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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊偉勛 | |
| dc.contributor.author | Rung-Shan Lee | en |
| dc.contributor.author | 李容姍 | zh_TW |
| dc.date.accessioned | 2021-06-13T01:04:33Z | - |
| dc.date.available | 2007-08-08 | |
| dc.date.copyright | 2007-08-08 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-23 | |
| dc.identifier.citation | 1.Felson, D.T., et al., The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum, 1987. 30(8): p. 914-8.
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Uitterlinden, A.G., et al., Adjacent genes, for COL2A1 and the vitamin D receptor, are associated with separate features of radiographic osteoarthritis of the knee. Arthritis Rheum, 2000. 43(7): p. 1456-64. 41. Mustafa, Z., et al., Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis. Rheumatology (Oxford), 2000. 39(3): p. 299-306. 42. Jakkula, E., et al., The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis. Osteoarthritis Cartilage, 2005. 13(6): p. 497-507. 43. Valdes, A.M., et al., Association study of candidate genes for the prevalence and progression of knee osteoarthritis. Arthritis Rheum, 2004. 50(8): p. 2497-507. 44. Mabuchi, A., et al., Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints. J Hum Genet, 2001. 46(8): p. 456-62. 45. Vilim, V., et al., Serum cartilage oligomeric matrix protein reflects the presence of clinically diagnosed synovitis in patients with knee osteoarthritis. Osteoarthritis Cartilage, 2001. 9(7): p. 612-8. 46. Vilim, V., et al., Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage, 2002. 10(9): p. 707-13. 47. Petersson, I.F., et al., Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint. Br J Rheumatol, 1998. 37(1): p. 46-50. 48. Gleghorn, L., et al., A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis. Am J Hum Genet, 2005. 77(3): p. 484-90. 49. Song, R.H., et al., Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum, 2007. 56(2): p. 575-85. 50. Appleton, C.T., et al., Global analyses of gene expression in early experimental osteoarthritis. Arthritis Rheum, 2007. 56(6): p. 1854-68. 51. Keen, R.W., et al., Association of early osteoarthritis of the knee with a Taq I polymorphism of the vitamin D receptor gene. Arthritis Rheum, 1997. 40(8): p. 1444-9. 52. Solovieva, S., et al., Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women. Arthritis Res Ther, 2006. 8(1): p. R20. 53. Meulenbelt, I., et al., A genetic association study of the IGF-1 gene and radiological osteoarthritis in a population-based cohort study (the Rotterdam Study). Ann Rheum Dis, 1998. 57(6): p. 371-4. 54. Min, J.L., et al., Association of the Frizzled-related protein gene with symptomatic osteoarthritis at multiple sites. Arthritis Rheum, 2005. 52(4): p. 1077-80. 55. Meulenbelt, I., et al., Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes. Eur J Hum Genet, 2006. 14(12): p. 1280-7. 56. Min, J.L., et al., Mutation analysis of candidate genes within the 2q33.3 linkage area for familial early-onset generalised osteoarthritis. Eur J Hum Genet, 2007. 15(7): p. 791-9. 57. Liu, Y.F., et al., Type II collagen gene variants and inherited osteonecrosis of the femoral head. N Engl J Med, 2005. 352(22): p. 2294-301. 58. Prockop, D.J., Mutations that alter the primary structure of type I collagen. The perils of a system for generating large structures by the principle of nucleated growth. J Biol Chem, 1990. 265(26): p. 15349-52. 59. Valdes, A.M., et al., Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheum, 2007. 56(1): p. 137-46. 60. Carlson, K.M., et al., Precocious osteoarthritis in a family with recurrent COL2A1 mutation. J Rheumatol, 2006. 33(6): p. 1133-6. 