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Genome Res. 16:1191-1192, 2006 ©2006 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/06 $5.00 Forum Mouse SNPs for evolutionary biology: Beware of ascertainment biasesLaboratoire Génome, Populations, Interactions, Adaptation (UMR5171), Université Montpellier II, 34095 Montpellier Cedex 5, France
Recently, Harr (2006)
Using SNP data in population genetics and evolution, especially for quantifying differentiation or divergence, requires a careful and unbiased choice of SNPs. Ascertainment biases in the SNP discovery and choice processes can have various origins and can sometimes lead to erroneous conclusions (Morin et al. 2004
Most of the SNPs in the data set that Harr used were chosen by comparing the full sequences of five strains, from Celera (strains C57/BL/6J, DBA/2J, A/J, 129S1/SvImJ, and 129X1/SvJ) (Pletcher et al. 2004 We sliced the genome in fragments of 100 kb, and for each fragment we calculated the resemblance (proportion of identical SNPs) of each of the six SNP discovery strains to PWD/PhJ, from which we subtracted the greater of its resemblances to WSB/EiJ and CAST/EiJ. Positive values of the resulting index thus indicate a musculus origin; negative values, a non-musculus origin. Figure 1 (thin curves) presents the results for the chromosomes on which Harr found significant differentiation peaks. Note that in some regions (such as the distal chromosome 1 and three segments of chromosome 14), the index of the SNP discovery strains oscillates around zero, which prevents classification. This is because in these regions the reference musculus strain (PWD/EiJ) is of domesticus origin (analysis not shown, but a plausible result since the strain comes from the Czech Republic, close to the natural hybrid zone between domesticus and musculus). Barring such regions of the genome, it can be seen in the figure that classification of the genomic regions as musculus or non-musculus is essentially unambiguous based on our index. The figure also shows for comparison the variations of the regional proportion of SNPs alternatively fixed between wild domesticus and musculus using the same data as Harr (thick curve), and points with arrows to the significant peaks of differentiation found by this investigator. Among 10 such peaks, seven lie in regions where some of the SNP discovery strains are obviously of musculus origin. These peaks thus appear to result from the SNP ascertainment bias. However, for the proximal peak on chromosome 2 and that on chromosome 10, no mixed origin of the SNP discovery strains was detected. The results on the proximal peak of the X chromosome are ambiguous because of a gap in the resequencing data, but suggest some musculus contribution in one of the strains. The two former peaks, on chromosomes 2 and 10, and potentially the latter on the X chromosome, could thus be retained as true differentiation peaks, not suffering from the ascertainment bias. It may seem surprising that a high proportion of SNPs were found fixed between the wild domesticus and musculus when the SNPs were discovered among laboratory strains of apparently pure domesticus origin. However, if these genomic regions have undergone recent selective sweeps, most polymorphisms should be rare, which could explain this apparent paradox.
Harr (2006)  attempted to verify her findings by sequencing fragments from regions she detected as high and low differentiation in wild-derived domesticus and musculus mice, and found a significantly higher differentiation (as measured by the Gst statistics) in the former category than in the latter, in apparent agreement with her SNP analyses. We believe the agreement is real, but not for the reason given by the author. Although, as we have seen, the ascertainment bias produces many false positives among the high differentiation peaks, it should not contribute to the detection of false low differentiation peaks. Therefore, we suggest that Harr's apparent confirmation follows from her correctly identifying low differentiation regions, but not high differentiation regions as could be claimed without accounting for the ascertainment bias (with the two or three exceptions mentioned above).
1 Corresponding author.
E-mail boursot{at}univ-montp2.fr; fax 33-4-67144554. Article is online at http://www.genome.org/cgi/doi/10.1101/gr.5541806.
Bishop, C.E., Boursot, P., Bonhomme, F., Hatat, D. 1985. Most classical Mus musculus domesticus laboratory mouse strains carry a Mus musculus musculus Y chromosome. Nature 315: 70–72.[CrossRef][Medline] Britton Davidian, J., Fel-Clair, F., Lopez, J., Alibert, P., Boursot, P. 2005. Postzygotic isolation between the two European subspecies of the house mouse: Estimates from fertility patterns in wild and laboratory-bred hybrids. Biol. J. Linn. Soc. Lond. 84: 379–393.[CrossRef] Clark, A.G., Hubisz, M.J., Bustamante, C.D., Williamson, S.H., Nielsen, R. 2005. Ascertainment bias in studies of human genome-wide polymorphism. Genome Res. 15: 1496–1502. Harr, B. 2006. Genomic islands of differentiation between house mouse subspecies. Genome Res. 16: 730–737. Morin, P.A., Luikart, G., Wayne, R.K. 2004. The S.N.P. Workshop Group SNPs in ecology, evolution and conservation. Trends Ecol. Evolution 19: 208–216.[CrossRef] Pletcher, M.T., McClurg, P., Batalov, S., Su, A.I., Barnes, S.W., Lagler, E., Korstanje, R., Wang, X., Nusskern, D., Bogue, M.A. et al. 2004. Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse. PLoS Biol. 2:–e393. Raufaste, N., Orth, A., Belkhir, K., Senet, D., Smadja, C., Baird, S.J.E., Bonhomme, F., Dod, B., Boursot, P. 2005. Inferences of selection and migration in the Danish house mouse hybrid zone. Biol. J. Linn. Soc. Lond. 84: 593–616.[CrossRef] Storchova, R., Gregorova, S., Buckiova, D., Kyselova, V., Divina, P., Forejt, J. 2004. Genetic analysis of X-linked hybrid sterility in the house mouse. Mamm. Genome 15: 515–524.[Medline] Wade, C.M., Kulbokas, E.J. III, Kirby, A.W., Zody, M.C., Mullikin, J.C., Lander, E.S., Lindblad-Toh, K., Daly, M.J. 2002. The mosaic structure of variation in the laboratory mouse genome. Nature 420: 574–578.[CrossRef][Medline] Zhang, J., Hunter, K.W., Gandolph, M., Rowe, W.L., Finney, R.P., Kelley, J.M., Edmonson, M., Buetow, K.H. 2005. A high-resolution multistrain haplotype analysis of laboratory mouse genome reveals three distinctive genetic variation patterns. Genome Res. 15: 241–249.
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