SNPs assumed as inconsequential, however these synonymous SNPs represent genetic marker for functional molecular alterations with which they are in linkage disequilibrium. These SNPs alters the function of gene and phenotype by various mechanisms such as altering protein folding, mRNA binding or by affecting splicing of mRNA; stability and expression of mRNA. These SNPs can act as biological markers (also known as gene marker), therefore helps to locate gene that are associated with disease. Researchers found that SNPs may help to predict an individuals response to certain drugs and susceptibility to environmental factors such as toxins and risk of developing particular disease. SNPs with sufficient technological solutions can enable the mapping of disease genes involved in complex disorders. One of the examples of mapping disease associated with SNPs is Alzheimer’s disease. GENETIC VARIATION Genetic Variation is defined as, variation of genomes between groups of species as a result of genetic mutations or genetic drifts. In all living organisms, the genetic material is made up of same basic components, called nucleotides. Each nucleotide contains one of four nitrogenous bases A (Adenine), G (Guanine), T (Thymine), C (Cytosine). These 4 building blocks are linked together to form long chains, the sequence of which then codes for various proteins and gene products. The DNA sequence collection and organization is specific for each species, and is called a genome. On average, two humans share 99% genetic identity, although the majority of differences in DNA sequence (genotype) do not result in noticeable physical change (phenotype), the few that account for the diversity in human population are height, eye, skin, hair color, etc. Mutation is the process of creating a new genetic variation. Mutation in a gene can arise from natural internal processes such as gene conversions, cell replications, meiotic recombination and also from number of environmental factors such as free radical damage caused by ingestion of toxins and radiations etc. FROM MUTATION TO POLYMORPHISM: In humans, every individual has two copies of genome each one copy originating from each parent. So in the genome at a given position, each individual has two copies of a particular sequence. Mutation causes a change in one DNA sequence, resulting in the individual having one copy of original sequence and second new sequence at mutation locus. If mutation occurs in somatic cells, then remains only in the individual in which mutation occurred, and if mutation occurs in germ cells (egg or sperm cells), then these genetic changes passes to offspring and thus are inheritable. This phenomenon termed as genetic drift, can act to either increase or decrease allele frequencies in the population. If mutant allele reaches to a frequency of 1% or more in population, then locus is said to be â€Å"polymorphic†. POLYMORPHISM TYPES â€Å"Polymorphism† is a Greek word meaning â€Å"having many shapes†. Therefore genetic polymorphism is easy to imagine that two strands of DNA that differ in sequence rather than shape. In human genome the most common types of polymorphism organized into the 3 classes:- Repetitive Elements:- In this type of polymorphism DNA sequences found in multiple copies throughout the genome. A classic example is ALU repeat (330 base pair in length), found in over 750,000 copies in genome. Another form of repetitive elements includes simple tandem repeat polymorphism (STRPs) or ‘microsatellites’. In this type of polymorphism, short di-, tri-, or tetra- nucleotide units are repeated consecutively at polymorphic position. Microsatellites are highly polymorphic, having up to 30 alleles and thus shows high allelic diversity and high heterozygosity Insertion and Deletion:- This type of di-allelic polymorphism is also known as indels. Presence or absence of one or more DNA bases at polymorphic position shows the difference between the allele. Substitutions:- This type of polymorphism are also most often di- allelic. Alleles of this type of polymorphism are distinguished by replacement of DNA bases, rather than presence or absence as in indels. SINGLE NUCLEOTIDE POLYMORPHISM This is a type of polymorphism in which alleles of these involve only single bases (OR type of polymorphism involving variation at a single base pair). SNP alleles can form by insertion or deletion of a single base or by substitution of one base for another. In case of substitution, the SNP alleles is limited to 4; Because DNA is made up of only 4 different nucleotide bases (A, T, G, C ), thus substitution of single nucleotide are at most tetra-allelic. However tetra-allelic or tri-allelic SNPs are very frequent with majority of true documented cases being in the mitochondrial