Role Of Apolipoprotein In Alzheimers Disease

Introduction

Alzheimers disease is the most common form of dementia, this disease is the fourth leading cause of death in industrialized nations, preceded by cardiovascular disease. Neurodegenerative disease (ND) is an umbrella term for a group of primary diseases of neuron with the defining feature of a progressive loss of functioning neurons, mainly in the cortex and hippocampus, during the process of learning and memory formation brain undergoes a physical and chemical change which called as synaptic plasticity, its shows contribution of various signal transfusion pathway induction of gene expression which result formation of new synapse between nerve cell, this process undergoes remodelling with time the memory of a new experience can we divided by three types- namely short term, long term memory. The process of memory formation involves the binding neurotransmitter to the receptor which triggers the cascade oh molecular events including action of CREB and PKc pathways, resulting in the formation of new protein receptor and some structural proteins, the synaptic connection between two repeatedly communicating neurons which ultimately result developed long term memory. Memory can be classified into declarative and non-declarative, declarative memory affords and capacity for cognizant recollection about fact and event, in declarative memory a heterogeneous collection nonconscious ability in include learning of skills and way of life, in these cases behavioral change, but without according access any memory content, and different kind of memory are supported by different brain system. This disease has provided significant path physiology, it affects all ethnic groups and occurs slightly more in female than males. Disease according to age like brain disorder in create symptoms such as confusion and memory loss and sometime after converted yet normal age in personality and behaviour changed and awareness decision and in creative problem among friends and family members in complete loss, form mental works functions because this disease related to a mutation in most cases of Alzheimer’s disease has mostly with 65 years old people. ApolipoEprotein is major genetic risk factor play the role of increased problem in Alzheimers disease, apolipoprotein is a cholesterol carrier for lipid transfer repair damage in brain, cause mutation responsible for amyloid precursor protein apolipoprotein located in chromosome 19 and encodes299 amino acid, extracellular plaques of insoluble beta-amyloid peptide and neurofibrillary tangles remaining hyperphosphorylated tou protein in neuronal cytoplasm is remarkable path physiological cause patients brain.

Glycoprotein and apolipoE single several nucleotide polymorphisms convert result in coding region of apoEprotein, there are three common different of apoE genes are called alleles apoE2, apoE3 , apoE4 this differ from 1 or 2amino acids these are most common Isoform . Every gene has one copy combination determine apoE, ApoE2 is rarest form of apolipoprotein decrease developing risk of Alzheimers disease, apoE3 is allele and apoE 4 allele is increase risk of Alzheimers disease. Genomicus is graphical browser in which analysis four different type species like as, plant, fungi, vertebrate, non-vertebrates and flowering plants in study development of genes organization. Full genome sequences are available in Gene Databank, without growth in genes visualization and alignment sequences in Bioinformatics tool to possible used in genome starting development time restricted from again a new synteny browser in analysis multiple genome sequences in can seen phylogenetic view and ancestral genome. Most of genome data displayed in Genomicus is already publicly available from the assembled database but without extensive synteny visualization tool, the two main types of information that are required by genomics are positional information in their respective genome and phylogenetic relationships between genes. Genomicus in edits Ensembl phylogenetic trees in three ways first duplication nodes with a duplication consistency score below a threshold, that optimize increase synteny between extent genomes are selected such cases duplication notes .second added ancestral nodes in existing trees of placental mammals third added extent species that are not currently referenced in Ensembl with their respective ancestral nodes for each of new species.

