Abstract
Anal atresia is a relatively common congenital malformation that occurs in about 1 out of 5000 infants, caused by abnormal hindgut development of the embryo, often associated with other developmental anomalies (e.g., Currarino, Townes–Brock, Pallister–Hall syndromes, and VATER association). Genetic analysis in human families is exceedingly difficult due to the multifactorial nature of the trait. In pigs, anal atresia occurs at a higher incidence (0.18%) than in humans. A complete genome scan (165 microsatellite markers) was performed using a backcross pedigree previously obtained by crossing affected animals from a partially inbred line, selected for a high incidence of anal atresia, with an unaffected male of a different breed (Meishan). The data set was analyzed with classical linkage (TWOPOINT) and nonparametric genetic methods (NPL, Non-Parametric Linkage, and TDT, Transmission Disequilibrium Test). Both methods support association of the trait with two loci on Chromosomes 9 and 15. GLI2 (GLI-Kruppel family member GLI2) was identified as a positional candidate gene based on comparative mapping; radiation hybrid mapping confirmed that this locus is located within the QTL region.
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Ackowledgments
This work was supported by the Fondazione Cariplo, Milan, by the Fondazione Parco Tecnologico Padano, Lodi (Italy), and by the Ministry of Education, Science, Sports and Culture (Japan), Grant-in-Aid for Scientific Research (C), 16591781, 2004. We thank Max Rothschild (US Pig Genome Coordinator, NRSP-8) for providing microsatellite primers, Paul Boettcher and Alan Archibald for the support in statistical analyses, and Susan Anderson for revision of the manuscript.
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Cassini, P., Montironi, A., Botti, S. et al. Genetic analysis of anal atresia in pigs: evidence for segregation at two main loci. Mamm Genome 16, 164–170 (2005). https://doi.org/10.1007/s00335-004-3024-6
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DOI: https://doi.org/10.1007/s00335-004-3024-6