The X Chromosome harbors quantitative trait loci for backfat thickness and intramuscular fat content in pigs Barbara Harlizius, Annemieke P. Rattink, Dirk J. de Koning, Marilyne Faivre, Ruth G. Joosten, Johan A.M. van Arendonk, Martien A.M. Groenen Department of Animal Sciences, Animal Breeding and Genetics Group, Wageningen Institute of Animal Sciences, Wageningen University, PO Box 338, 6700 AH Wageningen, The Netherlands Recieved: 6 December 1999 / Accepted: 14 April 2000 Genetic markers have been used in experimental crosses in pigs to dissect genetic variation in quantitative traits (e.g., Andersson et al. 1994; Knott et al. 1998; Rohrer and Keele 1998). We reported recently on the search for autosomal quantitative trait loci (QTL) for fatness traits in an experimental intercross between the obese Chinese Meishan breed and lean Dutch White production lines (De Koning et al. 1999; Rattink et al. 2000). In this paper, the analysis to look for QTL on the X Chromosome (Chr) in this cross is presented. Briefly, 19 Meishan boars were mated to 120 sows of White lines from five Dutch breeding companies. From the F 1 animals, 39 F 1 boars and 124 F 1 sows were randomly selected to generate the F 2 generation. The F 2 animals (n  1293), their F 1 parents, and the Meishan grandfathers were genotyped for five microsatellite markers located in the non-pseudoautosomal region of the X Chr. The percentage of fat within the muscle (intramuscular fat, IMF) and backfat thickness (BFT) of the Musculus longissimus was recorded on 785 F 2 animals after slaughter at a live weight of approximately 90 kg (for details see Janss et al. 1997). For QTL analysis, interval mapping by regression was carried out following a line cross analysis as described previously (De Koning et al. 1999) where the founder lines were assumed to be fixed for dif- ferent QTL alleles. The model was extended to account for dif- ferences between sexes at the X Chr. The contrast between the Meishan and the White allele for the estimation of the QTL effect was calculated within male and female F 2 offspring separately because of the design of the cross. Male F 2 offspring carry only a maternal copy of the X Chr originating from the Meishan or from the White grandparents, whereas all female offspring inherited in addition the paternal copy of the X Chr from the White lines. Furthermore, the model was accommodated to take into account that the X Chr cannot recombine in male F 1 parents. The female genetic map calculated from our data (Fig. 1) shows the same marker order but differences in distances between markers compared with the map of Rohrer et al. (1996). An in- crease in length of roughly 10 cM (Kosambi) is observed between markers SW2534 and SW2456 (37.8 cM versus 27.6 cM) as well as between SW2476 and SW1943 (21.5 cM versus 9.8 cM). However, a smaller distance is observed on our map in the interval between SW2456 and SW2476 (9.4 cM versus 19.8 cM). Genotypes were evaluated independently by two different persons, and sensitivity analysis did not point towards specific families causing these dif- ferences (data not shown). The number of informative meioses in this study ranges from 1551 (SW2476) to 1854 (SW2534). As the mapping population of Rohrer et al. (1996) consisted of 94 F 2 animals and only female parents contribute mapping information, their estimates of recombination frequencies are expected to be inaccurate. This is the likely explanation for the observed differ- ences. Figure 1 shows the test statistics of the QTL analysis for IMF and BFT and the threshold levels along the genetic map of the X Chr. For both fatness traits, a genomewide significant (p < 5%) QTL is detected. The estimated position of the QTL is different between the two traits, but they are in adjacent marker intervals at 60 cM for BFT and 69 cM for IMF (Table 1). From these data we cannot conclude whether there are two separate loci or the same QTL affects both traits. As expected, the alleles from the obese Meishan breed increase the percentage of intramuscular fat as well as backfat thickness. The estimated size of the QTL effects is smaller in females (1.02 mm BFT, 0.13% IMF) than in males (1.47 mm BFT, 0.21% IMF) for both traits (Table 1). This might be caused by random inactivation of the X Chr in females. For every chromosomal interval, the effect in females is estimated as the contrast between animals that inherited two X Chr intervals de- rived from the White lines and those that are expected to be het- erozygous for the interval, with one copy from Meishan and an- other copy from the White lines. Random X inactivation is known to occur quite early in development, and therefore larger parts of a tissue might originate from the same precursor cell and have the same X chromosomal inactivation imprint (Migeon 1994). There- fore, some females are expected to have inactivated the Meishan- derived X Chr in the relevant tissues and express the White- derived X Chr. On the other hand, these differences in effects between the sexes could reflect any other biological mechanism of sexually dimorphic gene expression, which can also be caused by interaction with autosomal genes (e.g., Davey et al. 1999). The observed effect on BFT is comparable in size to the effect of the halothane mutation at the porcine ryanodine receptor gene (Fujii et al. 1991) in a Wild boar x Large White cross (Knott et al. 1998). They estimated that the mutation, which is not present in our families, reduces back fat by 1.63 mm in heterozygous males. A QTL affecting backfat thickness in pigs at a similar location on the X Chr has been reported by Rohrer and Keele (1998). In a Meishan x White composite backcross, a significant QTL is de- tected for different back fat measurements. The additive effects reported across sexes range from 0.292 to 0.419 cm increase of BFT for the Meishan allele, depending on the area of the carcass where back fat is measured. These estimates are much larger than in our study. This might be partly owing to a higher slaughter weight (100 kg) in the study of Rohrer and Keele (1998) because back fat accumulates exponentially with age. Furthermore, in the current study male animals were boars, whereas Rohrer and Keele (1998) investigated castrates. It is known that castrates accumulate more fat, and consequently QTL effects might be more pro- nounced. Also, the locations sampled along the spine differ be- Correspondence to: B. Harlizius; E-mail: Barbara.Harlizius@alg. vf.wau.nl. Mammalian Genome 11, 800–802 (2000). DOI: 10.1007/s003350010147 © Springer-Verlag New York Inc. 2000 Incorporating Mouse Genome