61. Tchetina, E.V., G. Squires, and A.R. Poole, Increased type II collagen degradation and very early focal cartilage degeneration is associated with upregulation of chondrocyte differentiation related genes in early human articular cartilage lesions. J Rheumatol, 2005. 32(5): p. 876-86. 62. Henrotin, Y., et al., Type II collagen peptides for measuring cartilage degradation. Biorheology, 2004. 41(3-4): p. 543-7. 63. Ala-Kokko, L., et al., Single base mutation in the type II procollagen gene (COL2A1) as a cause of primary osteoarthritis associated with a mild chondrodysplasia. Proc Natl Acad Sci U S A, 1990. 87(17): p. 6565-8. 64. Korkko, J., et al., Widely distributed mutations in the COL2A1 gene produce achondrogenesis type II/hypochondrogenesis. Am J Med Genet, 2000. 92(2): p. 95-100. 65. Chan, D., et al., A COL2A1 mutation in achondrogenesis type II results in the replacement of type II collagen by type I and III collagens in cartilage. J Biol Chem, 1995. 270(4): p. 1747-53. 66. Richards, A.J., et al., Missense and silent mutations in COL2A1 result in Stickler syndrome but via different molecular mechanisms. Hum Mutat, 2007. 28(6): p. 639. 67. Van Der Hout, A.H., et al., Occurrence of deletion of a COL2A1 allele as the mutation in Stickler syndrome shows that a collagen type II dosage effect underlies this syndrome. Hum Mutat, 2002. 20(3): p. 236. 68. Tiller, G.E., et al., Dominant mutations in the type II collagen gene, COL2A1, produce spondyloepimetaphyseal dysplasia, Strudwick type. Nat Genet, 1995. 11(1): p. 87-9. 69. Chan, D., T.K. Taylor, and W.G. Cole, Characterization of an arginine 789 to cysteine substitution in alpha 1 (II) collagen chains of a patient with spondyloepiphyseal dysplasia. J Biol Chem, 1993. 268(20): p. 15238-45. 70. Bogaert, R., et al., An amino acid substitution (Gly853-->Glu) in the collagen alpha 1(II) chain produces hypochondrogenesis. J Biol Chem, 1992. 267(31): p. 22522-6. 71. Bleasel, J.F., et al., Type II procollagen gene (COL2A1) mutation in exon 11 associated with spondyloepiphyseal dysplasia, tall stature and precocious osteoarthritis. J Rheumatol, 1995. 22(2): p. 255-61. 72. Tiller, G.E., et al., Tandem duplication within a type II collagen gene (COL2A1) exon in an individual with spondyloepiphyseal dysplasia. Proc Natl Acad Sci U S A, 1990. 87(10): p. 3889-93. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29322 | - |
| dc.description.abstract | 目標：骨關節炎（Osteoarthritis , OA）是一種在人類當中非常常見的關節疾病，目前，我們發現了二個有家族性早發型骨關節炎的家族，從這兩個家族的圖譜來觀察，會發現他們的遺傳模式，符合孟德爾遺傳定律當中的體染色體顯性遺傳。本論文研究的目的是想藉由探索COL2A1基因是否有突變，來建立台灣家族性早發型骨關節炎的基因診斷及遺傳諮詢平台，若是這個模式能夠成功且準確的檢測出致病基因，以後，對於有類似情形的病患，我們就可以幫他們做基因的檢測，給予適當的醫療介入及遺傳諮詢。
方法：我們收集了兩個有家族性早發型骨關節炎的家族，總共23位家屬萃取其白血球的DNA。將這些受試者的檢體，利用PCR及核酸定序法，來分析COL2A1基因上所有exon區域。 結果：我們在其中的一個家族，檢測出罹患骨關節炎的8 位成員，在COL2A1基因的exon 50全部都有3689G→A transition的情形，另外4未罹患骨關節炎的成員，在COL2A1基因exon 50 的3689G位置上則沒有突變的情形發生。3689G→A這樣的改變會造成胺基酸Gly1170Ser，這個位置是在第二型膠原(Type Ⅱ collagen)的GXY重複區域中。 結論：本研究與國立陽明大學的研究，總共三個家族所發現的突變點，恰巧都是在同一個位置，這可能與「奠基者效應」(Founder effect)有關，可見在台灣的族群當中，有家族性關節問題的家族，有相當的程度是與COL2A1基因的3689G→A有關，因此我們希望以此研究為基礎來建立起家族性早發型骨關節炎與股骨頭缺血性壞死的基因診斷及遺傳諮詢平台，對於有類似情形的病患，我們就可以幫他們做基因的檢測，以及遺傳諮詢，期盼可以藉此來協助罹病家族走出家族魔咒。 | zh_TW |
| dc.description.abstract | Objective: Osteoarthritis (OA) is a very common human joint disease. Currently, we have discovered two families with Familial Early-Onset Osteoarthritis. Looking at the pedigree, one discovers the genetic model conforms to autosomal dominant inheritance of Mendel's Laws of Inheritance. This study aims to build a consultation platform for the genetic diagnosis and inheritance of Taiwan’s Familial Early-Onset Osteoarthritis by investigating whether there is mutation of the COL2A1 gene. If this model can successfully and accurately detect the disease causing gene, patients with similar situation can be given a genetic test and then the appropriate medical intervention and hereditary consultation in the future.