genome, for this reason SNPs are thought of as di-allelic polymorphism. SNP alleles are created by transition (purine to purine /pyrimidine to pyrimidine) or transversion (purine to pyrimidine / pyrimidine to purine) substitutions. In the human genome 70% of all SNPs involve a Cytosine (C) to Thymine (T) transition. This is due to conversion of 5- methyl cytosine to Thymidine by deamination mechanism. SNPs are copying Errors: An existing cell divides in two to make a new cells, first it copies its DNA so the new cell each will have a complete set of genetic instructions. Sometimes cells make mistakes during the coping process, this leads to changes in the DNA sequence at a particular location, called SNPs. Chromosomal distribution of SNPs: Although some 3 million SNPs already in databases, this is only a fraction of 11 million SNPs thought to be present in the human genome. By comparing any two randomly chosen chromosomes, number of studies pointed that one SNP occurs in 1-2 kb of sequence in a genome. However SNPs are not distributed evenly down the length of any chromosome. The human chromosome contains large stretches of non-coding sequences with patches of coding sequences. Roughly the genetic variation is 4 times less in coding sequence than in non-coding sequences. Alteration in the certain sequences such as Exons, promoters, and enhancer sequence could adversely affect biological normal functions; therefore natural selection pressure would act to preserve certain sequences. However, there are few exceptions where coding sequence shows a high degree of polymorphism. For example, there is high sequence variability in and around the HLA genes, which encode for the important components of immune system. Many SNPs that occur in the exons, are in the wobble position of the reading frame, and thus not alters the protein sequence. This type of changes are thought to have no effect or little effect on the gene product and called as synonymous or silent substitutions. On the other hand non- synonymous variants, cause substitution of one amino acid for another at protein level. The consequence of this type substitution on protein function varies from no effect to total disruption of protein. The changes in most severe single base in the exon regions can produce shifts in open reading frame, or creation of stop codon, either which can cause copy of nonfunctional gene product. These types of non-synonymous variations if reach to a high frequency, then considered as polymorphism. Two additional regions of chromosome are Telomere (end region of chromosome, plays important role in aging) and Centromere (central region of chromosome, which plays a key role in cell division) known to be highly po lymorphic. DETECTION TECHNIQUE FOR SINGLE NUCLEOTIDE POLYMORPHISM SNPs are the positions in the genome where some individuals have one nucleotide and others have a different nucleotide. There are vast numbers of SNPs in every genome, some of which also gives rise to RFLPs, but many of which do not because the sequence in which they lie is not recognized by any restriction enzyme. In human genome there are at least 1.42 million SNPs, only 100000 of which results in an RFLP. Although each SNP could, potentially, have four alleles (because there are 4 nucleotides), most exist in just two forms, so these markers suffer from the same drawback as RFLPs with regard to human genetic mapping: there is a high possibility that a SNP does not display any variability in the family that is being studied. The advantages of SNPs are their abundant numbers and the fact that they can be typed by methods that do not involve gel electrophoresis. This is important because gel electrophoresis has proved difficult to automate, so any detection method that uses it will be relatively slow and labor-intensive. SNP detection is more rapid because it is based on oligonucleotide hybridization analysis. An oligonucleotide is a short single stranded DNA molecule, usually less than 50 nucleotides in length, that is synthesized in the test tube. These synthetic probes are also known as allele specific oligonucleotide (ASO). ASO can identify alleles that differ by single nucleotide. ASOs detect changes of all types of single nucleotide, including those that do not affect the restriction enzyme cutting sites. If the conditions are just right, then an oligonucleotide (ASO) will hybridize with another DNA molecule (with its complementary sequence not with other sequences) only if the oligonucleotide forms a completely base-paired structure with the second molecule. If there is a single mismatch – a single position within the oligonucleotide that dose not form a base pair, then hybridization does not occur. Oligonucleotide hybridization can therefore