Predicting the Function of Single Nucleotide Polymorphisms Corey

Predicting the Function of Single Nucleotide Polymorphisms Corey Harada Advisor: Eleazar Eskin

Background n Polymorphisms ¡ ¡ n A change to a DNA sequence. Source of genetic variation. Single Nucleotide Polymorphism (SNP) ¡ Mutation of a single nucleotide. AGATC AGATTGATC

Single Nucleotide Polymorphisms n We can figure out the locations of SNPs by looking at genotypes. ¡ How do we figure out the function of each SNP? n n 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 n n n 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 n n n 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 n BLAST bit score ¡ ¡ ¡ n n 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 n Based off of SNPs in exon regions of human chromosome 1 (from Hap. Map rel 23 a)

Analysis n n 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 n Consider SNPs not in coding regions ¡ SNPs in introns could be ranked similarly based on binding data.