regulatory variation at glypican-3 underlies a major growth qtl in mice监管变化glypican-3构成一个主要增长qtl老鼠.pdfVIP

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regulatory variation at glypican-3 underlies a major growth qtl in mice监管变化glypican-3构成一个主要增长qtl老鼠.pdf

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regulatory variation at glypican-3 underlies a major growth qtl in mice监管变化glypican-3构成一个主要增长qtl老鼠

Open access, freely available online PLoS BIOLOGY Regulatory Variation at Glypican-3 Underlies a Major Growth QTL in Mice 1[ 1[* 1 2 1 3 3 Fiona Oliver , Julian K. Christians , Xiaojun Liu , Susan Rhind , Vinesh Verma , Claire Davison , Steve D. M. Brown , 3 1 Paul Denny , Peter D. Keightley 1 University of Edinburgh, Institute of Evolutionary Biology, School of Biological Sciences, Edinburgh, United Kingdom, 2 Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Centre, Roslin, Midlothian, United Kingdom, 3 Medical Research Council Mammalian Genetics Unit, Harwell, Oxfordshire, United Kingdom The genetic basis of variation in complex traits remains poorly understood, and few genes underlying variation have been identified. Previous work identified a quantitative trait locus (QTL) responsible for much of the response to selection on growth in mice, effecting a change in body mass of approximately 20%. By fine-mapping, we have resolved the location of this QTL to a 660-kb region containing only two genes of known function, Gpc3 and Gpc4, and two other putative genes of unknown function. There are no non-synonymous polymorphisms in any of these genes, indicating that the QTL affects gene regulation. Mice carrying the high-growth QTL allele have approximately 15% lower Gpc3 mRNA expression in kidney and liver, whereas expression differences at Gpc4 are non-significant. Expression profiles of the two other genes within the region are inconsistent with a factor responsible for a general effect on growth. Polymorphisms in the 39 untranslated region of Gpc3 are strong ca