discriminate between the two alleles of an SNP. Various screening have strategies have been devised including DNA chip technology and solution hybridization techniques. SNPs as a genetic marker A SNP is a type of gene marker (DNA marker) with a single base pair alteration at a particular site in some individuals, that site is SNP locus. These DNA markers are detected by molecular analysis of DNA and can be used in genetic analysis. SNP loci found abundant in the human genome, on average about once in 1000 bp. The presence of abundance of SNP loci allowed researchers to develop detailed maps of location of SNPs on chromosome. ALZHEIMER’S DISEASE This is a complex degenerative brain disorder characterized by progressive cognitive decline and memory impairment. This disorder annually, afflicting about 2.5 millions Americans. It is the 4th leading cause of death among elderly Americans. In 1900 the German neurologist ALIOS ALZHEIMER, found this disease accompanied by organic loss of intellectual function (dementia) as well as memory loss and general incapacitation. Sufferers often cannot speak, walk or tent to do their most basic needs. In 1987, researchers at several institutions identified a specific gene inducing the brain tissue abnormality, which characterizes the malady. And then simultaneously another research team announced that it was using a DNA probe to locate a genetic marker for the disease on human chromosome 21. But these findings do not suggest that all cases of this disease are genetically linked, they indicate that at least one form of this disease (i.e. familial Alzheimer’s disease (FAD)) may be inheritable. The gene responsible for FAD abnormality appears for manufacturing a protein called amyloid. Amyloid is a major component of clumps of dead and dying nerve fibers that clog the brains of patients with Alzheimer’s disease. In some individuals this form of dementia acquire before the age of 65 ( refer to as early onset or FAD )but most often occurs late in life.

International Coach Federation Code of Ethics

International Coach Federation Code of Ethics International Coach Federation Code of Ethics Professional Conduct at Large #7 – I will maintain, store, and dispose of any records created during my coaching business in a manner that promotes confidentiality, security, and privacy, and complies with any applicable laws and agreements Professional Conduct with Clients 12 – I will not knowingly take any personal, professional, or monetary advantage or benefit of the coach-client relationship, except by a form of compensation as agreed in the agreement or contract. Professional Conduct with Clients #18 – I will not become sexually intimate with any of my current clients or sponsors. Confidentiality/Privacy and Conflicts of Interest. #22 – I will maintain the strictest levels of confidentiality with all client and sponsor information.I will have a clear agreement or contract before releasing information to another person, unless required by law It is very interes ting to learn that a coach and a teacher are very much alike in many ways, especially when it is about ethics. I learned also that the coach’s pledge is very similar to the teacher’s. As an ICF Professional Coach, I acknowledge and agree to honor my ethical and legal obligations to my coaching clients and sponsors, colleagues, and to the public at large.I pledge to comply with the ICF Code of Ethics, and to practice these standards with those whom I coach. If I breach this Pledge of Ethics or any part of the ICF Code of Ethics, I agree that the ICF in its sole discretion may hold me accountable for so doing. I further agree that my accountability to the ICF for any breach may include sanctions, such as loss of my ICF membership and/or my ICF Credentials. Reference International Coach Federation Code of Ethics. Retrieved from www. coachfederation. org/ethics/En  cache  Ã¢â‚¬â€œÃ‚  Similares

Ecco Sets Store Chain Management Standards in Russia

24/11/12 GMCS – ECCO sets store chain management standards in Russia using Microsoft Dynamics AX for †¦ C urrent page U RL: http://w w w . gmcs. ru/en/press/new s/4447/index. php Print this page HOME / PRESS-CENTER / NEWS / ECCO SETS STORE CHAIN MANAGEMENT STANDARDS IN RUSSIA USING MICROSOFT DYNAMICS AX FOR RETAIL Events 19 July 2012 News ECCO-ROS, an exclusive distributor of Danish shoe brand ECCO in Russia deploys Microsoft Dynamics AX for Retail in order to come to a new quality level of customer service, improve management performance and develop the retail store chain.This project is unique because for the first time based on Microsoft Dynamics AX for Retail, a uniform solution for the automation of geographically dispersed chain of the ECCO stores in Russia will be made to replace