侯懿婷。退化性神經疾病：PPP2R2B 基因族群遺傳分析及分生研究。
國立台灣師範大學生命科學系九十三學年度碩士論文。2005。
劉若芸。PPP2R2B 基因遺傳檢測、啟動子記述與單一鹼基多型性分 析。國立台灣師範大學生命科學系九十五學年度碩士論文。2007。
Al-Mahdawi S, Pinto RM, Ismail O, Varshney D, Lymperi S, Sandi C, Trabzuni D, Pook M. The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. Hum Mol Genet 2008; 17:
735-746.
Anderson JP, Esch FS, Keim PS, Sambamurti K, Lieberburg I, Robakis NK. Exact cleavage site of Alzheimer amyloid precursor in neuronal PC-12 cells.Neurosci Lett 1991; 128: 126-128.
Artiga MJ, Bullido MJ, Sastre I, Recuero M, García MA, Aldudo J, Vázquez J, Valdivieso F. Allelic polymorphisms in the transcriptional regulatory region of apolipoprotein E gene. FEBS Lett 1998a; 421:
105-108.
Artiga MJ, Bullido MJ, Frank A, Sastre I, Recuero M, García MA, Lendon CL, Han SW, Morris JC, Vázquez J, Goate A, Valdivieso F.
Risk for Alzheimer's disease correlates with transcriptional activity of the APOE gene. Hum Mol Genet 1998b; 7: 1887-1892.
Bird A. DNA methylation patterns and epigenetic memory. Genes Dev
Brusco A, Cagnoli C, Franco A, Dragone E, Nardacchione A, Grosso E, Mortara P, Mutani R, Migone N, Orsi L. Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions. J Neurol 2002; 249: 923-929.
Capell A, Saffrich R, Olivo JC, Meyn L, Walter J, Grunberg J, Mathews P, Nixon R, Dotti C, Haass C. Cellular expression and proteolytic processing of presenilin proteins is developmentally regulated during neuronal differentiation. J Neurochem 1997; 69: 2432-2440.
Cedar H. DNA methylation and gene activity. Cell 1988; 53: 3-4.
Chen CM, Hou YT, Liu JY, Wu YR, Lin CH, Fung HC, Hsu WC, Hsu Y, Lee SH, Hsieh-Li HM, Su MT, Chen ST, Lane HY, Lee-Chen GJ.
PPP2R2B CAG repeat length in the Han Chinese in Taiwan:
Association analyses in neurological and psychiatric disorders and potential functional implications. Am J Med Genet B Neuropsychiatr Genet 2008. [Epub ahead of print]
Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications. Cell 2000; 103: 263-271.
Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921-923.
Cummings JL. Vascular subcortical dementias: clinical aspects. Dementia 1994; 5: 177-180.
Dagda RK, Zaucha JA, Wadzinski BE, Strack S. A developmentally regulated, neuron-specific splice variant of the variable subunit
Bbeta targets protein phosphatase 2A to mitochondria and modulates apoptosis. J Biol Chem 2003; 278: 24976-24985.
Desmond DW. Vascular dementia: a construct in evolution. Cerebrovasc Brain Metab Rev 1996; 8: 296-325.
Dowjat WK, Wisniewski T, Efthimiopoulos S, Wisniewski HM.
Inhibition of neurite outgrowth by familial Alzheimer's disease-linked presenilin-1 mutations. Neurosci Lett 1999; 267:
141-144.
Ferrer I, Blanco R, Carmona M. Differential expression of active, phosphorylation-dependent MAP kinases, MAPK ⁄ ERK, SAPK ⁄ JNK and p38, and specific transcription factor substrates following quinolinic acid excitotoxicity in the rat. Brain Res Mol Brain Res 2001; 94: 48-58.
Fujigasaki H, Verma IC, Camuzat A, Margolis RL, Zander C, Lebre AS, Jamot L, Saxena R, Anand I, Holmes SE, Ross CA, Dürr A, Brice A.
SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family. Ann Neurol 2001; 49: 117-121.
Fuso A, Seminara L, Cavallaro RA, D'Anselmi F, Scarpa S.
S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 2005; 1: 195-204.
Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991; 349: 704-706.
Goedert, M. Tau protein and the neurofibrillary pathology of Alzheimer's disease. Trends Neurosci 1993; 16: 460-465.
Gong CX, Shaikh S, Wang JZ, Zaidi T, Grundke-Iqbal I, Iqbal K.
Phosphatase activity toward abnormally phosphorylated tau:
decrease in Alzheimer disease brain. J Neurochem 1995; 65:
732-738.
Gong CX, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K.
Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease. J Biol Chem 2000; 275: 5535-5544.
Gotz, J. Tau and transgenic animal models. Brain Res Rev 2001; 35:
266-286.
Greene E, Mahishi L, Entezam A, Kumari D, Usdin K. Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res 2007; 35:
3383-3390.
Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 1986a; 261: 6084-6089.
Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule associated protein τ in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci 1986b; 83:
4913-4917.
Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, Lieberburg I, Koo EH, Schenk D, Teplow DB.
Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 1992; 359: 322-325.
Healy AM, Zolnierowicz S, Stapleton AE, Goebl M, DePaoli-Roach AA, Pringle J R. CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2A protein phosphatase. Mol Cell Biol 1991; 11: 5767-5780.
Holmes SE, O'Hearn EE, McInnis MG, Gorelick-Feldman DA, Kleiderlein JJ, Callahan C, Kwak NG, Ingersoll-Ashworth RG, Sherr M, Sumner AJ, Sharp AH, Ananth U, Seltzer WK, Boss MA, Vieria-Saecker AM, Epplen JT, Riess O, Ross CA, Margolis RL.
Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12. Nat Genet 1999; 23: 391-392.
Holmes SE, O'Hearn E, Margolis RL. Why is SCA12 different from other SCAs? Cytogenet Genome Res 2003; 100: 189-197.
Iqbal K, Grundke-Iqbal, I, Smith AJ, George L, Tung YC, Zaidi T.
Identification and localization of a tau peptide to paired helical filaments of Alzheimer disease. Proc Natl Acad Sci 1989; 86:
5646-5650.
Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y.
Visualization of Aβ42(43) and Aβ40 in senile plaques with end specific Aβ monoclonals: evidence that an initially deposited species is Aβ42(43). Neuron 1994; 13: 45-53.
Janssens V, Goris J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and
Jicha GA, Weaver C, Lane E, Vianna C, Kress Y, Rockwood J, Davies P.
cAMP-dependent protein kinase phosphorylations on tau in Alzheimer's disease. J Neurosci 1999; 19: 7486-7494.
Kim Y, Nam YJ, Lee C. Analysis of the SREBF2 gene as a genetic risk factor for vascular dementia. Am J Med Genet B Neuropsychiatr Genet 2005; 139: 19-22.
Kim Y, Kim JH, Nam YJ, Kim YJ, Yu KH, Lee BC, Lee C. Sequence variants of ACE, AGT, AT1R, and PAI-1 as genetic risk factors for vascular dementia. Neurosci Lett 2006; 401: 276-279.
Kim Y, Lee C. The gene encoding transforming growth factor beta 1 confers risk of ischemic stroke and vascular dementia. Stroke 2006;
37: 2843-2845.
Laurent C, Niehaus D, Bauché S, Levinson DF, Soubigou S, Pimstone S, Hayden M, Mbanga I, Emsley R, Deleuze JF, Mallet J. CAG repeat polymorphisms in KCNN3 (HSKCa3) and PPP2R2B show no association or linkage to schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2003; 116: 45-50.
Lee VM, Balin BJ, Otvos Jr L, Trojanowski JQ. A68: a major subunit of paired helical filaments and derivatized forms of normal Tau.
