Experiment
Genomic imprinting refers to the pattern of monoallelic parent-of-origin-dependent gene expression where one of the two alleles at a locus is expressed and the other silenced. The authors searched for QTL exhibiting imprinting effects on mandible size and shape traits in a large F3 population of mice originating from an intercross of LG/J and SM/J inbred strains. Crossing of the (LG/J x SM/J)F1 hybrids produced 510 F2 mice that in turn were crossed to yield 200 F3 families containing a total of 1632 mice.
Both left and right sides of the mandibles in each mouse were separated at the mandibular symphysis, placed under a microscope, and their images were scanned into a computer. The authors then recorded x and y coordinates for 15 landmarks located around the outline of the mandible. A total of 1889 mice were available for analysis, 374 from the F2 generation and 1515 from the F3 generation.
A total of 353 SNP markers were scored for all available F2 and F3 mice by the Illumina Golden-Gate assay. These markers effectively covered all 19 autosomes, with an average interval of 45 cM between markers except for several regions in the genome where there was little polymorphism between the LG/J and SM/J strains. Haplotype reconstruction was accomplished with the PedPhase program that allowed the authors to distinguish each of the four genotypes at each SNP locus in all F3 mice.
The authors searched for QTL for mandible centroid size and shape in the F3 mice using the regression approach of Haley and Knott (1992) implemented with the canonical correlation (CANCORR) procedure in SAS (SAS Institute, 1992). If evidence for a QTL for mandible size or shape was found on a given chromosome, the authors tested for the presence of two QTL on that chromosome.
The authors discovered a total of 51 QTL affecting mandible size and shape:
(The significance test is given as the negative log of the probability [LPR])
(All coordinates relative to NCBI37/mm9)
Mancz1 (mandible centroid size 1), significant at the chromosome level, maps to Chr 1 with a peak LPR score of 7.45 at rs13475927 (34.70 cM; 75.21 Mb).
Mancz1 accounts for 2.47% of the total trait variance and exerts additive effects.
Mancz2 (mandible centroid size 2), significant at the genome-wide level, maps to Chr 2 with a peak LPR score of 10.15 at rs13476473 (27.38 cM; 46.00 Mb).
Mancz2 accounts for 3.31% of the total trait variance and exerts additive and imprinting effects.
Mancz3 (mandible centroid size 3), significant at the chromosome level, maps to Chr 2 with a peak LPR score of 6.92 at rs3689258 (84.82 cM; 169.00 Mb).
Mancz3 accounts for 2.32% of the total trait variance and exerts additive effects.
Mancz4 (mandible centroid size 4), significant at the chromosome level, maps to Chr 3 with a peak LPR score of 7.54 at rs3684333 (54.17 cM; 107.27 Mb).
Mancz4 accounts for 2.44% of the total trait variance and exerts additive and imprinting effects.
Mancz5 (mandible centroid size 5), significant at the genome-wide level, maps to Chr 4 with a peak LPR score of 11.41 at gnf04.062.327 (29.93 cM; 65.81 Mb).
Mancz5 accounts for 3.55% of the total trait variance and exerts additive effects.
Mancz6 (mandible centroid size 6), significant at the genome-wide level, maps to Chr 6 with a peak LPR score of 17.18 at rs6265387 (74.87 cM; 148.18 Mb).
Mancz6 accounts for 5.64% of the total trait variance and exerts additive and imprinting effects.
Mancz7 (mandible centroid size 7), significant at the genome-wide level, maps to Chr 8 with a peak LPR score of 10.03 at rs13479811 (37.16 cM; 66.16 Mb).
Mancz7 accounts for 3.24% of the total trait variance and exerts additive effects.
Mancz8 (mandible centroid size 8), significant at the genome-wide level, maps to Chr 10 with a peak LPR score of 17.29 at rs3704401 (43.79 cM; 99.22 Mb).
Mancz8 accounts for 5.34% of the total trait variance and exerts additive effects.
Mancz9 (mandible centroid size 9), significant at the chromosome level, maps to Chr 11 with a peak LPR score of 8.56 at rs6180460 (61.62 cM; 102.78 Mb).
Mancz9 accounts for 2.70% of the total trait variance and exerts additive effects.
Mancz10 (mandible centroid size 10), significant at the genome-wide level, maps to Chr 12 with a peak LPR score of 11.80 at rs3709102 (20.20 cM; 43.57 Mb).
Mancz10 accounts for 3.77% of the total trait variance and exerts imprinting effects.
Mancz11 (mandible centroid size 11), significant at the chromosome level, maps to Chr 13 with a peak LPR score of 8.91 at rs6296621 (37.98 cM; 83.07 Mb).
Mancz11 accounts for 2.87% of the total trait variance and exerts additive effects.
