Bidanel, J.P.

Gilbert, H.J.

Groenen, M.A.M.

Heuven, H.C.M.

Riquet, J.

Tortereau, F.J.D.

English

Name not available

Comparison of two pig pedigrees regarding the effect of the IGF2 mutation on backfat.

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Comparison Of Two Pig Pedigrees Regarding The 
Effect Of The IGF2 Mutation On Backfat. 
F. Tortereau*†, H. Gilbert§, H.C.M. Heuven†‡, J.P. Bidanel§,                  
M.A.M. Groenen† and J. Riquet* 
 
 
Introduction 
Backfat thickness (BFT) is an economically important trait for which various QTL have been 
detected. Two analyses of similar Meishan x European F2 pedigrees carried out in France 
and in The Netherlands gave different results concerning the position and the imprinting 
status of a QTL detected in the telomeric part of SSC2. In 2000, de Koning et al. described a 
paternally expressed QTL at 36 cM on SSC2 whereas in 2002, Milan et al. described a QTL 
at 0 cM on SSC2, for which no imprinting effect was detected (Quintanilla et al., 2002). 
When the IGF2-intron3-G3072A mutation was described (Van Laere et al., 2003), Jungerius 
et al. (2004) showed that the paternally expressed QTL described by de Koning et al. was 
essentially explained by this mutation. On the contrary, Sanchez et al. (2006) showed that the 
IGF2-intron3-G3072A was not solely responsible for the growth and fatness QTL on SSC2. 
The aim of the present study was to combine these 2 pedigrees and understand the 
differences in QTL positions and imprinting status.  
Material and methods 
Animals and phenotypic data. For the French pedigree, 6 F1 were sires mated to 23 F1 
dams. Six large half-sib families (61 to 133 F2 pigs per sire) were obtained. BFT was 
measured on the carcasses of 521 male F2 pigs. For the Dutch pedigree, only the 24 largest 
half-sib families were considered. The 24 sires were mated to 181 F1 dams. On average, 
each F1 sire produced 36 F2 pigs. BFT was measured on the carcasses  of 565 F2 pigs. BFT 
was corrected for relevant fixed effects and covariates in each pedigreees prior to QTL 
detection. 
 
Genotyping and QTL detection.  Animals from both pedigrees were genotyped for a set of 
10 microsatellites markers. The IGF2 3072 G>A mutation was genotyped on the F1 animals; 
the genotypes of F2 at the IGF2 mutation were inferred, when possible, based on their 
genotypes at the surrounding markers. The two pedigrees were jointly analysed using 
interval mapping with the QTLMAP software (Le Roy et al., 1998). A substitution effect was 
estimated for each F1 sire at the maximum of the test statistics. The confidence interval QTL 
                                                 
*
 INRA Laboratoire de Génétique Cellulaire, 31320 Auzeville-Tolosane, France 
†
 Animal Breeding and Genetics Group, Wageningen University, 6700 AH Wageningen, The Netherlands 
‡
 Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands 
§
 INRA Génétique Animale et Biologie Intégrative, 78352 Jouy-en-Josas Cedex, France 
position was empirically determined by the “Lod drop-off” method (Lander and Kruglyak, 
1995). Additional QTL mapping analyses were performed after dividing the families into 2 
sub-groups based on the genotype of the F1 males at the IGF2 mutation (A/G or G/G). 
 
Analyses of variance. Analyses of variance were also carried out on F2 pigs to evaluate the 
effects of paternal and maternal IGF2 alleles on BFT. Different sub-groups of F2 pigs were 
also considered to check potential effects of maternal IGF2 alleles when heterozygous 
females were crossed with either homozygous and/or heterozygous males. 
 
Simulation studies.   
Simulation studies were done to check whether the observed differences concerning the 
imprinting status of the IGF2 gene could be due to the existence of a second QTL. First, the 
effect of the IGF2 mutation was estimated on the real dataset by setting the paternally 
inherited allele as a fixed effect in the QTL analysis of the combined pedigree. Then, 
assuming paternal expression of the IGF2 gene only, a QTL segregating at 44 cM was 
simulated in each pedigree. The q allele of the simulated QTL was fixed in the Meishan 
lines. Four frequencies of the Q allele of the simulated QTL were tested (100%, 75%, 50% 
and 25%, in the second grand-parental line) as well as 3 different effects (0.22, 0.32 or 0.42 
s.d. unit). Two thousand simulations were run for each pedigree x frequency x effect 
situation. Additionally, 2000 simulations were performed for the combined pedigree 
assuming a frequency of 50% of the Q allele in both grand-parental lines and an effect of 
0.32 s.d. unit. For each simulation, the effect of the maternal allele inherited at IGF2 on BFT 
was estimated with an analysis of variance. 
Results and discussion 
The QTL analysis of the combined pedigree gave a significant result for a QTL underlying 
BFT on SSC2, with a more likely position at 1 cM. The lod drop-off confidence interval 
spans from 0 to 47 cM, where previously published QTL had their most likely positions. 
 
