Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'.
Document Type
Article
Publication Date
2005
Keywords
Genome-Human, Hematopoietic-Stem-Cells, Humans, Molecular-Sequence-Data, Quantitative-Trait-Loci, RNA-Messenger
First Page
225
Last Page
232
JAX Source
Nat Genet 2005 Mar; 37(3):225-32.
Abstract
We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.
Recommended Citation
Bystrykh L,
Weersing E,
Dontje B,
Sutton S,
Su AI,
Vellenga E,
Wang J,
Manly KF,
Lu L,
Chesler EJ,
et a.
Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'. Nat Genet 2005 Mar; 37(3):225-32.