International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

Oral Presentation

Monday 18 November

21:45 - 22:00 HRS

MASSIVELY PARALLEL COMPLEX TRAIT ANALYSIS OF TRANSCRIPTIONAL ACTIVITY IN MOUSE BRAIN

RW Williams
University of Tennessee Health Science Center

Co-Authors: 2) Manly KF, 1) Shou S, 1) Chesler EJ, 3) Hsu HC, 3) Mountz J, 4) Threadgill DW, 1) Lu L
Institutions: 1) University of Tennessee Health Science Center, 2) Roswell Park Cancer Cancer Institute, 3) University of Alabama, Birmingham, 4) University of North Carolina, Chapel Hill NC

Variation in patterns of gene expression produces fundamental differences in the structure and function of cells, organs, and ultimately, individuals. Differences in transcript abundance have a sufficiently high heritability to map as complex traits. This makes it practical to simultaneously discover upstream QTLs that modulate expression of thousands of transcripts using microarrays. Expression levels of 12,422 transcripts were measured in triplicate using pooled forebrain samples from 24 isogenic RI lines of mice. Transcript variance was mapped using computationally efficient regression methods (Manly et al. this meeting). LOD scores above 4, 5, and 6, were achieved for 3500, 670, and 310 transcripts. These loci influence the expression of key CNS transcripts, including genes associated with neuronal excitability (Kcnab, Kcnj9, Gria2), memory (Camk2a, Grin2b), neuroendocrine and reproductive behavior (Chga, Smstr1, Sgne1, Freq, Avpr1a), circadian rhythm (Per3), axonal and vesicular transport (Kif1a, Vamp4), glial metabolism (Prkab1), and psychiatric and neurodegenerative diseases (Drd2, Drd4, Apba2). Transcript QTLs fall into one of three categories: 1. cis-acting loci that have very high LOD scores (>6) and that are tightly linked to the chromosomal location of the transcript itself; 2. trans-acting QTLs with moderately high LOD scores (>4) that can influence many hundreds of transcripts distributed across the genome; 3. isolated trans-acting QTLs. Transcriptome-QTL mapping can be applied to virtually any tissue or cell type.By exploiting isogenic recombinant lines it is possible to extend this study and to examine the architecture and malleability of transcriptional networks in numerous tissues under a wide variety of environments and treatments.