Abstract
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 language | English (US) |
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Pages (from-to) | 549-562 |
Number of pages | 14 |
Journal | Trends in Genetics |
Volume | 36 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2020 |
Funding
The authors acknowledge the following funding sources: R01DA039168 (C.D.B.), R01CA22160 (M.I.D. & C.D.B.), U01DA041602 (D.J.S.), U01DA047638 (H.C. and R.W.W.), U01AA016662 (R.W.W.), and P30DA044223 (R.W.W. and M.K.M.).
Keywords
- GWAS
- functional variant
- positional cloning
- rat genetics
- substrain, QTL
ASJC Scopus subject areas
- Genetics