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It is very useful to explore the information of linked variants and their associated annotations [ 11 ]. Most of these DNA structural polymorphs have already shown there in vivo existence and may further be responsible for controlling gene expression. Genome-wide association studies GWAS have newly been added to this field for studying the molecular processes at the gene level [ 16 ]. Exponential growth in the biological data obtained from various bioinformatics tools enhanced our understanding of role of genetics in human health by facilitating our basic knowledge of disease and its related mechanisms.

It also, thereby improved and advanced the development of potential therapeutic strategies. Hence, genome editing has been explored for its potential not only for the treatment of monogenic disorders, but also for diseases which are infectious or have both genetic as well as environmental association. A summary of some of these bioinformatics databases and softwares has been elucidated in Figure 1 and some of these are briefly discussed in the following sections.

Summary of some bioinformatics tools utilized for the predicting the biological applications of nucleic acids and proteins [,50,51,54,]. Covering such a broad topic in a review was really impractical; hence this review had focussed only on an aim of discussing a few of the bioinformatics tools. This information may further be utilized in identifying the relevance of the structural polymorphs of the biopolymers in the regulation of gene expression and its related cellular processes.

Basic Local Alignment Search Tool BLAST The foremost indication about the characteristics of a freshly sequenced gene can be attained by sequence homology which is defined as comparison of a particular sequence with the sequences stored in a database. BLAST provides primary information about the nucleic acid or protein sequence before carrying out any biological studies.

It is employed to search an unknown sequence by performing sequence similarity with other sequences stored in a biological database at a very fast speed.

BLAST is a userfriendly program which helps in determining the nucleic acid as well as amino acid sequences. Megablast is used for faster determination of closely related matches, while Blastn is comparatively slow and used for diverged sequences [ 19 ]. Genomes of distinctive species can be searched in BLAST, which also has a nucleotide database constituting approx. It provides supercomputing ability to the computer, thus accelerating the use of parallel algorithms by researches.

BLAST has been coined as the most important bioinformatics tool which enables the researchers to understand the function of proteins and genes present in the genome.

Continuous improvement of BLAST website is in progress for developing more sensitive and fast bioinformatics tool for better and user-friendly search. Transcription is the primary and central point of regulating the gene expression [ 24 ].

Interestingly, all genes are not expressed in each and every cell. It depends on intricate mechanisms of transcriptional regulation determined by the interaction of specific proteins known as the transcription factors with the particular DNA sequences. Thus transcription factors are recognized as a key developmental regulator which explains the basis of gene expression, cell differentiation and homeostasis [ 25 ]. There are quite a few bioinformatics databases which can help us to identify transcription factor binding sites Figure 2.

Central Dogma of molecular biology describing the bioinformatics databases for assessing the regulatory units at transcriptional and translational level. Public release of this database is available at http: It was developed more than two decades ago to represent the basic interaction between transcription factors and DNA binding site. Over the years its contents and features have been advanced, altered and augmented.

A number of bioinformatics tools such as TESS http: It is accompanied by a web interface for searching and sub setting, an online utility for sequence analysis as well as a collection of programming tools for genome? It can be accessed via http: DNA-binding domain DBD is a database which browses through all the publicly available proteomes and speculates all the sequence-specific DNA-binding transcription factors TFs from them.

The current version of DBD consists of over proteomes. It provides genome-wide transcription factor predictions for organisms. Transcription factor predictions in this database can be accessed through http: MicroRNAs miRNAs control gene expression at the posttranscriptional level via annealing to transcripts of protein-coding genes, resulting in cleavage or translation inhibition of the target mRNAs [ 36 ] Figure 2.

Some databases like miRecords http: In addition, transcription factors and miRNA can work in a synergistic way or form feedback loops to regulate gene expression [ 39 ]. Evaluation of Genetic Variants DNA mutations are considered as potential targets to understand the functional role of specific genomic regions. Developing bioinformatics tools to understand DNA polymorphisms are proved to be a relevant area of research. Various algorithms and tools have been developed to retrieve a huge data from DNA mutation analysis.

Also, multiple DNA sequences can be analyzed at the same time [ 41 ]. Similarly, mutations found in proteins can be analysed using PMUT bioinformatics tool.

It can help in detecting disease-related mutations. This software gathers information from the local databases and then examines the polymorphism present in a particular protein [ 43 ]. Information about DNA repair mechanisms can be retrieved from REPAIRtoire database which provides data about the correlation between mutations found in genes and human diseases.

Genome-wide association studies GWAS furnish a huge data having genetic variants with familiar phenotypes. A confusing point regarding this type of study is linkage disequilibrium LD , which authorize multiple variants at the same locus to be affiliated with single phenotype [ 9 ].

