使用微卫星和混合DNA方法对下颌前突进行全基因组关联研究。

Genome-wide association study for mandibular prognathism using microsatellite and pooled DNA method.

作者信息

Saito Fumio, Kajii Takashi S, Oka Akira, Ikuno Keiichiro, Iida Junichiro

机构信息

Department of Orthodontics, Division of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.

Section of Orthodontics, Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka, Japan.

出版信息

Am J Orthod Dentofacial Orthop. 2017 Sep;152(3):382-388. doi: 10.1016/j.ajodo.2017.01.021.

DOI:10.1016/j.ajodo.2017.01.021

PMID:28863919

Abstract

INTRODUCTION

The purpose of this study was to extend an association study from chromosome 1 to the whole genome (genome-wide association study) to find susceptibility loci of mandibular prognathism.

METHODS

Two hundred forty patients diagnosed with mandibular prognathism and 360 healthy controls of Japanese descent were recruited. The typing of microsatellites covering the whole genome was conducted using a pooled DNA method. Upon completion of the first and second screenings with pooled DNA, the positive microsatellite markers from both the first and second typings were retyped using individual-subject DNA samples to confirm the significance of allele frequency.

RESULTS

Six microsatellites (D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i) showed differences between allele frequencies of the subjects and controls at P <0.001. D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i were located on chromosomes 1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22, respectively. SSX2IP, PLXNA2, RASA2, TCF21, CALN1, and RORA were suggested as candidate genes.

CONCLUSIONS

The genome-wide association study using microsatellites suggested that 6 loci (1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22) were susceptibility regions of mandibular prognathism. The locus 1p22.3 was supported by a previous linkage analysis, and the other 5 were novel loci.

摘要

引言

本研究的目的是将一项从1号染色体扩展至全基因组的关联研究（全基因组关联研究）用于寻找下颌前突的易感基因座。

方法

招募了240例被诊断为下颌前突的患者以及360例日本血统的健康对照者。使用混合DNA方法对覆盖全基因组的微卫星进行分型。在用混合DNA完成首次和第二次筛选后，使用个体受试者的DNA样本对首次和第二次分型中的阳性微卫星标记进行重新分型，以确认等位基因频率的显著性。

结果

六个微卫星（D1S0411i、D1S1358i、D3S0810i、D6S0827i、D7S0133i和D15S0154i）在P<0.001时显示出受试者与对照者等位基因频率的差异。D1S0411i、D1S1358i、D3S0810i、D6S0827i、D7S0133i和D15S0154i分别位于1号染色体的1p22.3、1q32.2、3q23、6q23.2、7q11.22和15q22.22上。SSX2IP、PLXNA2、RASA2、TCF21、CALN1和RORA被认为是候选基因。