Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  X
• Reference
  J:87114 Dorward AM, et al., High-resolution genetic map of X-linked juvenile-type granulosa cell tumor susceptibility genes in mouse. Cancer Res. 2003 Dec 1;63(23):8197-202
• ID
  MGI:3574517

Genes

Gene	Assay Type
Gct4	resistance/susceptibility
DXMit45	PCR
DXMit170	PCR
Ar	reported elsewhere
Gct6	resistance/susceptibility
DXMit79	PCR
DXMit4	PCR

Notes

• Experiment
  The position of Gct4 was refined to a 3 cM interval on mouse Chromosome X between DXMit45 (30.7 cM) and DXMit170 (41.5 cM) using congenic mouse lines.
  
  Three congenic lines carrying different length segments of SJL-derived donor DNA between DXMit96 (37 cM) and DXMit158 (43.6 cM) were constructed on an SWR genetic background. Background strain SWR is susceptible to spontaneous development of ovarian granulosa cell tumors and this susceptibility is enhanced when combined with SJL genetic material. The SJL-derived allele at Gct4 exhibits a parent-of-origin effect. Female animals inheriting the paternal Gct4^SJL allele are susceptible to granulosa cell tumor compared to when the allele is inherited maternally.
  
  A congenic line carrying CAST/Ei-derived donor DNA between DXMit46 (24.5 cM) and DXMit234 (58 cM) on an SWR genetic background was also constructed. This congenic line is resistant to granulosa cell tumor development, which would indicate that the CAST/Ei-derived allele confers a protective effect.
  
  Ar maps within the 3 cM Gct4 interval and is considered an attractive candidate gene. Sequence analysis of the Ar coding region did not reveal any differences between SWR and SJL. However, when the SWR/SJL sequence is compared to the CAST/Ei sequence 5 nucleotide substitutions are found in the coding region. Three of the changes result in a missense mutation and 2 of the changes are silent mutations.
  
  When the SWR.CAST congenic was crossed with SWR.SJL congenics the existence of a new modifier was revealed. This modifier is named Gct6 and maps 6.5 cM distal to Gct4. Gct6 is located in a 1 cM interval between DXMit79 (50.5 cM) and DXMit4 (58 cM). SJL-derived alleles at Gct6 support the tumor susceptibility effect of Gct4^SJL.