ApolipoE protein-

ApolipoEprotein plays an important role distribution and metabolism of cholesterol triglyceride, E2, E3, E4 remains 112 and 158 ApoE3 is cyst112, Arg158. ApoE4 is arginine and ApoE2 is cystein, in lipid effect cause properties and three dimensional structures between isoforms. ApoE4 has substituted of amino acid with salt bridge formation between arginine and glutamic acid in arginine position is 61, n-terminal domain and glutamic acid position in 255, c-terminal of apoE4 Bind ApoE3 and ApoE2 protein in high density lipoproteins, anionic carboxylate of gluttamic acid and cationic ammonium of arginine remain with ionizable side chain as histidine, tyrosine and serine can take a part, depend on external factor. Formation of amyloid beta fibrils and oligomers need a conformational change from alpha helix two beta-sheets, which occurs due to formation of a salt bridge. ApolipoEprotein important role is maintenance, repair and reorganization according to neurons, produce cholesterol and improve synapse develop in central nerves system. Apolipoprotein transfer lipid and damage repair in brain and alleles are genetic determinants, allele 4 has increased carry risk for individual but compare to allele 2 and allele 3 decreases the problem. Apolipoprotein bind to lipids in several cell surfaces. Hydrophobic Amoyloid beta peptides lead to synaptic neurodegeneration in Alzheimer disease.

Genomics tool –

Genomicus in genome data stored in available Ensemble Database, comparative genomics in study of evolutionary genes, genomics in new synteny browser can represent and compares a number of genomes rebuilding ancestral in syntenic blocks describe procedures details and comparative genes between available genome sequences, Genomicus database in analysis data of two different genomes of differ species by help of different type tool such as- matrix view, compute synteny block in phyldiag view, can alignment of different comparative genes .

Phyloview-Align view-

In selected apolipoE gene center display in 15 neighbouring genes like paralogs and orthologs on both side are known as about to genes. Gorilla species in orthologs or paralogs are shown by matching colours. Align view in reference genes alignments between Genes are present with genomic region Identify genes are belonging from same family. Genomicus is provided a comparison of pair wise genome interface in karyotype view according to colour of chromosomes cause syntenic, can rebuild of ancestor gene.

Phylodiag view in synteny blocks-

Comparison pairwise whole genomes provide by Genomicus representation with dot plot matrix, between two species in orthologs relationship relies extracted from apolipoE gene. Users allow preservation between two genomes global map in display. In representing segment by the diagonal line in between genomes no quantification degree of synteny. Phildiyag in allows to user compared for select two species as (ancestral and extent), phyldiyag display parameter in present chromosomes displayed gap for permit in synteny blocks. In synteny available, two selected different species in shows result two different colours by plot sinteny blocks. Only display phyldiyag views in genes are belonging from individual synteny blocks. Align view in displayed orthologs between human and gorilla.

Phyldiag view

Karyotype view-

Karyotype is process of pairing and ordering all chromosomes of an organism, thus providing a genome-wide snapshot of an individuals chromosomes. Karyotypes are prepared using standardized staining procedures that revel characteristic structural features for each chromosome. Clinical cytogeneticistis analysis human Karyotypes to detect gross genetic changes, -anomalies involving several mega bases or more of DNA. Karyotypes can revel changes in chromosome number in associated with aneuploid conditions, such as trisomy 21 (Down syndrome) careful analysis of Karyotypes can also revel more subtle structural changes, such as chromosomal deletions, duplications, translocations or inversions, in fact, as medical genetics become increasingly integrated with clinical medicine, karyotypes are becoming a source of diagnostic information for specific birth defects, genetic disorders.

Karyotype view and multikaryotype view

Experimental Method

Firstly go to homepage of Genomicus Database , in an analysis of data evolution gene sequences alignment Of different species .
Then search box in enter the reference ApoE (ENSGGoG0000006377) gene name and species name gorilla.
After search open phylo view can seen phylogenetic tree by help ancestral gene, by differ type colour shows nodes, can known query about genes.
Then after can seen in align view in alignment of genes, ancestral chromosomes, duplication, protein similarity, dN/dS ratio, Karyotype view, multi karyotype view in shows between human and gorilla gene, known physical length-100 and number of chromosome-40.
Comparisons genes can see matrix view and synteny blocks in phyldiag view, by alignment in genes of reference species.
Analysis of comparative genes can see alignment of different species genes by use of genomicus tool.

Authors comments: Draft in provide outline of topics in discussed proposal for research project. Method section elaborated upon clearing certain doubts on Bioinformatics used. Documents in more aspect timeline will be presented details of document in figures tube added introduction part which describe about to Alzheimers disease, ApolipoEprotein, and Genomicus browser. Thanks you. ****

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