Igly4^PWK/PhJ
QTL Variant Detail

Summary

• QTL variant: Igly4^PWK/PhJ
• Name: IgG glycosylation 4, GP17a; PWK/PhJ
• MGI ID: MGI:6382454
• QTL: Igly4 Location: Chr12:114429496-118423781 bp Genetic Position: Chr12, Syntenic

Variant origin

• Strain of Specimen: PWK/PhJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:276361

QTL Reference Notes

The Collaborative Cross (CC) is a large (~1,000 line) panel of recombinant inbred (RI) mouse strains being developed through a community effort (Churchill et al. 2004). The CC combines the genomes of eight genetically diverse founder strains - A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ - to capture nearly 90% of the known variation present in laboratory mice. CC strains are derived using a unique funnel breeding scheme. Once inbred, the RI CC lines can be used to generate thousands of potential 'outbred' but completely reproducible genomes through the generation of recombinant inbred crosses (RIX). The designation 'PreCC' is used to describe a mapping population of CC mice that is still at incipient stages of inbreeding. CTC (2004), Churchill, G. A., et al.. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet. 36, 1133-7.

Antibodies are both important mediators of immunity and widely used drugs. Antibodies of the Immunoglobulin G (IgG) isotypes are most prevalent in circulation. IgG glycosylation is essential for function of the immune system, but the genetic and environmental factors that underlie its inter-individual variability are not well defined. The authors analyzed the IgG glycome composition of 95 CC#/Geni Collaborative Cross (CC) strains.

CC#/Geni strains were genotyped at NeogenGeneSeek (Lincoln, NE) using the MegaMUGA platform. Of the 77,808 genotyped SNPs, 68,903 were reliably homozygous among the eight founders, with at least one founder having the non-reference allele. These SNPs were extracted and applied for founder haplotype estimation using a web-based Collaborative Cross haplotype estimation tool. QTL mapping was performed using an online tool (http://www.sysgen.org/GeneMiner/) that interfaces the inferred haplotypes of CC strains and a mixed model, implemented in the R package QTLRel.

Ten genetic loci associated with variation in levels of IgG glycosylation were identified:

Igly1 (IgG glycosylation 1, GP1) maps to Chr 12: 114465876 - 117866912 with a peak LOD score of 19 at 112 Mb. CAST/EiJ and PWK/PhJ contribute the high allele at Igly1.

Igly2 (IgG glycosylation 2, GP14) maps to Chr 12: 111770863 - 121233193 with a peak LOD score of 10.5 at 118 Mb. CAST/EiJ and PWK/PhJ contribue the low allele and C57BL/6J and NOD/ShiLtJ contribute the high allele at Igly2.

Igly3 (IgG glycosylation 3, GP16) maps to Chr 12: 114465876 - 117866912 with a peak LOD score of 16 at 112 Mb. A/J, NZO/HlLtJ, and WSB/EiJ contribute the low allele at Igly3.

Igly4 (IgG glycosylation 4, GP17a) maps to Chr 12: 114465876 - 118460046 with a peak LOD score of 8.5 at 112 Mb. CAST/EiJ and PWK/PhJ contribute the low allele at Igly4.

Igly5 (IgG glycosylation 5, GP20) maps to Chr 12: 113409985 - 117866912 with a peak LOD score of 17.5 at 118 Mb. CAST/EiJ and PWK/PhJ contribute the low allele and C57BL/6J and NOD/ShiLtJ contribute the high allele at Igly5.

Igly6 (IgG glycosylation 6, GP6) maps to Chr 15: 74228691 - 82789955 with a peak LOD score of 8.5 at 80 Mb. CAST/EiJ and PWK/PhJ contribute the high allele at Igly6.

Igly7 (IgG glycosylation 7, GP10) maps to Chr 15: 77910719 - 82789955 with a peak LOD score of 8.5 at 80 Mb. CAST/EiJ and PWK/PhJ contribute the high allele at Igly7.

Igly8 (IgG glycosylation 8, GP17b) maps to Chr 10: 93025664 - 94091756 with a peak LOD score of 9 at 92.5 Mb. CAST/EiJ and PWK/PhJ contribute the high allele and NOD/ShiLtJ contributes the low allele at Igly8.

Igly9 (IgG glycosylation 9, GP17b) maps to Chr 16: 14957359 - 20284763 with a peak LOD score of 9 at 18 Mb. C57BL/6J and NZO/HlLtJ contribute the high allele and NOD/ShiLtJ and WSB/EiJ contribute the low allele at Igly9.

Igly10 (IgG glycosylation 10, GP25) maps to Chr 7: 149610152 - 151380812 with a peak LOD score of 8.75 at 150 Mb. A/J contributes the high allele and WSB/EiJ contributes the low allele at Igly10.

Two suggestive QTL were also identified: one on Chr 4 and one on Chr 2.

All LOD scores were inferred from Figures 5, S7, and S8.

All genome coorinates are relative to NCBI Build 37 (mm9).

References

• Original: J:276361 Kristic J, et al., Profiling and genetic control of the murine immunoglobulin G glycome. Nat Chem Biol. 2018 May;14(5):516-524
• All: 1 reference(s)