IDENTIFYING OF FILAGGRIN GENE MUTATION THROUGH SEQUENCE ANALYSIS

NIKESH.N

Sequence Alignment in

Bioinformatics

Presentation Agenda

• What is sequence alignment & Why ?• Principles of sequence alignment• Sequence algorithms/tools• Problem statement • Objective of the study• Filaggrin gene mutation• Current status• How ? Proposed methodology• Scope & Limitations• Benefits of the project• Scope for further research• Conclusion

What ? Why ?

• Way of arranging the sequences of DNA, RNA or protein to identify regions of similarity .

• Helps in inferring functional , Structural or evolutionary relationship between the sequence

• Sequence alignment methods are used to find the best- matching sequences

DNA Sequencing (Genetic code)

• To determine the nucleotides sequence of DNA. ( Adenine, Thymine, cytosine, Guanine )

Uses of sequencing

- it can be used to find genes, segments of DNA that code for a specific protein or phenotype

- If a region of DNA has been sequenced, it can be screened for characteristic features of genes.

Principles of Sequence

Alignment Alignment is the task of locating

“equivalent” regions of two or more sequences to maximize their similarity

NIKESH NARAYANAN (RED : Mismatches)NIGESH NARAYAN- - ( gaps )

Principles of SequenceAlignment

• Alignment can reveal homology between sequences

• Similarity is descriptive term that tells about the degree of match between the two sequences

• Sequence similarity does not always imply a common function

• Conserved function does not always imply similarity at the sequence level

• Convergent evolution: sequences are highly similar, but are not homologous

Scoring Alignments:The Main Principles

• Alignments of related sequences is expected to give good scores compared with alignments of randomly chosen sequences

• The correct alignment of two related sequences should ideally be the one that gives the best score

• In practice, the correct alignment does not necessarily have the best score, since no “perfect” scoring scheme has been devised

Percent Identity as a Measure forQuantifying Sequence Similarity

Identity is the number of identical bases or amino acids matched between two aligned sequences

Percent identity is obtained by dividing this number by the total length of the aligned sequences and multiplying by 100

Types of Alignment

Based on Completeness• Global• Local

Based on Numbers• Pair wise alignment

• Multiple sequence Alignment

Methods & Algorithms

Dot matrix MethodDynamic programmingProgressive Methods : Clustal, TCoffeeIterative MethodsMotive findingFASTABLAST

Problem Statement

Identifying of Filaggrin Gene Mutation through sequence Analysis and identical patterns for filaggrin proteins

Filaggrin

Filaggrins are filament-associated proteins which bind to keratin fibers in epithelial cells. which is normally found in large quantities in the outermost layers of the skin. This protein is essential for skin barrier function, helping to form a protective layer at the surface of the skin that keeps water in and keeps foreign organisms out.

2008;122:689-93

Filaggrin

Clinical significance

Individuals with truncation mutation in the gene coding for filaggrin are strongly predisposed to a severe form of dry skin, (ichthyosis vulgaris), and/or eczema.[1]

Another study showed that many people with ichthyosis vulgaris also have eczema. Further research then showed a link between ichthyosis vulgaris, eczema and asthma.

At least in a subset of those with asthma, the filaggrin gene defect may be the fundamental predisposing factor not only for the deve

lopment of eczema but also asthma

Objectives of the study

To detect faulty filaggrin gene which may cause Eczema & Asthma

To find out the identical human proteins which may have functional similarity with filaggrin

To find out same or identical proteins from other species which may be helpful in therapeutics

Current Status

Many studies have proved that mutation in filaggrin gene will cause deficiency/absence of filaggrin protein which may lead to eczema, Asthma etc.

Researches are going on to find out Medication/Gene therapy

Scope of proposed study

• Sequence analysis of infected person’s gene with healty gene

• Probable persons’ gene ( hereditary threat )

• Identical protein sequence

Methodology

• To identify filaggrin gene mutation

•Pair wise alignment

Methodology contd.

To find out identical protein sequence

multiple sequence analysis BLAST

Limitations

Practical difficulties in getting specimen.( not a funded project )

Expected benefits

Preventive measures for susceptible persons

therapeutic -Identify similar proteins which might have similar functions as that of filaggrin.

Plant & Animal proteins – Proteins identical with filaggrin in plants and animals can be utilized for protein supplements

Scope for further research

Finding Gene Therapy methods for Asthma/Eczema patients

Conclusion

Drugs or other treatments aimed at the filaggrin gene are still some years away but researches in this direction give hope to those with these distressing conditions. Hope this study will contribute for the right direction.