Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/23456
標題: 以聚合酶連鎖反應-變性梯度凝膠電泳法診斷貓隻體染色體顯性多囊性腎病
Detection of Feline Autosomal Dominant Polycystic Kidney Disease by a PCR-DGGE Assay
作者: 翁郁中
Weng, Yu-Jong
關鍵字: Feline Autosomal Dominant Polycystic Kidney Disease
聚合酶連鎖反應-變性梯度凝膠電泳法
PCR-DGGE
貓隻體染色體顯性多囊性腎病
出版社: 生命科學院碩士在職專班
引用: 1.陳欣愉。基因PKD1突變與超音波檢測用於診斷貓多囊腎病的相關性。國立中興大學獸醫系碩士論文。台中市,中華民國,2008。 2.Adin CA, Gregory CR, Kyles AE, Cowgill L. Diagnostic predictors of complications and survival after renal transplantation in cats. Vet Surg 30: 515-521, 2001 3.Afzal AR, Jeffery S. Amplification of a 13.5-Kb region of the PKD1 gene containing the 2.5-Kb polypyrimidine tract in intron 21 facilitates mutation detection in this gene. Genet Test 5:57-59, 2001 4.Bajwa ZH, Gupta S, Warfield CA, Steinman TI. Pain management in polycystic kidney disease. Kidney international 60:1631-1644, 2001 5.Biller DS, Dibartola SP, Eaton KA, Pflueger S, Wellman ML, Radin MJ.Inheritance of polycystic kidney disease in Persian cats. Journal of heredity. 87:1-5, 1996 6.Bartges J, Willis M, Pozin J. Hypertension and renal disease. Veterinary clinics of North America: Small animal practice 26:1131-1345, 1996 7.Barthez PY, Rivier P, Begon D. Prevalence of polycystic kidney disease in Persian and Persian related cats in France. J Feline Med Surg 5: 345–347, 2003 8.Bartges J, Willis M, Pozin J. Hypertension and renal disease. Veterinary clinics of North America: Small animal practice 26:1131-1345, 1996 9.Beck C, Lavelle RB. Feline polycystic kidney disease in Persian and other cats: A prospective study using ultrasonography. Aust Vet J 79: 181–184, 2001 10.Bernsteen L, Gregory C, Kyles A, Wooldridge J, Valverde C. Renal transplantation in cats. Clinical techniques in small animal practice 15:40-45, 2000 11.Biller DS, Dibartola SP, Eaton KA, Pflueger S, Wellman ML, Radin MJ.Inheritance of polycystic kidney disease in Persian cats. Journal of heredity. 87:1-5, 1996 12.Bonazzi M, Volta A, Gnudi G, Bottarelli E, Gazzola M, Bertoni G. Prevalence of the polycystic kidney disease and renal and urinary bladder ultrasonographic abnormalities in Persian and Exotic Shorthair cats in Italy. J Feline Med Surg 9: 387-391, 2007 13.Cannon MJ, MacKay AD, Barr FJ, Rudorf H, Bradley KJ, Gruffydd-Jones TJ. Prevalence of polycystic kidney disease in Persian cats in the United Kingdom. Vet Rec 149: 409–411, 2001 14.Chauveau D, Pirson Y, Verellen-Dumoulin C, Macnicol A, Gonzalo A, Grunfeld JP. Intracranial aneurysms in autosomal dominant polycystic kidney disease. Kidney International 45:1140-1146, 1994 15.Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hiesberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, Caplan MJ. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest 114: 1433-1443, 2004 16.Cohen SN, Chang ACY, Boyer HW, Helling RB. Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA 70:3240-3244, 1973 17.Consortium TEPKD. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplication region on chromosome 16. Cell 77:881-894, 1994 18.Consortium TIPKD. Polycystic kidney disease: The complete structure of the PKD1 gene and its protein. Cell 81:289-298, 1995 19.Cooper B. Autosomal dominant polycystic kidney disease in Persian cats. Feline Prac 28: 20–21, 2000 20.Cowley BJr, Gudapaty S, Kraybill AL, Barash BD, Harding MA, Calvet JP, Gattone VH. Autosomal dominant polycystic kidney disease in the rat. Kidney Int 43:522-534, 1993 21.Delmas P, Padilla F, Osorio N. Polycystins, calcium signaling, and human disease. Biochem biophys Res Commun 322:1374-1383, 2004 22.DiBartola S. Autosomal dominant polycystic