Facilitating Complex Trait Analysis via Reduced Complexity Crosses

Camron D. Bryant*, Desmond J. Smith, Kathleen M. Kantak, Thaddeus S. Nowak, Robert W. Williams, M. Imad Damaj, Eva E. Redei, Hao Chen, Megan K. Mulligan

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


Genetically diverse inbred strains are frequently used in quantitative trait mapping to identify sequence variants underlying trait variation. Poor locus resolution and high genetic complexity impede variant discovery. As a solution, we explore reduced complexity crosses (RCCs) between phenotypically divergent, yet genetically similar, rodent substrains. RCCs accelerate functional variant discovery via decreasing the number of segregating variants by orders of magnitude. The simplified genetic architecture of RCCs often permit immediate identification of causal variants or rapid fine-mapping of broad loci to smaller intervals. Whole-genome sequences of substrains make RCCs possible by supporting the development of array- and targeted sequencing-based genotyping platforms, coupled with rapid genome editing for variant validation. In summary, RCCs enhance discovery-based genetics of complex traits.

Original languageEnglish (US)
Pages (from-to)549-562
Number of pages14
JournalTrends in Genetics
Issue number8
StatePublished - Aug 2020


  • GWAS
  • functional variant
  • positional cloning
  • rat genetics
  • substrain, QTL

ASJC Scopus subject areas

  • Genetics


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