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Genome-wide Linkage Analysis of Mandibular Prognathism in Korean and Japanese Patients

¹ Department of Orthodontics, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Outa-ku, Tokyo, 145-8515, Japan;
² Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan; and
³ Department of Orthodontics, Pusan National University, 1-10, Ami-dong, Seo-gu, Pusan, 602-739, Korea;

^* corresponding author, ituro{at}ims.u-tokyo.ac.jp

The existence of familial aggregation of mandibular prognathism (MP) suggests that genetic components play an important role in its etiology. In this study, a genome-wide linkage analysis to identify loci susceptible to MP was conducted with 90 affected sibling-pairs in 42 families, comprised of 40 Korean sibling-pairs and 50 Japanese sibling-pairs. Two non-parametric linkage analyses, GENEHUNTER-PLUS and SIBPAL, were applied and detected nominal statistical significance of linkage to MP at chromosomes 1p36, 6q25, and 19p13.2. The best evidence of linkage was detected near D1S234 (maximum Z_lr = 2.51, P = 0.0012). In addition, evidence of linkage was observed near D6S305 (maximum Z_lr = 2.23, P = 0.025) and D19S884 (maximum Z_lr = 1.93, P = 0.0089). Identification of the susceptible genes in the linkage regions will pave the way for insights into the molecular pathways that cause MP, especially overgrowth of the mandible, and may lead to the development of novel therapeutic tools.

KEY WORDS: Mandibular prognathism • linkage analysis • Korean • Japanese