本文選題：恒河猴川西亞種　切入點(diǎn)：II型糖尿病　出處：《四川抗菌素工業(yè)研究所》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：II型糖尿�。═2DM）是環(huán)境和遺傳共同作用的結(jié)果，家族史、肥胖、年齡、高脂飲食、缺乏運(yùn)動(dòng)和壓力等均為危險(xiǎn)因素。研究T2DM的發(fā)病機(jī)制以及潛在的治療手段，需要合適的T2DM動(dòng)物模型。目前使用最廣泛的是嚙齒類動(dòng)物T2DM模型，但是由于其與人親緣關(guān)系遠(yuǎn)，機(jī)體生理特征差別大，因此作為模型研究人類疾病并不能很準(zhǔn)確模擬患者的狀況。非人靈長類動(dòng)物由于在種屬關(guān)系上與人接近，被認(rèn)為是最接近人類的疾病研究模型動(dòng)物。已有的報(bào)道提示，恒河猴自發(fā)T2DM發(fā)病情況與人十分相似，疾病的發(fā)生發(fā)展過程及臨床表現(xiàn)與人T2DM相似。但是，恒河猴自發(fā)T2DM的遺傳因素研究未見報(bào)道。 我們采用靜脈葡萄糖耐量試驗(yàn)、BMI、空腹血糖、空腹胰島素以及糖化血紅蛋白等指標(biāo)對50只在相同環(huán)境條件下飼養(yǎng)的恒河猴進(jìn)行監(jiān)測，發(fā)現(xiàn)了8只T2DM恒河猴。之后，采用微衛(wèi)星分子標(biāo)記法（SSR）對發(fā)生糖尿病和未發(fā)生糖尿病的恒河猴進(jìn)行了親緣關(guān)系分析，，同時(shí)采用直接測序法研究了Genbank中的恒河猴單核苷酸多態(tài)性（SNP）位點(diǎn)KCNJ11（rs196622309）、HHEX/IDE（rs195115827，rs194506087）、ADIPOQ（rs196717151，rs196591545，rs196142463，rs196060906，rs195222188）的基因多態(tài)性與疾病發(fā)生的關(guān)聯(lián)性。 結(jié)果顯示，糖尿病恒河猴個(gè)體之間的親緣關(guān)系較近，與不易感恒河猴之間的親緣關(guān)系較遠(yuǎn)。8個(gè)SNP位點(diǎn)與關(guān)聯(lián)性分析結(jié)果表明，ADIPOQ（rs196717151）、ADIPOQ（rs195222188）、HHEX/IDE（rs195115827）、ADIPOQ（rs196060906）4個(gè)位點(diǎn)的聚合酶鏈?zhǔn)椒磻?yīng)在易感糖尿病的恒河猴中不能得到目的條帶，故未進(jìn)行下一步的測序分析。KCNJ11（rs196622309）、HHEX/IDE （rs194506087）、ADIPOQ（rs196142463）3個(gè)SNP位點(diǎn)在T2DM和不易感T2DM恒河猴中均只出現(xiàn)了同一種基因型，沒有出現(xiàn)多態(tài)性。ADIPOQ（rs196591545）在T2DM和不易感T2DM恒河猴中都出現(xiàn)了GG、GC、CC三種基因型，表現(xiàn)出多態(tài)性。四個(gè)位點(diǎn)的序列都與Genbank中的序列一致。rs196591545C/G位點(diǎn)的基因型頻率和等位基因頻率，在T2DM和不易感T2DM恒河猴中分別為GG0.375/0.1428、GC0.375/0.7143、 CC0.25/0.1428、 G0.5625/0.5、 C0.4375/0.5。此外，在rs195522309位點(diǎn)下游發(fā)現(xiàn)了一個(gè)新的SNP，在T2DM和不易感T2DM恒河猴中都表現(xiàn)出多態(tài)性，產(chǎn)生CC、GC、GG三種基因型。 易感糖尿病恒河猴的親緣關(guān)系較近，可能有共同的遺傳特征。但由于樣本量太少，還沒有發(fā)現(xiàn)SNP與恒河猴T2DM的關(guān)聯(lián)性。
[Abstract]:Type II diabetes mellitus (T2DM) is the result of environmental and genetic interaction. Family history, obesity, age, high-fat diet, lack of exercise and stress are all risk factors. A suitable animal model of T2DM is needed. At present, the rodent model of T2DM is widely used. Therefore, the study of human diseases as a model can not accurately simulate the condition of patients. Non-human primates are considered to be the closest model animals to human disease because they are closely related to human species. The incidence of spontaneous T2DM in rhesus monkey is very similar to that in human, and the process and clinical manifestation of the disease are similar to that of human T2DM. However, the genetic factors of spontaneous T2DM in rhesus monkey have not been reported. We monitored 50 rhesus monkeys fed under the same environment with BMI, fasting blood glucose, fasting insulin and glycosylated hemoglobin, and found 8 T2DM rhesus monkeys. The genetic relationship of rhesus monkeys with and without diabetes mellitus was analyzed by microsatellite molecular marker method (SSRs). At the same time, direct sequencing was used to study the association between the genetic polymorphisms of Rhesus Monkey single nucleotide Polymorphic SNPs (KCNJ11622309) locus KCNJ11622309, rs195115827rs194506087rs194506087rs196717151rs196591545rs196142463rs196060906rs195222188). The results showed that the genetic relationship between individuals of diabetic rhesus monkey was close. The results of 8 SNP loci and association analysis showed that the four loci of ADIPOQN rs1952221888 HHEX / IDEN rs195115827) could not be detected in the rhesus monkey susceptible to diabetes mellitus by polymerase chain reaction (PCR) at 4 loci of the rhesus monkey, which was susceptible to diabetes mellitus (Rhesus mulatta), and the results showed that there were no bands of polymerase chain reaction at the 4 loci of ADIPOQN rs196060906 in the rhesus monkey susceptible to diabetes mellitus (Rhesus mulatta). Therefore, no further sequencing analysis was carried out. KCNJ11rs196622309 (HHEX / Ide rs194506087rs194506087rs196142463) three SNP loci had only the same genotype in T2DM and non-susceptible T2DM rhesus monkeys, and no polymorphism. ADIPOQRs196591545) in T2DM and non-susceptible T2DM rhesus monkeys, there were three genotypes of GGGCCC in both T2DM and non-susceptible T2DM rhesus monkeys. The sequence of the four loci is consistent with the sequence of Genbank. The genotype frequency and allelic frequency of the locus G in T2DM and non-susceptible T2DM rhesus monkeys are G0.375 / 0.1428 GC0.3750.7143, CC0.25 / 0.1428, G0.5625- / 0.5, C0.4375- / 0.5respectively. A new SNPs was found downstream of the rs195522309 locus, which showed polymorphism in both T2DM and non-susceptible T2DM rhesus monkeys, and produced three genotypes of CCGCG-GG. The genetic relationship of susceptible diabetic rhesus monkeys is close, which may have the same genetic characteristics. However, because of the small sample size, no association between SNP and Rhesus monkey T2DM has been found.
【學(xué)位授予單位】：四川抗菌素工業(yè)研究所
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1

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