intermediate cash accounting software that is currently being used. This will enable ECCO-ROS to reduce costs for operation of the systems and management of the company as a whole, optimiz e business processes in the retail stores, improve merchandise flow management, and improve reliability of information flows inside the chain.In addition, the distributor expects to increase sales for the account of the offered Microsoft Dynamics AX for Retail expanded opportunities for marketing activity management, and implementation of a new customer loyalty bonus system the deployment of which will be supported by the implemented system. â€Å"Activities of ECCO-ROS are based on the ECCO reference models and general management principles, including the key principles – innovativeness and manufacturability.These ideas also find reflection in management of the IT-infrastructure of our company. Today, we implement a non-trivial project in Russia, and we believe that the implementation experience will be of interest in the retail business†, says Sergei Prokhorov, IT-Director at ECCO-ROS. â€Å"For instance, one of the features of the implemented solution is that we wi ll get an opportunity for complete synchronization of the POS-terminal operations even in case of absence of communication or failures in the communication channels.It is an important criterion for retail business†. GMCS is a project partner, a winner of the competitive tender for the implementation of the project on the automation of the ECCO-ROS retail chain, which expertise in the field of retail is presented by successful projects for the leaders of this market. One of the key decision-making factors in the selection of the partner was the quality of projects implemented by the partner, and the partner’s focus on customer satisfaction†, explained Sergei Prokhorov.At present, the GMCS specialists completed creation of a solution concept model for customer accounting and service. According to the proposed model based on Microsoft Dynamics AX for Retail, the following processes will be automated: acceptance, shipment, return, and selling, including selling of goo ds on credit and via ECCO Internet Shop, payment and cash services, product range and stock management, inventorying and adjustment of entries of stock changes under wrong heading, warehouse.The system will enable to control personnel performance including opening and closing of shift, strict accounting of labor hours of the employees through a biometric authorization system, as well as accounting of visitors. The auxiliary processes will also be automated such as accounting of corporate clothes and footwear, and consumable materials. Emphasis is placed on the automation of marketing activity processes and loyalty management program. Based on Microsoft Dynamics AX for Retail, the processes of management of advertising campaigns, handling of saving discount cards, bonus and gift cards will be automated. The final project objective is to create a conceptually new, innovative and scaling solution for retail that will be able to replace front office software (disconnected, as a rule) fo r integrated customer accounting and service system that will form a uniform information space from cashier to manager. The Microsoft Dynamics AX for Retail tools enable us to accomplish all tasks stated by a customer†, comment Sergei Kotov, Retail Solutions Department Director at GMCS. – â€Å"We specially focus on the quality of the future solution, simplicity and flexibility of its use.ECCO-ROS will be able to independently customize the system later in case of any change or occurrence of new business-processes thereby reducing costs for support and development of the system†. The system is scheduled to be put into operation in the pilot regions (stores in Moscow and Saint Petersburg) in December 2012. In future, the uniform customer accounting and service system is expected to be deployed in all remaining stores of the retail chain that is presented today by more than 300 stores in Russia, Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan and Uzbekistan.E CCO-ROS is an exclusive distributor of Danish shoe brand ECCO in Russia. Since 1991, the company offers to Russian consumers the world’s popular ECCO shoes. As at 2012, the ECCO chain comprises of more than 300 stores in Russia, Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan and Uzbekistan and continues to actively develop. The company’s office is located in Moscow; management of the proprietary stores in the regions and interrelation with regional partners is performed from the office. Back to list Feedback  © 1997 — 2010 â€Å"GMCS† All rights reserved. Made in agency www. gmcs. ru/en/press/news/4447/? print=Y 1/1

10 Facts About Acids and Bases