A Genomic Survey of Polymorphism and Linkage Disequilibrium

Imran Mohiuddin

Magnus Nordborg, Ph.D.

University of Southern California

Arabidopsis - It’s What’s For Research

Small genome - only 5 chromosomes. A. thaliana is believed to be at least 99%

selfing. High level of inbreeding has led to extensive

linkage disequilibrium. Inbreeding increases linkage disequilibrium

without greatly decreasing polymorphism.

General Research Interests

Genetic basis of adaptation. Genomic survey of polymorphism. Genetic basis of flowering time. Applicability of association mapping. Development of statistical methods for

analyzing genomic polymorphism data in context of evolutionary questions.

Genomic Survey of Polymorphism

Characterize a reference collection of 96 accessions.

Sequence 1500-2000 short fragments (500-700 bp) distributed throughout this collection.

Develop bioinformatics tools to make the polymorphism data available and useful for the scientific community.

Funded by the NSF 2010 Project.

Project Status

~1000 fragments have been processed and are available through the existing polymorphism tools.

15,000 tentative polymorphic markers are in queue for submission to The Arabidopsis Information Resource (TAIR).

My project was to create a utility that allows the Nordborg lab to analyze and refine polymorphism data before submitting to TAIR.

Arabidopsis Software Suite

Genome Viewer – View progress of overall sequencing effort.

Alignment Viewer – View and download aligned sequences of completed fragments.

Haplotype Viewer – View and download polymorphic sites in completed fragments.

Polymorphism Viewer – Tabulate and view all polymorphisms.

Why Study Polymorphism?

Increasing availability of genomic polymorphism data may allow linkage disequilibrium to be used in association mapping.

Extent of linkage disequilibrium determines density of the map required to detect associations.

Extent of linkage disequilibrium also controls how finely loci may be mapped.

About the Project – TAIR Viewer

I had no prior programming experience. It’s an Internet based viewer written in Perl. Uses DBI module, which allows interaction

with a separate mySQL database containing polymorphism information.

The CGI module generates new HTML displaying desired results.

How Does It Work

Feature List

My viewer provides the ability to form queries by: polymorphism type. “SNP” name. specific chromosome and position. polymorphism presence in various

combinations of the 96 accessions. polymorphism frequency.

Project Demonstration

Yes officer, this really is Arabidopsis…

Search by Location, Type, or Name

Search by Accession

Search by Allelic Frequency

Sample Results

More Sample Results

The Nordborg Laboratory

Located in the Ahmanson Center for Biological Research at the University of Southern California.

Part of the Center for Computational and Experimental Genomics.

Acknowledgements

Dr. Magnus Nordborg Chris Toomajian Chitiksha Shah and Rana Goyal Dr. Jamil Momand, Dr. Wendie Johnston, Dr.

Sandra Sharp, Dr. Warter-Perez Jackie Heras SoCal BSI Colleagues

Sources 1. Nordborg, M., Borevitz, J.O., Bergelson, J., Berry, C.C., Chory, J., Hagenblad,

J., Kreitman, M., Maloof, J.N., Noyes, T., Oefner, P.J., Stahl, E.A., and Weigel, D. (2002) "The Extent of Linkage Disequilibrium in Arabidopsis thaliana" Nature Genetics, 30:190-193.

2. Nordborg, M. (2000) "Linkage disequilibrium, gene trees, and selfing: An ancestral recombination graph with partial self-fertilization" Genetics, 154:923-929.

3. Cardon, L.R. & Bell, J.I. Association study designs for complex diseases. Nature Rev. Genet. 2, 91-99 (2001).

4. A genomic survey of polymorphism and linkage disequilibrium. http://walnut.usc.edu/2010