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					Predicting the Function of Single
Nucleotide Polymorphisms

       Corey Harada
       Advisor: Eleazar Eskin
Background

   Polymorphisms
       A change to a DNA sequence.
       Source of genetic variation.
   Single Nucleotide Polymorphism (SNP)
       Mutation of a single nucleotide.


           AGATCGATC
           AGATTGATC
Single Nucleotide Polymorphisms

   We can figure out the locations of
    SNPs by looking at genotypes.
       How do we figure out the function of each
        SNP?
           Many SNPs are do not affect phenotypes at
            all.
           A way to determine which SNPs are
            significant and which are not could be useful.
Approach

   Only work on SNPs in coding regions.
   Translate the protein using the
    sequence with and without the SNP.
   Use BLAST to find similar proteins.
BLAST

   Basic Local Alignment and Search Tool
   Searches a database of proteins for various
    organisms.
   Proteins in humans are related to those that
    other mammals produce.
       Finding better results for one SNP would
        indicate selection.
       May indicate that it is linked to a disease.
BLAST
   BLAST bit score
       Score S is based on how well the sequences
        align
       K – Scale factor for search space size
       λ – Scale factor for scoring system
   Bit score is the normalized score which
    indicates how well the protein aligns.
   Normalization is needed to compare scores
    for multiple alignments.
Results
   Based off of SNPs in exon regions of human
    chromosome 1 (from HapMap rel23a)
                90
                80
                70
                60
    Frequency




                50
                40
                30

                20
                10
                 0
                     0   100   200   300   400     500       600   700   800   900   1000
                                                 Bit Score
Analysis

   The program provided a number of
    SNPs with a zero difference in byte
    score, in some cases SNPs known to
    cause phenotypic changes.
   Possible causes:
       SNPs that cause changes to protein
        transcription.
Future Work

   Consider SNPs not in coding regions
       SNPs in introns could be ranked similarly
        based on binding data.

				
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posted:8/7/2012
language:English
pages:9