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ENU LARGE-SCALE MUTAGENESIS AND QUANTITATIVE TRAIT LINKAGE (QTL) ANALYSIS IN MICE: NOVEL TECHNOLOGIES FOR SEARCHING POLYGENETIC DETERMINANTS OF CRANIOFACIAL ABNORMALITIES

¹ The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Box 951668, CHS B3-087, Los Angeles, CA 90095; ² Department of Pathology and Laboratory Medicine, ³ Department of Medicine, and ⁴ Department of Microbiology and Molecular Genetics, UCLA, Los Angeles, CA; ⁵ Department of Orthopedic Surgery, UCLA School of Medicine, Los Angeles, CA; ⁶ Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH;

^* corresponding author, ichiron{at}dent.ucla.edu

Discrepancies in size and shape of the jaws are the underlying etiology in many orthodontic and orthognathic surgery patients. Genetic factors combined with environmental interactions have been postulated to play a causal or contributory role in these craniofacial abnormalities. Along with the soon-to-be-available complete human and mouse genomic sequence data, mouse mutants have become a valuable tool in the functional mapping of genes involved in the development of human maxillofacial dysmorphologies. We review two powerful methods in such efforts: N-ethyl-N-nitrosourea (ENU) large-scale mutagenesis and quantitative trait linkage (QTL) analysis. The former aims at producing a plethora of novel variants of particular trait(s), and ultimately mapping the point mutations responsible for the appearance of these new traits. In contrast, the latter applies intensive breeding and mapping techniques to identify multiple loci (and, subsequently, genes) contributing to the phenotypic difference between the tested strains. A prerequisite for either approach to studying variations in the traits of interest is the application of effective mouse cephalometric phenotype analysis and rapid DNA mapping techniques. These approaches will produce a wealth of new data on critical genes that influence the size and shape of the human face.

Key words. Mice, ENU mutagenesis, chromosomal mapping, quantitative trait locus analysis, craniofacial anomalies

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