Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  11
• Reference
  J:306895 Brown A, et al., The lifespan quantitative trait locus gene Securin controls hematopoietic progenitor cell function. Haematologica. 2020;105(2):317-324
• ID
  MGI:7314895

Genes

Gene	Assay Type
Rhdrox1	visible phenotype
Rhdrox2	visible phenotype

Notes

• Experiment
  The percentage of murine hematopoietic stem and progenitor cells, which present with a loss of function upon treatment with the genotoxic agent hydroxyurea (HU), is inversely correlated to the mean lifespan of inbred mice, including the long-lived C57BL/6J and short-lived DBA/2J strains.
  
  Linkage analysis and determination of the likelihood ratio statistic values for suggestive linkage were performed as described using WebQTL.
  
  Quantitative trait locus (QTL) mapping in BXD recombinant inbred strains identified a region spanning 12.5 cM on the proximal part of chromosome 11 linked to both the percentage of dysfunctional hematopoietic stem and progenitor cells as well as regulation of lifespan (genome coordinates relative to GRCm38/mm10):
  
  Rhdrox1 (response to hydroxyurea 1, hematopoietic stem and progenitor cell differential response) maps to Chr 11: 35 - 75 Mb.
  
  Rhdrox2 (response to hydroxyurea 2, mean life span) maps to Chr 11: 35 - 75 Mb.
  
  Rhdrox1 and Rhdrox2 both map to the same location. By generating and analyzing reciprocal congenic mice for this locus, the authors demonstrate that this region indeed determines the sensitivity of hematopoietic stem and progenitor cells to HU.
  
  A DBA/2J allele at the genetic microsatellite marker D11Mit174 (Chr 11: 42,593,949 - 42,594,095, which is within the area with the highest level of linkage) correlated in the BXD RI set, as anticipated, with higher HU-susceptibility rates of hematopoietic stem and progenitor cells (HSPC) and a lower mean life span.
  
  The authors verified pituitary tumor-transforming gene 1 (Pttg1; MGI:1353578) as the quantitative trait gene regulating the differential response of hematopoietic stem and progenitor cells to hydroxyurea treatment and which might therefore be linked to the regulation of lifespan.