International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

RECOMBINANT INBRED INTERCROSS (RIX) MAPPING: A NEW APPROACH EXTENDING THE POWER OF EXISTING MOUSE RESOURCES

David Threadgill
University of North Carolina
Dept of Genetics, CB#7264
Lineberger Rm 11-109
Chapel Hill NC 27599 USA

Co-Authors: 1)Threadgill D 2) Airey DC, 2) Lu L, 3) Manly KF, 2) Williams RW
Institutions: 1)Dept of Genetics, University of North Carolina at Chapel Hill, 2)Center of Genomics and Bioinformatics, University of Tennessee, 3)Dept of Molecular and Cell Biology, Roswell Park Cancer Institute

RIX mapping is a new complex trait mapping method that extends the power of existing RI strains. RIX mapping involves generating F1 hybrids by intercrossing all, or a subset of, parental RI strains to generate a genetically complex, but reproducible population of n(n-1)/2 unique individuals, where n is the number of parental RI strains. We have performed a theoretical analysis by simulating the mapping of QTLs using actual CXB and BXD genotypes. Furthermore, we have empirically validated the RIX approach using all 13 CXB parental strains, 78 non-reciprocal F1 RIX hybrids, and 4 reciprocal RIX hybrids to detect and map genes controlling body weight. RIX mapping has many significant advantages over existing mapping populations including: 1) greatly increased power to detect QTLs, particularly those with complex epistatic interactions; 2) improved mapping resolution; 3) mapping of additive, dominance, and epistatic effects; 4) analysis of multiple identical heterogeneous genomes minimizes non-genetic variance; 5) no genotyping is required; 6) data are cumulative enabling multivariant approaches; 7) parental effects can be mapped through analysis of reciprocal RIX crosses; and 8) phenotypic variances are smaller than inbred genomes. The major disadvantages of RIX mapping include: 1) a paucity of parental RI strains; and 2) existence of strong statistical association between non-syntenic chromosomal intervals in RI strains.