Testing the accuracy of 3D automatic landmarking via genome-wide association studies.

Various advances in 3D automatic phenotyping and landmark-based geometric morphometric methods have been made. While it is generally accepted that automatic landmarking compromises the capture of the biological variation, no studies have directly tested the actual impact of such landmarking approaches in analyses requiring a large number of specimens and for which the precision of phenotyping is crucial to extract an actual biological signal adequately. Here, we use a recently developed 3D atlas-based automatic landmarking method to test its accuracy in detecting QTLs associated with craniofacial development of the house mouse skull and lower jaws for a large number of specimens (circa 700) that were previously phenotyped via a semiautomatic landmarking method complemented with manual adjustment. We compare both landmarking methods with univariate and multivariate mapping of the skull and the lower jaws. We find that most significant SNPs and QTLs are not recovered based on the data derived from the automatic landmarking method. Our results thus confirm the notion that information is lost in the automated landmarking procedure although somewhat dependent on the analyzed structure. The automatic method seems to capture certain types of structures slightly better, such as lower jaws whose shape is almost entirely summarized by its outline and could be assimilated as a 2D flat object. By contrast, the more apparent 3D features exhibited by a structure such as the skull are not adequately captured by the automatic method. We conclude that using 3D atlas-based automatic landmarking methods requires careful consideration of the experimental question.