Science 1991; 251: 675-678.
Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 1995;
269: 973-977.
Liu F, Grundke-Iqbal I, Iqbal K, Gong CX. Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau
phosphorylation. Eur J Neurosci 2005; 22: 1942-1950.
Looi JC, Sachdev PS. Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999; 53: 670-678.
Lv H, Jia L, Jia J. Promoter polymorphisms which modulate APP expression may increase susceptibility to Alzheimer's disease.
Neurobiol Aging 2008; 29: 194-202.
Majounie E, Wardle M, Muzaimi M, Cross WC, Robertson NP, Williams NM, Morris HR. Case control analysis of repeat expansion size in ataxia. Neurosci Lett 2007; 429: 28-32.
Mani ST, Thakur MK. In the cerebral cortex of female and male mice, amyloid precursor protein (APP) promoter methylation is higher in females and differentially regulated by sex steroids. Brain Res 2006;
1067: 43-47.
Mayer RE, Hendrix P, Cron P, Matthies R, Stone SR, Goris J, Merlevede W, Hofsteenge J, Hemmings BA. Structure of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence for a neuronal-specific isoform. Biochemistry 1991; 30: 3589-3597.
Mori S, Cao Y, Sogawa K, Kondo K, Sakai T, Hino N, Yamashiro H, Okada M, Miyamoto K, Kawaguchi Y, Mashiba T, Norimatsu H.
Enhanced expression of protein phosphatase 2A associated with hyper-phosphorylation of histone H1 in Alzheimer's disease brain.
Res Commun Mol Pathol Pharmacol 2003; 113-114: 67-73.
Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, Lannfelt L. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet 1992;
Namba Y, Tomonaga M, Kawasaki H, Otomo E, Ikeda K. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt–Jakob disease. Brain Res 1991; 541: 163-166.
Nyholt DR. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 2004; 74: 765-769.
Pei JJ, Tanaka T, Tung YC, Braak E, Iqbal K, Grundke-Iqbal I.
Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain. J Neuropathol Exp Neurol 1997; 56:
70-78.
Pei JJ, Grundke-Iqbal I, Iqbal K, Bogdanovic N, Winblad B, Cowburn RF.
Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration.
Brain Res 1998; 797: 267-277.
Pei JJ, Braak E, Braak H, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Distribution of active glycogen synthase kinase 3 beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes. J Neuropathol Exp Neurol 1999; 58: 1010-1019.
Pietrobono R, Tabolacci E, Zalfa F, Zito I, Terracciano A, Moscato U, Bagni C, Oostra B, Chiurazzi P, Neri G. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 2005; 14: 267-277.
Price NE, Mumby MC. Brain protein serine/threonine phosphatases.
Curr Opin Neurobiol 1999; 9: 336-342.
Ringman JM, Rao PN, Lu PH, Cederbaum S. Mosaicism for trisomy 21
in a patient with young-onset dementia: a case report and brief literature review. Arch Neurol 2008; 65: 412-415.
Santoro MF, Annand RR, Robertson MM, Peng YW, Brady MJ, Mankovich JA, Hackett MC, Ghayur T, Walter G, Wong WW, Giegel DA. Regulation of protein phosphatase 2A activity by caspase-3 during apoptosis. J Biol Chem 1998; 273: 13119-13128.
Scarpa S, Fuso A, D'Anselmi F, Cavallaro RA. Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease? FEBS Lett 2003; 541: 145-148.
Scarpa S, Cavallaro RA, D'Anselmi F, Fuso A. Gene silencing through methylation: an epigenetic intervention on Alzheimer disease. J Alzheimers Dis 2006; 9: 407-414.
Schellenberg GD, Bird TD, Wijsman EM, Orr HT, Anderson L, Nemens E, White JA, Bonnycastle L, Weber JL, Alonso ME. Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14.
