Microsatellite genome-wi for mandibular prognathi
Keiichiro Ikuno,a Takashi S. Kajii,b Akira Oka,c Hidetoshi In
Hokkaido, Fukuoka, and Kanagawa, Japan
Introduction: Attempts have been made to identify suscep wide linkage studies, but the results of susceptibility loci association study of mandibular prognathism. Our objectiv using 23,465 microsatellite markers to detect mandibula study was based on the pooled DNA method, including 2 quent individual genotyping, with 240 experimental subjec lation. Results: Two suggestive associations on chromo 4 d PL ious 1q32 s, a
Ortho caus envi inhe tanc 9 paat ent lar iblaany any nd late nmandibular prognathism more effectively. trix protein (Matrilin-1)11 and erythrocyte membrane 12 aPostg
Devel cLectu fProfessor, Division of Oral Functional Science, Department of Orthodontics,
Graduate School of Dental Medicine, Hokkaido University, Hokkaido, Japan. 0889-5406/$36.00
Copyright 2014 by the American Association of Orthodontists.
ORIGINAL ARTICLEAn affected sibling pair analysis of mandibular prognathism in Japanese and Korean patients suggested that chromosomes 1p36, 6q25, and 19p13.2 were associated with the disease.10 Association studies of the 1p36 locus were also carried out and suggested that a cartilage maAll authors have completed and submitted the ICMJE Form for Disclosure of
Potential Conflicts of Interest, and none were reported.
Address correspondence to: Takashi S. Kajii, Section of Orthodontics, Department of Oral Growth and Development, Fukuoka Dental College, 2-15-1
Tamura, Sawara-ku, Fukuoka 814-0913, Japan; e-mail, firstname.lastname@example.org.
Submitted, February 2013; revised and accepted, January 2014.dergo orthognathic surgery despite long-term use of a chincap appliance. If orthodontists could predict whether patients have strong factors for excessive mandibular growth, they could select strategies to treat dProfessor, Division of Basic Medical Science and Molecular Medicine, Department of Molecular Life Sciences, School of Medicine, Tokai University,
Kanagawa, Japan. eProfessor, Section of Orthodontics, Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka, Japan.http:/ed by various patterns of genetic inheritance and ronmental factors. Although multiple models of ritance of the disease, including polygenic inherie,4 monogenic inheritance,5,6 autosomal-dominant treat adults with mandibular prognathism. Young tients with mandibular prognathism who are treated orthodontic clinics often receive orthopedic treatm with a chincap appliance for inhibiting mandibu bone growth in their growing period. Control of mand ular bone growth can improve the anteroposterior re tionship of the maxilla and the mandible in m patients. However, despite growth control for m years, the mandible sometimes grows excessively, a mandibular prognathism appears again in the growth period. Some patients will therefore need to u raduate student, Division of Oral Functional Science, Department of dontics, Graduate School of Dental Medicine, Hokkaido University, ido, Japan. ciate professor, Section of Orthodontics, Department of Oral Growth and opment, Fukuoka Dental College, Fukuoka, Japan. rer, Institute of Medical Science, Tokai University, Kanagawa, Japan.people.
In previous studies, this disease has been shown to be tibility genes.
At present, orthognathic surgery is frequently used to1p22.3 (D1S0411i: P 5 6.66 3 10 ) were shown, an genes; 1p22.3 flanked the region indicated by prev genome-wide association study showed that 2 loci ( of mandibular prognathism: 1p32.2 is a novel locu previous linkage analysis. (Am J Orthod Dentofacial
Mandibular prognathism, skeletal Class IIImalocclusion in orthodontics, occurs in popu-lations throughout the world but with a higher incidence in Asian populations.1 The prevalences are less than 1% in white people2 but about 10% in Japanese 3/dx.doi.org/10.1016/j.ajodo.2014.01.022de association study sm oko,d Hiroyuki Ishikawa,e and Junichiro Iidaf tibility genes of mandibular prognathism by genomeare inconsistent. There has been no genome-wide e was to perform a genome-wide association study r prognathism susceptibility regions. Methods: The steps of screening on the whole genome and subsets and 360 control subjects from the Japanese popusomes 1q32.2 (D1S1358i: P 5 4.22 3 104) and
XNA2 and SSX2IP were suggested to be candidate linkage analysis. Conclusions: The results of the .2 and 1p22.3) are likely to be susceptibility regions nd identification of 1p22.3 supports the results of p 2014;145:757-62) inheritance,7 and autosomal-recessive inheritance,8 have been suggested, it is evident that mandibular prognathism is a complex disease to which both genetic and environmental factors contribute. Recent progress in molecular genetics has enabled examination of suscep-protein band 4.1 (EPB41) were the susceptibility genes 757 758 Ikuno et alof the disease. On the other hand, a linkage study in
Brazilian families showed that 1p36, 6q25, and 19p13.2 were not associated with the disease.13 Moreover, a linkage study of 4 Hispanic families with Colombian backgrounds demonstrated that 5 loci—1p22.1, 3q26.2, 11q22, 12q13.13, and 12q23—were related to mandibular prognathism.14 Tassopoulou-Fishell et al15 suggested that myosin 1H (MYO1H) located on 12q24.11, which is near 12q23, was a susceptibility gene of the disease. Additional studies would strengthen our knowledge. There have been 2 more linkage studies on candidate loci and genes of mandibular prognathism.16,17 Genome-wide association study (GWAS) has been proposed as an alternative strategy for linkage analysis.18,19 However, there has been no GWAS of mandibular prognathism.
Microsatellites and single nucleotide polymorphisms have been used for association studies. Microsatellites are highly polymorphic and show a high degree of heterozygosity (about 70% on average) and linkage disequilibrium lengths in the 100-kilobase (kb) range.
Single nucleotide polymorphisms are thought to be genetically more stable because of a lower mutation rate, to be biallelic, and to show a low degree of heterozygosity and a short range of linkage disequilibrium (about 30 kb). Microsatellites are not likely to be evenly distributed across the genome, leaving some areas with no or little coverage.20 Therefore, most GWAS has been performed using single nucleotide polymorphisms.