Development of the diagnostic methods for the intrinsic factor of the maxillo-facial deformity using HLA and the related genes

颌面畸形、口面裂和鳃裂综合征的病因复杂，既有遗传因素，也有环境因素。然而，到目前为止，还没有证实这些疾病的特定遗传因素。这些畸形的手术和正畸治疗每次都很难取得良好的效果。因此，从预防的角度，包括临床基因治疗的角度，我们必须了解这些疾病的发病机制和相关基因。然后，作为第一步，我们确定先前在唇腭裂受试者中研究的候选基因是否与HLA- drb1 ^*1302（位于HLA的外显子2）（（实验1））和同源异构体基因DLX1和DLX2相关。（实验二）受试者：实验一为112名受试者，对照组为145名。方法：候选基因exp1采用PCR-MPH法进行基因型分析，exp2采用PCR-Direct法进行基因型分析。结果：实验1中被试总cl /P与HLA-DRB1^*1301、HLA-DRB1^*1302呈正相关（与非裂对照组相比）。同时，右cl /P与HLA-DRB1^*0802和^*1202之间存在疑似关联。在Exp.2中，我们无法在DLX1的翻译区找到共同的突变子，但在DLX2的exonl中，完全cup和（AGC）n的受试者之间存在可疑的关联。这些结果推测HLA和DLX2基因与裂裂的形成有关，并决定了裂裂的类型和位置。

The maxillo-facial deformities, orofacial clefting and branchial arch syndromes are considered to be causesd by complex etiology, including both genetic and enxironmental factors. To date, however no particular genetic factors has been confiremed for these diseases. It is very difficult to get good results of surgical and orthodontic treatment for these malformation everytime. So from a preventive point of view, including the clinical genetic treatment, we must get infomations of mechanism for causing these diseases and related genes. Then, as a first step, we determine whether the candidate genes previously studied in subjects with cleft lip, cleft palate, or both are associated with HLA-DRB1^*1302 (located exon2 iin HLA) ((Experiment 1)) and homeobox gene, DLX1 and DLX2.((Experiment 2))Subject: One hundred twelve subjects, and one hundred forty-five controls for Experiment 1. One hundred forty -two subjects, and ninety-six controls for Experiment 2Method: Genotype analysis of candidate genes was performed using PCR-MPH method for Exp.1 and PCR-Direct sequenseanalysis fo Exp.2.Result: Positive association between subjects with total-CL/P and HLA-DRB1^*1301 and HLA-DRB1^*1302 (compared with noncleft controls) was found in Experiment 1. And at the same time, there was a susupective association between subjects with right-CL/P and HLA-DRB1^*0802,and ^*1202. In Exp.2, we couldn't identify commom mutaons in translated region on DLX1, but there was a suspective association between subjects with complete-CUP and (AGC)n in exonl on DLX2.These result suspect that HLA and DLX2 gene associate for forming of clefting, and for determine the type and location of clefting.