HaploReg is a tool which is used for analyzing annotations of the non-coding genome at variants on haplotype blocks [ 45 ]. HaploReg annotation of GWAS has been used for haplotype fine-mapping and enrichment analysis [ 46 , 47 ]. Multiple Sequence Alignment Availability of vast amount of high-quality data for human as well as other large number of genomes has turned the interest of a lot of researchers towards comparing biological sequences DNA, RNA or protein from two or more genomes.

The fundamental procedure used for comparing is known as Multiple Sequence Alignment MSA and plays an essential role in exploring the highly conserved sub-regions among a set of biological sequences, thereby, identifying functionally or structurally important sites and understanding the evolutionary history of some species from their associated sequences [ 48 ].

The alignment of sequences is shown in the form of a matrix with each row denoting a single sequence. The aim of such alignment is to position the sequences in such a way that it contains the least number of mismatched nucleotides and place the homologous nucleotides in the same column while representing the insertions and deletions in the form of gaps [ 49 ].

Several widely used packages are available for MSA, e. Clustal is one of the oldest of the currently most widely used programs. Clustal Omega is the latest version of Clustal released in The web interface of Clustal Omega is available at http: It is considered better than other packages because of its lesser execution time, better quality and more accuracy. It permits the reuse of the previously used alignments and hence reduces recomputing time of the same alignment for second exercise.

New sequences can be made just by adding another set of sequences on the existing alignment itself. Each time you want to make a certain molecule, you must consult the book chromosome that has the correct instruction page DNA gene.

But you may be making many copies of your product in a short period, so one book might not be enough. You could keep many copies of each book, maybe thousands, but this would take up too much room. The LOC already covers 2. What if you needed copies of One Good Turn and interesting book about the history of the screw and screwdriver because at some time or another, people wanted to learn how to build a square screwdriver?

To avoid this need for extra space, you make copies of pages mRNA from the books chromosomes that can be taken out of the library nucleus and used for making the products. Each time you want a product, a translator tRNA and ribosome must be used. This converts the copied instructions mRNA into a usable product protein.

When one or several translations have been made, the copied instructions start to tear and get worn, and finally break down.

Good thing we still have the original copy of the book stored in the nucleus… I mean library. We can go back and make more copies later if we need them.

Humans are amateurs, we only have about 25, sets of instructions stored in 46 books, nowhere near the The central dogma of molecular biology says that DNA is replicated to DNA, so daughter cells get a full set of instructions. Finally, the mRNA acts as a code that is translated into an amino acid polymer — a protein. Retrotransposons laugh at HIV, as they can do all that and more. Just as there are many kinds of information storage at the LOC books, images, recordings, manuscripts, pamphlets, there are different kinds of nucleic acids as well.

We have talked about plasmids as extrachromosomal pieces of DNA that can code for genes, especially antibiotic resistance genes in prokaryotes. But the list of RNAs is far more impressive.

Of these, retrotransposons may be the most interesting. A transposon is a piece of DNA that can jump around from place to place in the chromosomes of a cell. Barbara McClintock won a Nobel Prize for identifying transposable elements were responsible for the different colors of corn kernels in maize.

Ancient viral RNA got inserted into plant and animal genomes. The retrotransposon can be transcribed to mRNA, and then could be reverse transcribed back into DNA or translated into protein. The DNA can then insert itself anywhere in the genome. The bottom cartoon shows HIV.

Since reverse transcription makes more mistakes than DNA replication, many more mutants can be produced. Retrotransposons use the library analogy to fill the shelves with hundreds of copies of themselves.

In and of themselves, retrotransposons represent an exception in nucleic acids. Transcription is the process of using DNA to produce an mRNA, so going the opposite direction is called reverse transcription. This is also what retroviruses like HIV do. In the case of retrotransposons, the chromosome held copies will be transcribed to an mRNA, and some of those copies might be translated into protein.

Other copies will be reverse transcribed back to DNA by an enzyme called reverse transcriptase and will insert themselves somewhere in the genome see picture. In this way, retrotransposons can make more copies of themselves and end up all over the chromosomes of the organism. Mutation occurs at a higher rate in reverse transcription than in DNA replication because reverse transcriptase makes more mistakes than replication enzymes. A study has investigated how one type of retrotransposon manages these different outcomes.

He goes through how fruit flies were recruited to disprove DNA heredity and ended up as the strongest evidence for it; how DNA is linked very strongly to linguistics and math; and how Stalin tried to breed a race of half human - half chimps. This is in addition to showing how most DNA on Earth is descended from viruses. One transcript mRNA is modified so it can be translated but cannot be reverse transcribed. The second transcript is packaged in small bundles to be reverse transcribed later back to DNA.

The third transcript type is smaller and actually houses the bundles of mRNAs to be reverse transcribed. So this retrotransposon balances itself between making protein and inserting itself into new places in the genome.

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