Abstract
The challenge of precision medicine is to model complex interactions among DNA variants, sets of phenotypes, and complex environmental factors and confounders. We have expanded the BXD family, creating a powerful and extensible test bed for experimental precision medicine and an ideal cohort to study gene-by-environmental interactions.
These BXD segregate for over 6 million variants, with a mean minor allele frequency close to 0.5. We have increased the family two-fold to 150 inbred strains, all derived from C57BL/6J and DBA/2J. We have also generated updated and comprehensive genotypes and an unrivaled deep phenome.
Approximately 10,000 recombinations have been located, allowing precision of quantitative trait loci mapping of ±2.0 Mb over much of the genome and ±0.5 Mb for Mendelian loci. The BXD phenome includes more than 100 ‘omics data sets and >7000 quantitative and clinical phenotypes, all of which is publicly available.
The BXD family is an enduring, collaborative, and replicable resource to test causal and mechanistic links between genomes and phenomes at many stages and under a wide variety of treatments and interventions.
Footnotes
Author email & ORCID David G. Ashbrook - dashbrook{at}uthsc.edu, Danny Arends - danny.arends{at}gmail.com, Pjotr Prins - jprins{at}uthsc.edu, Megan K. Mulligan - mkmulligan{at}uthsc.edu, Suheeta Roy - sroy12{at}uthsc.edu, Evan G. Williams - williams{at}imsb.biol.ethz.ch, Cathleen M. Lutz - cat.lutz{at}jax.org, Alicia Valenzuela - acv{at}jax.org, Casey J. Bohl - cbohl1{at}uthsc.edu, Jesse F. Ingels - jingels{at}uthsc.edu, Melinda McCarty - mmccarty{at}uthsc.edu, Arthur G. Centeno - acenteno{at}uthsc.edu, Reinmar Hager - reinmar.hager{at}manchester.ac.uk, Johan Auwerx - admin.auwerx{at}epfl.ch, Saunak Sen - sen{at}uthsc.edu - 0000-0003-4519-6361, Lu Lu - lulu{at}uthsc.edu, Robert W. Williams - rwilliams{at}uthsc.edu
Minor changes to figures, and full size versions of all figures now included in the pdf.
- List of abbreviations
- AD
- Alzheimer’s Disease
- AI
- advanced intercross
- B6
- C57BL/6J mouse strain
- BLAST
- Basic Local Alignment Search Tool
- BXD
- BXD family of recombinant inbred strains of mice, produced by crossing the B6 and D2 parental strains
- CC
- Collaborative Cross
- Chr
- Chromosome
- cM
- centimorgan
- D2
- DBA/2J mouse strain
- DO
- Diversity Outbred
- DX
- diallel cross
- EMRs
- electronic medical records
- eQTL
- Expression quantitative trait locus
- F2
- Filial generation 2
- GEMMA
- Genome-wide Efficient Mixed Model Association
- GigaMUGA
- Giga Mouse Universal Genotyping Array
- GN
- GeneNetwork (http://genenetwork.org)
- GN2
- GeneNetwork2 (http://gn2.genenetwork.org)
- GWAS
- genome-wide association study
- H2ix̅
- heritability of isogenic strain means
- H2RIx̅
- heritability of recombinant inbred strain means
- HMDP
- Hybrid Mouse Diversity Panel
- IMPC
- International Mouse Phenotyping Consortium
- JAX
- The Jackson Laboratory
- Kb
- kilobase
- KOMP
- Knockout Mouse project
- LOD
- logarithm of odds
- LRS
- likelihood ratio statistic
- Mb
- Megabase
- MMRRC
- Mutant Mouse Resource & Research Centers
- MUGA
- Mouse Universal Genotyping Array
- nRecP
- number of observed recombinations from one position to the next
- nRecS
- number of observed recombinations per strain
- PheWAS
- phenome-wide association studies
- QT
- quantitative trait
- QTL
- quantitative trait locus
- r2
- Coefficient of determination
- RI
- Recombinant inbred
- RIXs
- Recombinant inbred intercrosses
- SE
- Standard error of the mean
- SNP
- single nucleotide polymorphism
- UTHSC
- University of Tennessee Health Science Center