Methods: We have collected the DNA of leukocytes from the 23 members of the two families with Familial Early-Onset Osteoarthritis. The specimens of the subjects are then subjected to PCR and DNA sequencing to analyze the exon region of the COL2A1 gene. Result: In one family, 3689G→A transition is present in exon 50 of the COL2A1 gene in all 8 family members tested to have OA. In the other four family members without OA, 3689G mutation does not exist in exon 50 of the COL2A1 gene. This results in codon change of Gly1170Ser. The location is in the GXY repeat region of Type II collagen. Conclusions: The results of this study and the study done by National Yang Ming University found that the mutation in the three families studied occurred in the same region. This may be related to Founder effect. It is evident that in Taiwan, for families with familial arthritis problems, 3689G→A of the COL2A1 gene is involved to a certain degree. Therefore, we wish to use this study as a foundation to build the genetic diagnosis and hereditary consultation platform for Familial Early-Onset Osteoarthritis and avascular necrosis of the femoral head. Patients with similar situations can then undergo genetic testing and hereditary consultation. Thus, we hope families with history of the disease can bid farewell to the family curse. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T01:04:33Z (GMT). No. of bitstreams: 1 ntu-96-P94448004-1.pdf: 812958 bytes, checksum: fe100640f4c137364ff4b04a452bbd80 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………………… Ⅰ
謝辭…………………………………………………………… Ⅱ 中文摘要……………………………………………………… Ⅲ 英文摘要………………………………………………………. Ⅳ 第一章 緒論…………………………………………………… 1 1.1緣起……………………………………………… 1 1.2 OA臨床表徵……………………………………… 1 1.3 OA分型…………………………………………… 2 1.4 OA病理機轉…………………………………… 2 1.5 OA分子病理機轉……………………………… 5 第二章 研究方法與材料……………………………………… 7 2.1受試者…………………………………………… 7 2.2 基因分析………………………………………... 7 2.2.1 DNA萃取………………………………… 7 2.2.2 PCR……………………………………….. 8 2.2.3 Purification………………………………… 8 2.2.4 Sequencing…………………………………. 10 2.3 結果判讀………………………………………… 10 第三章 結果…………………………………………………… 11 第四章 討論…………………………………………………… 12 參考文獻……………………………………………………… 15 圖表…………………………………………………………… 21 | |
| dc.language.iso | zh-TW | |
| dc.title | 家族性早發型骨關節炎的遺傳診斷與諮詢 | zh_TW |
| dc.title | Familial Early-Onset Osteoarthritis：Genetic Diagnosis and Counseling | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 江清泉,蘇怡寧 | |
| dc.subject.keyword | 骨關節炎,遺傳診斷,第二型膠原, | zh_TW |
| dc.subject.keyword | Osteoarthritis,Genetic Diagnosis,COL2A1, | en |
| dc.relation.page | 43 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-24 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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