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研究生:江郁玲
研究生(外文):Jiang, Yuling
論文名稱:豬 INSL3、AR 基因之多態性及其與隱睪症之關係
論文名稱(外文):The polymorphisms in INSL3, AR genes and their relationship with cryptorchidism in pigs
指導教授:陳銘正陳銘正引用關係
指導教授(外文):Chen, Mingcheng
口試委員:林佳靜陳威戎劉秀洲
口試委員(外文):Lin, ChaichingChen, WeijungLiu, Hsiuchou
口試日期:2012-07-18
學位類別:碩士
校院名稱:國立宜蘭大學
系所名稱:動物科技學系碩士班
學門:農業科學學門
學類:畜牧學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:105
中文關鍵詞:隱睪症第三型類胰島素因子雄性素接受體高解析度熔解法單股核甘酸構形多型性
外文關鍵詞:cryptorchidismINSL3ARHRMSSCPpig
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雄性肉豬在出生三週至一個月會進行去勢,避免肥育後產生公豬臭,影響豬肉風味與價值。患有隱睪症者之肉豬需進行腹腔手術才可以完全去勢,手術麻煩也有風險存在。目前約有 1-12% 之雄性肉豬患有隱睪症,對養豬產業有嚴重之影響,因隱睪症為性別限制性狀,母豬可能帶有隱睪症基因,故可利用基因選種來減少隱睪症比率。第三型類胰島素因子 (Insulin-like factor 3, INSL3) 及雄性素 (Androgen),分別為跨腹期與腹股陰囊期控制睪丸下降之主要內泌素,且 INSL3 基因與雄性素接受體 (Androgen receptor) 基因 CAG-repeat 之多態性與人類隱睪症有關,因此本試驗應用單股核苷酸多型性 (Single strand conformation polymorphism, SSCP) 與高解析度熔點 (High resolution melting, HRM) 法檢測豬 INSL3 及AR基因之多態性,並分析其與豬隱睪症之相關性。試驗 1 以豬緊迫敏感基因為例,建立 SSCP 與 HRM 技術,結果顯示 SSCP 與 HRM 皆可準確辨別一個鹼基之突變。試驗 2 調查台灣豬隱睪症之比率及對肉品市場與養豬農民之影響,結果發現肉品市場豬隱睪症之發現率約 0.23%,而豬隱睪症對豬農之損失較大,對肉品市場較無影響。試驗 3-6 為以 SSCP、 HRM 分析健康與患有隱睪症公豬之樣品,結果顯示 INSL3 外顯子 1 (exon1)、 外顯子 2 (exon2) 及 AR CAG-repeat 並無多態性,而在 INSL3 啟動子 (promoter) 有 2 個 SNP 點,分別為 G-224A 與 A-164C ,分析 92 頭健康與 92 頭患有隱睪症公豬對偶基因型頻率,健康豬與隱睪豬 G-224A 之GG 與 AG 基因型基因型頻率皆為 84% 與 16%,G 與 A 之對偶基因頻率分別為0.92 與0.08;健康 A-164C 之基因型 AA、AC 與 CC之頻率分別為 26、34 與 40%;A 與 C 之對偶基因頻率分別為 0.43 與 0.57 %;隱睪豬 A-164C 之基因型 AA、AC 與 CC 之頻率分別為 21 、 45 與 34%,A 與 C 之對偶基因頻率分別為 0.44 與 0.56。G-224A 與 A-164C 這 2 個 SNP 點與隱睪症無關且無品種之差異。將 30 頭隱睪豬樣品 INSL3 基因之內顯子 1 (intron1) 定序,並無任何鹼基之變異。綜上所述,AR 基因之 CAG-repeat 並無任何變異,INSL3 基因之 SNP 與豬隱睪症無關。
Three- to four-week-old male piglets are castrated to prevent boar taint in post-puberty that will cause poor quality and low value of the pork. Cryptorchid pigs need to be castrated by abdominal surgery, which is associated with complications and viability loss. Between 1% and 12% of full-term male pigs suffer from cryptorchidism, which can have a serious affect on the pig industry. Cryptorchidism is a sex-limited abnormality. Thus, screening sows that carry the cryptorchid gene, and selectively removing them by culling, is one strategy for lowering the frequency of cryptorchidism in domesticated pig livestock. Insulin-like factor 3 (INSL3) and androgens are major hormones that regulate testis descent during the transabdominal phase and inguinoscrotal phase, respectively. Some studies indicate that INSL3 and androgen receptor (AR) gene CAG-repeat polymorphisms are associated with cryptorchidism in humans. The present study applied single-strand conformation polymorphism (SSCP) and high-resolution melting (HRM) to detect INSL3 and AR gene polymorphisms and their relationship with cryptorchidism in pigs. In Experiment 1, we used the porcine stress syndrome (PSS) gene as a model to establish the SSCP