Analyzing Phenotypic Variations and Polymorphism

Phillip TaoAdvisor: Professor Eleazar Eskin

Grad Student: Emrah Kostem

Polymorphism and SNP

• Polymorphism is a variation between the genome of two individuals or chromosomes

• Many types:– Deletion *– Duplication *– Inversion *– Single Nucleotide Polymorphism (SNP)

* These often cause major diseases, such as Cri du Chat and Charcot-Marie-Tooth disease, when large portions of the genome are affected [4]. However, their effect on small portions of the genome, (especially non-coding portions) have been mostly unstudied

Problem

• Polymorphisms can be used to identify disposition toward certain illnesses [1]

• Use mouse genome to identify problem causing alleles

• A lot of data to analyze, 8.27 million SNP in mice [2], estimated 10 million in humans [1]

• Very difficult to identify non-SNP polymorphisms– Can be very long, 1.5 million base pairs [3]

Past Methods and My Idea

• Polymorphism has been used to try to find causes for diseases such as cancer, etc. [5][6][7].

• They decided on a disease first, found an area of a genome they believe might influence the disease, then looked for polymorphisms in that area

• My way is to map the entire set of polymorphisms for a given genome (mouse genome), then look for correlations

Proposal, step 1

• Develop a way to identify non-SNP polymorphisms1. Find start of problem area2. Use marker sequence to find end of problem

area*3. Identify problem

* Idea borrowed from Restriction Fragment Length Polymorphism (RFLP)

Proposal, step 2

• Use Ruby to develop a tool to easily and flexibly model the data

• Develop algorithms to find correlation between polymorphisms and trait variations

Schedule

• A basic but functional version of the Ruby on Rails website should be finished, and a working but slow and inefficient version of the polymorphism finder should be done.

• By the end of Winter Quarter, the final version of the polymorphism finder should be finished, and a better version of the RoR website should also be finished

• By the end of the project, an algorithm should be found to analyze correlation between certain polymorphisms and trait variations

Resources1. http://www.usatoday.com/news/health/2005-02-17-gene-map_x.htm2. http://www.nature.com/nature/journal/v448/n7157/full/nature06067.

html3. http://www.nature.com/ng/journal/v29/n3/full/ng753.html4. http://en.wikipedia.org/wiki/Chromosome_abnormalities5. http://circ.ahajournals.org/cgi/content/abstract/

circulationaha;102/2/1976. http://jmd.amjpathol.org/cgi/content/full/8/4/4997. http://atvb.ahajournals.org/cgi/content/full/atvbaha;16/2/304