Mancz12 (mandible centroid size 12), significant at the genome-wide level, maps to Chr 14 with a peak LPR score of 15.95 at rs3663148 (37.75 cM; 81.25 Mb).
Mancz12 accounts for 4.92% of the total trait variance and exerts additive and dominance effects.
Mancz13 (mandible centroid size 13), significant at the genome-wide level, maps to Chr 15 with a peak LPR score of 12.36 at rs3720931 (44.21 cM; 89.55 Mb).
Mancz13 accounts for 3.90% of the total trait variance and exerts additive effects.
Mancz14 (mandible centroid size 14), significant at the chromosome level, maps to Chr 17 with a peak LPR score of 9.36 at rs6358703 (12.21 cM; 26.58 Mb).
Mancz14 accounts for 3.07% of the total trait variance and exerts additive effects.
Manh49 (mandible shape 49), significant at the genome-wide level, maps to Chr 1 with a peak LPR score of 46.75 at rs13475927 (34.70 cM; 75.21 Mb).
Manh49 exerts additive effects.
Manh50 (mandible shape 50), significant at the genome-wide level, maps to Chr 1 with a peak LPR score of 33.38 at rs3688042 (55.89 cM; 151.11 Mb).
Manh50 exerts additive effects.
Manh51 (mandible shape 51), significant at the genome-wide level, maps to Chr 2 with a peak LPR score of 42.51 at rs13476473 (27.38 cM; 46.00 Mb).
Manh51 exerts additive effects.
Manh52 (mandible shape 52), significant at the genome-wide level, maps to Chr 2 with a peak LPR score of 30.84 at gnf02.161.674 (76.23 cM; 158.20 Mb).
Manh52 exerts additive effects.
Manh53 (mandible shape 53), significant at the chromosome level, maps to Chr 3 with a peak LPR score of 10.18 at rs6335414 (25.05 cM; 52.65 Mb).
Manh53 exerts additive effects.
Manh54 (mandible shape 54), significant at the genome-wide level, maps to Chr 3 with a peak LPR score of 27.99 at rs3671622 (52.93 cM; 101.81 Mb).
Manh54 exerts additive effects.
Manh55 (mandible shape 55), significant at the genome-wide level, maps to Chr 4 with a peak LPR score of 40.69 at gnf04.062.327 (29.93 cM; 65.81 Mb).
Manh55 exerts additive effects.
Manh56 (mandible shape 56), significant at the genome-wide level, maps to Chr 4 with a peak LPR score of 31.59 at rs13477996 (61.67 cM).
Manh56 exerts additive effects.
Manh57 (mandible shape 57), significant at the genome-wide level, maps to Chr 5 with a peak LPR score of 17.01 at rs3711950 (33.89 cM; 62.81 Mb).
Manh57 exerts additive effects.
Manh58 (mandible shape 58), significant at the genome-wide level, maps to Chr 5 with a peak LPR score of 21.19 at rs13478487 (56.93 cM; 118.44 Mb).
Manh58 exerts additive effects.
Manh59 (mandible shape 59), significant at the chromosome level for females only, maps to Chr 6 with a peak LPR score of 10.96 at rs13478602 (0.00 cM; 3.80 Mb).
Manh59 exerts additive effects.
Manh60 (mandible shape 60), significant at the chromosome level for males only, maps to Chr 6 with a peak LPR score of 14.31 at rs13478762 (25.79 cM; 54.37 Mb).
Manh60 exerts additive effects.
Manh61 (mandible shape 61), significant at the genome-wide level, maps to Chr 6 with a peak LPR score of 62.36 at rs6265387 (74.87 cM; 148.18 Mb).
Manh61 exerts additive effects.
Manh62 (mandible shape 62), significant at the genome-wide level, maps to Chr 7 with a peak LPR score of 51.71 at rs3683030 (39.86 cM; 87.13 Mb).
Manh62 exerts additive, dominance, and imprinting effects.
Manh63 (mandible shape 63), significant at the genome-wide level, maps to Chr 7 with a peak LPR score of 22.87 at rs6216320 (76.45 cM; 139.60 Mb).
Manh63 exerts additive effects.
Manh64 (mandible shape 64), significant at the genome-wide level, maps to Chr 8 with a peak LPR score of 42.21 at rs13479811 (37.16 cM; 66.62 Mb).
Manh64 exerts additive and dominance effects.
Manh65 (mandible shape 65), significant at the genome-wide level, maps to Chr 8 with a peak LPR score of 42.93 at rs13480023 (77.87 cM; 122.14 Mb).
Manh65 exerts additive effects.
Manh66 (mandible shape 66), significant at the genome-wide level, maps to Chr 9 with a peak LPR score of 37.13 at rs3670579 (37.77 cM; 67.03 Mb).
