International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


A QTL UNDERLYING HEMATOPOIETIC STEM CELL PROLIFERATION COLOCALIZES WITH A CLUSTER OF DIFFERENTIALLY EXPRESSED GENES AND REGIONS OF INCREASED MEIOTIC RECOMBINATION

Leonid Bystrykh
State University of Groningen
Ant.Deusinglaan 1
Groningen 9713 AV The Netherlands

Co-Authors: 1) Bystrykh L, 1)Weersing E, 2)Geiger H, 3)Ivanova N, 2)Van Zant G, 3)Lemischka I, 1)Vellenga E, 1)de Haan G
Institutions: 1)State University of Groningen, 2)University of Kentucky, 3)Princeton University

We have previously shown that hematopoietic stem cells from DBA/2 and C57BL/6 mice differ in their cell cycle activity We have mapped a major quantitative trait locus (QTL) associated with variation in cell proliferation to chromosome 11. In order to detect candidate genes causing these differences we performed subtractive hybridizations and gene array assays using cDNA from highly purified stem cells from both strains. The results revealed an unexpectedly high frequency of differently expressed genes (ESTs) mapping to chromosome 11. Intriguingly, detailed mapping of those transcripts showed that they occured in three distinct clusters. The largest cluster colocalizes exactly with the stem cell cycling QTL. Using newly derived backcross panels and the BXD recombinant inbred database, we found the three clusters of differentially expressed transcripts to coincide with regions of increased frequency of meiotic recombination. In addition, sequence analysis of selected genes in those clusters demonstrated profound sequence variations. Taking into account the high functional heterogeneity of the clustered genes we postulate that the QTL underlying variation in stem cell proliferation may not be due to a single gene but rather may involve a genomic disparity affecting a higher order of chromosomal organization. These differences lead to increased rates of meiotic recombination and aberrant expression of a large cohort of clustered genes. It is tempting to speculate that many QTLs may result from anomalous expression of a collection of highly linked genes. In addition, a similar model may apply for tumorigenic chromosomal translocations.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012