0
0,2
0,4
0,6
0,8
1
1,2
1,4
0 20 40 60 80 100 120 140 160
SSC2 (cM)
LR
T 
/ 5
%
 
th
re
sh
o
ld
 
Figure 1: QTL mapping with the combined pedigree (black line), or with only G/G F1 
males (green line) or with only A/G males (blue line) for BFT on SSC2 (cM). The LRT 
is presented in proportion to the 5% threshold on the chromosome. 
The combined pedigree was then divided in 2 groups depending of the genotypes of the F1 
males at the IGF2 mutation. Fourteen F1 males were A/G (with 434 F2 progeny) and the 16 
remaining sires were G/G (with 652 F2 progeny). By analyzing these 2 groups, we 
demonstrated that the large significant region was in fact due to 2 different QTL.  
We confirmed that IGF2 is the first QTL segregating around 1 cM. The effect of the IGF2 
mutation was estimated at 0.48 s.d. unit in the combined pedigree. The second QTL was 
detected at 44 cM while analyzing the G/G F1 males families and is therefore not due to the 
effect of the IGF2 mutation (Figure 1). This second QTL had an effect of of 0.32 s.d. unit on 
BFT. Eleven of the 16 G/G F1 males were found to be heterozygous (Q/q).  
 
Analyses of variance were performed to evaluate the effect of the maternal allele inherited at 
the IGF2 mutation. Within the G/G F1 males group, a significant effect of the allele inherited 
from the dam at the IGF2 mutation was observed (p-value = 0.0134) in the sub-group of F2 
pigs having A/G F1 mothers. This significant effect is not in accordance with a paternal 
expression of the IGF2 gene.  
 
 Simulation studies were done to check whether the significant maternal effect at the IGF2 
locus could be due to the existence of the second QTL. A QTL was simulated at 44 cM and 
assuming an effect of the paternal allele inherited at the IGF2 gene of 0.48 s.d. unit. We 
observed highly different results between the French and Dutch pedigrees whatever the 
considered frequency and effect of the QTL allele (Table 1). A significant effect of the IGF2 
allele inherited from the mother was found in at least 32 % of the simulations run with the 
French pedigree whereas it was encountered in less than 10% of the simulations run with the 
Dutch pedigree. For the estimated frequency (75%) and effect (0.32 s.d. unit) of the second 
locus, a significant effect of the maternal IGF2 allele was observed in more than 50% of the 
simulations performed with the French pedigree, whereas it was observed in less than 4% of 
the simulations carried out with the Dutch pedigree. 
 
Frequency of the simulated Q allele 
 0.25 0.50 0.75 1.00 
36.95% 35.20% 33.35% 32.25% 
0.22 
6.45% 4.30% 3.75% 4.60% 
57.95% 56.15% 53.35% 51.70% 
0.32 
8.05% 4.55% 3.45% 5.4% 
75.20% 72.75% 70.45% 68.75% 
Ef
fec
t o
f th
e 
sim
u
la
te
d 
 
 
 
 
 
 
 
Q 
a
lle
le
 
0.42 
9.75% 4.90% 3.25% 5.70% 
 
Table 1: Percentages of simulations leading to the detection of a significant effect of the 
allele inherited from the mother at the IGF2 mutation on BFT in the French and Dutch 
pedigrees.  The effect was considered significant when p-value < 0.05.  
 
When analyzing the French pedigree it is therefore highly likely to detect a false effect of the 
IGF2 maternal allele. 
For the combined pedigree, the QTL was simulated with a Q allele frequency of 50% in each 
grand-parental line and an effect of 0.32 s.d. unit. A significant effect of the IGF2 allele 
transmitted by the F1 mothers appeared in 6.6% of the simulations. 
 
Conclusion 
These new analyses give some explanations for the conflicting results obtained from separate 
analyses of French and Dutch Meishan x European F2 pedigrees. The different QTL 
positions can be explained by the segregation of two genetically linked QTL, one of them 
being IGF2 gene. Concerning the imprinting status of the first QTL, a maternal effect of the 
IGF2 gene was hypothesized in the French pedigree where no imprinting effect was detected. 
Our simulation studies showed that the risk to detect a false significant effect of the maternal 
IGF2 allele in this pedigree is too high to support this hypothesis. Therefore, the statistical 
significant effect we observed is probably due to genetic linkage existing between the IGF2 
gene and the second detected QTL. Finally, it is interesting to notice that the risk to detect a 
false significant effect of the maternal IGF2 allele is higher in the French pedigree than in the 
Dutch pedigree. This difference can be explained by the 2 pedigrees’ structures: many little 
half-sib families versus a few large half-sib families. 
References 
De Koning et al. (2000). Proc. Natl. Acad. Sci., 97:7947-7950  
Jungerius et al. (2004). Genet. Res., Camb., 84:95–101 
Lander and Kruglyak (1995). Nat. Genet., 11:241-247 
Le Roy et al. (1998). In Proc 6th WCGALP, volume 26, pages 257–260. 
Milan et al. (2002). Genet. Sel. Evol., 34:705–728 
Quintanilla et al. (2002). Genet. Sel. Evol., 34:193–210 
Sanchez et al. (2006). In Proc 8th WCGALP, communication 13-08 
Van Laere et al. (2003). Nature, 425:832-836 
 


Comparison of two pig pedigrees regarding the effect of the IGF2 mutation on backfat.

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