kidney disease. In: Proceedings of the 18th Annual Veterinary Medical Forum of the American College of Veterinary Internal Medicine, Seattle, American College of Veterinary Internal Medicine, 2000, pp 438–440 23.Dibartola S, Broome M, Stein B, Nixon M. Effect of treatment of hyperthyroidism on renal function in cats. JAVMA 208:875-878, 1996 24.Elliott D. Hemodialysis. Clinical techniques in small animal practice 15:136-148, 2000 25.Fischer SG, Lerman LS. Cell 16:191-200, 1979 26.Gabow PA. Autosomal dominant polycystic kidney disease-more than a renal disease. Am J Kidney Dis 22:511-512, 1993 27.Gabow PA: Autosomal dominant polycystic kidney disease. N Engl J Med 329:332-342, 1993 28.Gilbert W, Maxam AM. “The nucleotide sequence of the lac operator”. Proc Natl Acad Sci USA 70:3581-3584, 1973 29.Harris PC. Molecular basis of polycystic kidney disease; PKD1, PKD2 and PKHD1. Current opinion in nephrology and hypertension 11:309-314, 2002 30.Helps C, Tasker S, Harley R. Correlation of the feline PKD1 genetic mutation with cases of PKD diagnosed by pathological examination. Exp Mol Pathol. 83:264-268, 2007. 31.Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. Journal of the American Society of Nephrology 13:2384-2398 32.Kary Mullis Nobel Lecture, December 8, 1993 33.Kaspareit-Rittinghausen J, Rapp K, Deerberg F, Wcislo A, Messow C. Hereditary polycystic kidney disease associated with osteorenal syndrome in rats. Vet Pathol 26:195-201, 1989 34.Kimberling WJ, Kumar S, Gabow PA, Kenyon JB, Connolly CJ, Somlo S. Autosomal dominant polycystic kidney disease: Localization of the second gene to chromosome 4q13-q23. Genomics 18:467-472, 1993 35.Lieske JC, Toback FG. Autosomal dominant polycystic kidney disease. Am J Soc Nephrol 3:1442-1450, 1993 36.Lyons LA, Biller DS, Erdman CA, Lipinski MJ, Young AE, Roe BA, Qin B, Grahn RA. Feline polycystic kidney disease mutation identified in PKD1. J Am Soc Nephrol 15:2548-2555, 2004 37.Maxam AM, Gilbert W. “ A new method for sequencing DNA”. Proc Natl Acad Sci USA 74:560-564, 1977 38.McAuliffe L, Ellis RJ, Lawes JR, Ayling RD, Nicholas RA. 16S rDNA PCR and denaturing gradient gel electrophoresis; a single generic test for detecting and differentiating Mycoplasma species. J Med Microbiol. 54:731-739, 2005 39.McGrath J, Somol S, Makova S. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114:61-73, 2003 40.Muyzer G, de Waal EC, Uitterlinden AG. Profiling of complex microbial population by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA. Appl Environ Microbiol 59:695-700, 1993 41.Muyzer G, Smalla K. Application of denaturing gradient gel electrophoresis (DGGE) and temperature gradient gel electrophoresis (TGGE) in microbial ecology. Antonie van Leeuwenhoek 73:127-141, 1998 42.Myers RM, Fischer SG, Lerman LS, Maniatis T. Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresis. Nucleic acid research 13:3131-1345, 1985 43.Nauli SM, Alenghat FJ, Luo Y. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129-137, 2003 44.Peral B, Gamble V, San Millan JL, Strong C, Sloane-Stanley J, Moreno F, Harris PC. Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion. Hum Mol Genet 4:569-574, 1995 45.Peters DJ, Spruit L, Saris JJ, Ravine D, Sandkuijl LA, Fossdal R, Boersma J, van Eijk R, Norby S, Constantinou-Deltas CD. Chromosome 4 localization of a second gene for autosomal dominant polycystic kidney disease. Nat Genet 5:359-362, 1993 46.Piontek KB, Germino GG. Murine Pkd1 intron 21 and 22 lack the extreme polypyrimidine bias present in human PKD1. Mamm genome 10:194-196, 1999 47.Pirson Y, Chauveau D, Torres V. Management of cerebral aneurysms in autosomal dominant polycystic kidney disease. Journal of the American Society of Nephrology 13:269-276, 2002 48.Polzin D, Osborne C, Ross S, Jacob F. Dietary menagement of feline chronic renal failure: Where are we now? In what direction are we headed? Journal of feline medicine and surgery 2:75-82, 2000 49.Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. “Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase”. Science 239:487-491, 1988 50.Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. “Enzymatic amplification of beta-globin genomic sequence and restriction site analysis for diagnosis of sickle cell anemia”. Science 230:1350-1354, 1985 51.Sanger F, Coulson AR.“A rapid method for determining sequence in DNA by primed synthesis with DNA polymerase”. J Mol Biol 94:441-448, 1975 52.Sanger F, Nicklen S, Coulson AR. “DNA sequencing with chain-terminating inhibitors”. Proc Natl Acad Sci USA 74:5463-5467, 1977 53.Schafer K, Gretz N, Bader M, Oberbaumer I, Eckardt KU, Kriz W, Bachmann S. Characterization of the Han:SPRD rat model for hereditary polycystic kidney disease. Kidney Int 46:134-152, 1994 54.Adin CA, Gregory CR, Kyles AE, Cowgill L. Diagnostic predictors of complications and survival after renal transplantation in cats. Vet Surg 30: 515-521, 2001 55.Cowley BJr, Gudapaty S, Kraybill AL, Barash BD, Harding MA, Calvet JP, Gattone VH. Autosomal dominant polycystic kidney disease in the rat. Kidney Int 43:522-534, 1993 56.Son A, Dhirapong A, Dosev DK, Kennedy IM, Weiss RH, Hristova KR. Rapid and quantitative DNA analysis of genetic mutations for polycystic kidney disease (PKD) using magnetic/luminescent nanoparticles. Anal Bioanal Chem 390:1829-1835, 2008 57.Torres VE, Harris PC. Mechanism of disease: Autosomal dominant and recessive polycystic kidney disease. Nat Clin Prac Nephrol 2:40-55, 2006 58.Turco AE, Rossetti S, Bresin E, Corra S, Gammaro L, Maschio G, Pignatti PF. A novel nonsense mutation in the PKD1 gene (C3817T) in a large three-generation Italian family. Hum Mol Genet 4:1331-1335, 1995 59.Walter J, Tannock GW, Tilsala-Timisjarvi A, Rodtong S, Loach DM, Munro K, Alatossava T. Detection and identification of gastrointestinal Lactobacillus species by using denaturing gradient gel electrophoresis and species-specific PCR primers. Appl Environ Microbio 66:297-303, 2000 60.Wang S, Zhang J, Nauli SM, Li X, Starremans PG, Luo Y, Roberts KA, Zhou J. Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia. Mol Cell Biol 27: 3241-3252, 2007 61.Watnick TJ, Gandolph MA, Weber HNH, Germino G. Gene conversion is a likely cause of mutation in PKD1. Hum Mol Genet 7:1239-1243, 1998 62.Watnick TJ, Piontek KB, Cordal TM, Weber H, Gandolph MA, Qian F, Lens XM, Neumann HP, Germino G. An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection. Hum Mol Genet 6:1473-1481, 1997 63.Wei W, Hackmann K, Xu H, Germino G, Qian F. Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene. J Biol Chem 282: 21729-21737, 2007 64.Wilson PD. Polycystic kidney disease. N Engl J Med 350:151-164, 2004 65.Wu G. Current advances in molecular genetics of autosomal-dominant polycystic kidney disease. Current opinion in nephrology and hypertension. 10:177-188, 2001
