Experiment
Susceptibility to Leishmania major infection was analyzed in Recombinant Congenic line CcS/Dem. CcS/Dem RC lines are derived from BALB/cHeA (Leishmania susceptibility) and STS/A (Leishmania resistant). BALB/cHeA exhibits a high IgE serum level after L. major infection, where the STS/A resistant strain has a low level.
CcS/Dem lines carry a random set of 12.5% of genes from the resistant STS/A strain and 87.5% genes from the susceptible BALB/c strain. Two CcS/Dem strains, CcS16 (a high IgE producer) and CcS20 (a low IgE producer) were analyzed for genes that control these levels after Leishmania major infection.
In the cross of 498 (BALB/c x CsS20)F2 mice a QTL was detected linked with IgE production on mouse Chromosome 5 spanning markers D5Mit55, D5Mit114 and D5Mit175 and peaking with D5Mit55 at 28 cM, p<0.00000243.
03.10.2016 Curator Note: Table 3 pairs this Chromosome 5 QTL with a previously detected QTL, Lmr3, which also influenced IgE production post infection (J: 82715). However because Lmr3 was originally identified using a (BALB/c x CcS5)F2 mapping population, which differs from the mapping population used here, we consider this study a separate experiment and have named the QTL, Lmr24. Lmr24 represents the broader QTL composed of individual traits identified in response to infection. We have created Lmr24a to represent the QTL that influences IgE production post infection. The STS/A allele at Lmr24a is associated with lower levels of IgE production after infection.
Linkage analysis also revealed four additonal QTL influencing IgE production in the (BALB/c x CsS20)F2 mapping population:
Lmr8 on Chr 1, was mapped with markers D1Mit14 p<0.0000557, D1Mit227 p<0.00157 and D1Mit17 p<0.0209. BALB/c alleles at this locus are associated with higher levels of IgE. [Table 2.]
0.3.22.2016 Curator Note: We have created QTL Lmr8a to represent the QTL identified here mapping with marker D1Mit14 and identified in interaction with Lmr11a (D3Mit11) and Lmr11b (D3Mit25). [Table 2]. Lower IgE levels were observed in interaction of BALB/c homozygotes at Lmr11a, Lmr11b and STS/A homozygotes at Lmr8a.
Lmr9 on Chr 4 mapped with D4Mit149 p<0.00313);
Lmr10 on Chr 8 mapped with D8Mit125 and D8Mit54 (p< 0.000731 and 0.0000111 respectively.
03.17.2016 Curator Note: We have created QTL Lmr10a to represent the QTL mapping with D8Mit125 and D8Mit54 and influencing IgE production.
Scvr and Casp3 are potential candidate genes for Lmr10a [Table 3].
BALB/c alleles at Lmr8, Lmr9 and Lmr10 are asociated with high IgE levels post infection.
Lmr11 on Chr 3 mapping with D3Mit11 and D3Mit25 was identified influencing IgE levels in interaction with Lmr8a (D1Mit14), at Lmrlla (D3Mit11) p<0.0229 and at Lmr11b (D3Mit25) p<0.000522, respectively. BALB/c alleles at Lmr8a (D1Mit14) and at both Lmr11a and Lmrllb interact in determining IgE levels, lower levels observed in interaction of BALB/c homozygotes at Lmr11a, Lmr11b and STS/A homozygotes at Lmr8a.
Il12a and Il6ra are potential candiadte genes for Lmr11 [Table 3].
Analysis Tools