and HRM techniques; the results showed that we could correctly differentiate a single base variation by SSCP and HRM. In Experiment 2, we surveyed the percentage of porcine cryptorchidism and the influence of cryptorchidism on meat markets and pig farmers in Taiwan. The percentage of cryptorchidism was 0.23% in the meat markets and the influence of porcine cryptorchidism was greater than the meat markets for pig farmers. Experiments 3–6, utilized SSCP and HRM to examine the genomic DNA samples of healthy and cryptorchid pigs and screen for polymorphisms of INSL3 and AR gene CAG-repeats. There were no polymorphisms in exons 1 and 2 of INSL3, or in the AR gene CAG-repeat. However, two single-nucleotide polymorphisms (SNPs) were detected in the INSL3 promoter region (G-224A and A-164C). We analyzed the genotype and allele frequencies of 92 healthy and 92 cryptorchid boars. The GG and AG genotype frequencies of the G-224A SNP in healthy and cryptorchid pigs were 84% and 16%, respectively. This accounted for 0.92 and 0.08 gene frequencies for the G and A alleles. The A-164C genotype frequencies of AA, AC, and CC in healthy pigs were 26%, 34%, and 40%, respectively, which accounted for 0.43 and 0.57 gene frequencies for the A and C alleles. The frequencies of AA, AC, and CC were 21%, 45%, 34%, and the A and C allele frequencies were 0.44 and 0.56 in cryptorchid pigs. Furthermore, there were no differences in the frequencies of INSL3 genotypes and alleles between pig breeds. We also sequenced the INSL3 gene introns of 30 cryptorchid pigs and found no base variation. In conclusion, cryptorchid pigs do not exhibit significant variation in either the INSL3 or AR genes. This is in contrast to the case in humans, and suggests that, as yet, undiscovered genetic changes underlie testicular abnormalities in livestock pig breeds.
中文摘要 I
英文摘要 III
致謝 V
表次 X
圖次 XI
附次 XIII
壹、 前言 1
貳、文獻檢討 3
一、 睪丸 3
(一) 睪丸之構造 3
(二) 睪丸之功能 5
1. 賽透力細胞 5
2. 來狄吉細胞 6
二、睪丸下降機制 6
(一) 跨腹期 7
(二) 腹股陰囊期 8
三、 隱睪症 8
(一) 病因學 9
(二) 隱睪症對發身後公豬之影響 10
1. 生精細管 10
2. 間質組織 11
(三) 候選基因 11
1. 第三型類胰島素因子基因 11
2. 第二型鬆弛素家族胜肽接受體基因 13
3. 雄性素接受體基因 13
4. 苗勒氏管抑制素基因 15
5. 動情素接受體基因 15
6. 其他候選基因 16
四、基因多型性預先篩選技術 17
(一) 單股核甘酸構形多型性 17
(二) 變性梯度膠體電泳 19
(三) 變性高效液相層析 19
(四) 高解析度熔點分析法 20
參、材料與方法 21
一、試驗流程 21
二、試驗動物來源 21
(一) 隱睪豬樣品 21
(二) 對照組樣品 21
三、核酸萃取 21
(一) 組織DNA 之萃取 21
(二) 精液DNA 之萃取 25
四、核酸定量 26
五、引子之設計與聚合酶鏈鎖反應 26
(一) CRC 引子之設計與聚合酶鏈鎖反應 26
(二) INSL3引子之設計與聚合酶鏈鎖反應 27
(三) AR CAG-repeat 區域引子之設計與聚合酶鏈鎖反應 28
六、單股核甘酸構形多型性 (SSCP) 28
(一) 膠體溶液之配製 28
(二) 鑄膠 28
(三) PCR產物之變性處理與注入 28
(四) 電泳與染色 29
七、高解析度熔點分析法 (HRM)29
八、限制酶切割 29
(一) 豬 CRC 基因 29
(二) 豬 INSL3 基因 30
九、定序 30
十、統計分析 30
肆、結果 34
一、建立 SSCP 與 HRM 分析技術-以豬隻緊迫敏感基因為例 34
二、豬隱睪症對於肉品市場之影響 40
三、應用 SSCP 與 HRM 分析 INSL3 及 AR 基因多型性 43
四、INSL3 與 AR 基因 CAG-repeat 之核酸定序 52
五、 建立 G-224A 與 A-164C 之基因型檢驗法 54
六、 G-224A 與 A-164C 基因頻率與隱睪症之關係 62
伍、討論 66
陸、結論 70
柒、參考文獻 71
捌、 附錄 80
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