摘要: 變性梯度凝膠電泳法用以診斷突變的原理是根據DNA片段在變性濃度梯度的聚丙醯酰氨(polyacrylamide)凝膠上有不同速度的移動,此不同移動速度的原理是序列排列決定的,初始基因片段的移動速度是根據分子量,後來在凝膠的特殊位置達到變性濃度和熔解溫度時,部份雙股DNA會局部打開成單股DNA,這些有分枝的雙股DNA頓時移動會停滯,在DNA片段加入富含GC序列的GC鉗是提升變性凝膠電泳法診斷率的關鍵,GC鉗的加入是基因片斷中最穩定的區段,從而另外較鬆散的區段可以方便DGGE做鑑別診斷。貓隻的多囊性腎病與貓的PKD1基因有關,此基因負責製造polycystin,polycystin是一種類似穿膜受體的蛋白質。一個C/A的核苷酸顛換造成一個提早形成的終止密碼,此核苷酸轉換的位置發生在貓隻PKD1基因的第29個外顯子。貓隻的PKD是體染色體顯性遺傳,囊泡在一出生即產生,一開始很小逐漸變大,囊泡的大小從很小到數公分。逐漸變大的囊泡傷害正常的腎臟組織最終導致腎臟衰竭,貓隻的PKD是貓隻最常見的遺傳疾病,侵犯了全世界約38%的波斯貓,10個月以上的貓隻超音波的診斷率為98%。我們收集了2006年十二月至2008年十二月間至中興大學獸醫教學醫院就診的123貓隻,其中78隻為波斯貓,14隻金吉拉貓、10隻短毛家貓、5隻美國短毛貓、5隻喜馬拉雅貓、3隻布偶貓、2隻孟加拉貓、1隻英國短毛貓、1隻異國短毛貓和1隻暹邏貓。共有56隻貓進行腹腔超音波學檢查,包括膀胱、雙側腎臟及肝臟,結果顯示有12隻貓罹患ADPKD。這12隻貓的血液同時進行限制切段長度基因多型性(restriction fragment length polymorphism, RFLP)及聚合酶連鎖反應-變性梯度凝膠電泳法(PCR-DGGE)兩種分子生物技術診斷ADPKD,共有10隻貓隻經由這兩種分子生物技術檢測出ADPKD。代表有2隻貓隻的ADPKD並不是發生在PKD1基因的第29個外顯子的點突變,這個結果暗示可能有其他基因突變會造成體染色體顯性多囊性腎病。RFLP和PCR-DGGE診斷體染色體顯性多囊性腎病的正確率是一樣的,而且PCR-DGGE比RFLP能診斷出PKD1基因以外的點突變,這是所有文獻報導第一次將PCR-DGGE提供診斷體貓隻染色體顯性多囊性腎病,我們需要更多的病例來做此研究。
The detection of mutations by DGGE is based on the sequence-dependent electrophoretic mobility of double-stranded DNA fragments in a polyacrylamide gel that contains a linear denaturing gradient. Initially, the migration rate of the fragment depends on its molecular weight. However, at a specific point in the gel, the combination of denaturant concentration and temperature equals the Tm of the lower melting domain, resulting in a partially single-stranded fragment. The mobility of these branched fragments in the polyacrylamide is abruptly retarded. The addition of an artificial GC-rich sequence, a so-called GC-clamp, to DNA fragments has been a major improvement in DGGE methodology. Such a GC-clamp serves as the most stable part of the fragment and allows the detection of sequence variation in the remainder of the fragment. In PKD affected cats, the disease was linked to the feline PKD1 gene, coding polycystin, a protein similar to the transmembrane receptor. A C/A transversion resulting in a premature stop codon was identified in exon 29 of the feline PKD1 gene. PKD is inherited as an autosomal dominant trait. Cysts are present from birth, but start out small, slowly increasing in size. Cysts can range from very small to several centimeters in diameter. The increasing size of the cysts damage the normal kidney tissue, eventually causing kidney failure. Feline PKD is the most prevalent inherited disease of cats. It affects 38% of Persian cats worldwide. Ultrasound diagnosis is 98% accurate after approximately 10 months of age. We collected the cats submitted to NCHU VMTH from December 2006 to December 2008. One hundred and twenty-three cats were involved, consisting of 78 Persians, 14 Chinchilla, 11 Domestic Shorthair, 5 Himalaya, 6 American Shorthair, 3 Ragdoll, 3 Bengal, 1 Irish Shorthair, 1 Exotic Shorthair and 1 Siamese. Ultrasonographic examination of urinary bladder, both kidneys and liver was performed in 56 cats. ADPKD was diagnosed in 12 of the 58 cats. The blood of the 12 cats with ADPKD was obtained. Restriction fragment length polymorphism (RFLP) analysis and polymerase chain reaction - denaturing gradient gel electrophoresis (PCR-DGGE) assay were performed to compare the diagnostic accuracy between these two genetic biotechnology. Only 10 of the 12 ADPKD blood samples were positive of RFLP analysis and PCR-DGGE assay. Two ADPKD affected cats diagnosed by ultrasonography were absent of the point mutation in exon 29. Other mutations may contribute to feline ADPKD. The accuracy of RFLP and PCR-DGGE was the same. PCR-DGGE can detect other single nucleotide polymorphism than PKD1. This is the first study to apply PCR-DGGE to detect PKD1 gene. More cases are needed for further evaluation of this methodology to detect PKD1 gene.
URI: http://hdl.handle.net/11455/23456
其他識別: U0005-2708200911563300
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2708200911563300
Appears in Collections:生命科學系所

文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.