Manh66 exerts additive effects.
Manh67 (mandible shape 67), significant at the genome-wide level, maps to Chr 9 with a peak LPR score of 26.50 at rs3723953 (58.94 cM; 111.08 Mb).
Manh67 exerts additive effects.
Manh68 (mandible shape 68), significant at the genome-wide level, maps to Chr 10 with a peak LPR score of 40.53 at rs13480638 (28.47 cM; 69.50 Mb).
Manh68 exerts additive and dominance effects.
Manh69 (mandible shape 69), significant at the genome-wide level, maps to Chr 10 with a peak LPR score of 38.89 at rs13480797 (61.08 cM; 121.58 Mb).
Manh69 exerts additive and dominance effects.
Manh70 (mandible shape 70), significant at the genome-wide level, maps to Chr 11 with a peak LPR score of 39.44 at rs3690160 (21.95 cM; 36.81 Mb).
Manh70 exerts additive and imprinting effects.
Manh71 (mandible shape 71), significant at the genome-wide level, maps to Chr 11 with a peak LPR score of 65.10 at rs3710148 (55.77 cM; 96.35 Mb).
Manh71 exerts additive effects.
Manh72 (mandible shape 72), significant at the genome-wide level, maps to Chr 12 with a peak LPR score of 44.05 at rs13481361 (6.82 cM; 24.12 Mb).
Manh72 exerts additive effects.
Manh73 (mandible shape 73), significant at the genome-wide level, maps to Chr 12 with a peak LPR score of 35.03 at rs6263380 (36.86 cM; 79.67 Mb).
Manh73 exerts additive effects.
Manh74 (mandible shape 74), significant at the genome-wide level, maps to Chr 13 with a peak LPR score of 26.87 at rs3718727 (28.46 cM; 65.35 Mb).
Manh74 exerts additive effects.
Manh75 (mandible shape 75), significant at the genome-wide level, maps to Chr 13 with a peak LPR score of 23.85 at rs13482028 (57.91 cM; 112.67 Mb).
Manh75 exerts additive effects.
Manh76 (mandible shape 76), significant at the chromosome level, maps to Chr 14 with a peak LPR score of 12.22 at rs13482143 (15.90 cM; 37.70 Mb).
Manh76 exerts additive effects.
Manh77 (mandible shape 77), significant at the genome-wide level, maps to Chr 14 with a peak LPR score of 17.46 at rs3718262 (39.17 cM; 88.00 Mb).
Manh77 exerts additive effects.
Manh78 (mandible shape 78), significant at the genome-wide level, maps to Chr 15 with a peak LPR score of 26.76 at rs3695416 (15.83 cM; 38.49 Mb).
Manh78 exerts additive and dominance effects.
Manh79 (mandible shape 79), significant at the genome-wide level, maps to Chr 15 with a peak LPR score of 35.32 at rs13482726 (54.47 cM; 96.02 Mb).
Manh79 exerts additive effects.
Manh80 (mandible shape 80), significant at the genome-wide level, maps to Chr 16 with a peak LPR score of 37.92 at rs6188665 (34.62 cM; 64.43 Mb).
Manh80 exerts additive effects.
Manh81 (mandible shape 81), significant at the genome-wide level, maps to Chr 17 with a peak LPR score of 39.44 at CEL-7_40073719 (16.37 cM; 39.44 Mb).
Manh81 exerts additive effects.
Manh82 (mandible shape 82), significant at the chromosome level, maps to Chr 17 with a peak LPR score of 13.99 at rs3684732 (53.21 cM; 80.84 Mb).
Manh82 exerts additive effects.
Manh83 (mandible shape 83), significant at the genome-wide level, maps to Chr 18 with a peak LPR score of 19.43 at rs13483200 (1.84 cM; 9.95 Mb).
Manh83 exerts additive effects.
Manh84 (mandible shape 84), significant at the genome-wide level, maps to Chr 18 with a peak LPR score of 19.66 at gnf18.069.928 (40.09 cM; 71.88 Mb).
Manh84 exerts additive effects.
Manh85 (mandible shape 85), significant at the genome-wide level, maps to Chr 19 with a peak LPR score of 18.41 at rs3714482 (26.97 cM; 28.19 Mb).
Manh85 exerts additive effects.
Six QTL exhibited differences between reciprocal heterozygotes, the usual signature of imprinting effects. However, the authors' analysis showed that only one of these QTL (Mancz10) exhibited a pattern consistent with true imprinting effects, whereas reciprocal heterozygote differences in the other five all were due to maternal genetic effects. The authors concluded that genomic imprinting has a negligible effect on these specific morphometric traits, and that maternal genetic effects may account for many of the previously reported instances of apparent genomic imprinting.
The data suggest that the LG/J alleles tend to increase mandible size.
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