Science 1992; 258: 668-671.
Schild A, Schmidt K, Lim YA, Ke Y, Ittner LM, Hemmings BA, Götz J.
Altered levels of PP2A regulatory B/PR55 isoforms indicate role in neuronal differentiation. Int J Dev Neurosci 2006; 24: 437-443.
Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids.Nature 1992; 359: 325-327.
Shiomi K, Takeichi M, Nishida Y, Nishi Y, Uemura T. Alternative cell fate choice induced by low-level expression of a regulator of protein
phosphatase 2A in the Drosophila peripheral nervous system.
Development 1994; 120: 1591-1599.
Silva PN, Gigek CO, Leal MF, Bertolucci PH, de Labio RW, Payão SL, Smith Mde A. Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer's disease. J Alzheimers Dis 2008; 13: 173-176.
Sontag E, Nunbhakdi-Craig V, Lee G, Bloom GS, Mumby MC.
Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Neuron 1996; 17:
1201-1207.
Srivastava AK, Choudhry S, Gopinath MS, Roy S, Tripathi M, Brahmachari SK, Jain S. Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12. Ann Neurol 2001; 50:
796-800.
Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68: 978-989.
Strack S, Zaucha JA, Ebner FF, Colbran RJ, Wadzinski BE. Brain protein phosphatase 2A: developmental regulation and distinct cellular and subcellular localization by B subunits. J Comp Neurol 1998; 392:
515-527.
Sulkava R, Kainulainen K, Verkkoniemi A, Niinisto L, Sobel E, Davanipour Z, Polvikoski T, Haltia M, Kontula K. APOE alleles in Alzheimer's disease and vascular dementia in a population aged 85+.
Neurobiol Aging 1996; 17: 373-376.
Sulek A, Hoffman-Zacharska D, Bednarska-Makaruk M, Szirkowiec W,
Zaremba J. Polymorphism of trinucleotide repeats in non-translated regions of SCA8 and SCA12 genes: allele distribution in a Polish control group. J Appl Genet 2004; 45: 101-105.
Takai D, Jones PA. The CpG island searcher: a new WWW resource. In Silico Biol 2003;3:235-240.
Tsai HF, Liu CS, Leu TM, Wen FC, Lin SJ, Liu CC, Yang DK, Li C, Hsieh M. Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan.
Acta Neurol Scand 2004; 109: 355-360.
Turowski P, Myles T, Hemmings BA, Fernandez A, Lamb NJ. Vimentin dephosphorylation by protein phosphatase 2A is modulated by the targeting subunit B55. Mol Biol Cell 1999; 10: 1997-2015.
Virshup DM. Protein phosphatase 2A: a panoply of enzymes. Curr Opin Cell Biol 2000; 12: 180-185.
Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc Natl Acad Sci 1975;72: 1858-1862.
Wu J, Basha MR, Zawia NH. The environment, epigenetics and amyloidogenesis. J Mol Neurosci 2008; 34: 1-7.
Xiao J, Perry G, Troncoso J, Monteiro MJ. Alpha-calcium-calmodulin -dependent kinase II is associated with paired helical filaments of Alzheimer's disease. J Neuropathol Exp Neurol 1996; 55: 954-963.
Yamaguchi H, Ishiguro K, Uchida T, Takashima A, Lemere CA, Imahori K. Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK) I ⁄ glycogen synthase kinase-3
Neuropathol (Berl) 1996; 92: 232-241.
Yan C, Boyd DD. Histone H3 acetylation and H3 K4 methylation define distinct chromatin regions permissive for transgene expression. Mol Cell Biol 2006; 26: 6357-6371.
圖一、PPP2R2B 基因的結構與其所表現的轉錄體和蛋白質。外顯子 (exon) 1.1 或 1.2 的啟動子差異使用及選擇性裁接，產生 N 端相異 的 Bβ1 及 Bβ2 兩種異構型。外顯子 1.1 上具有 CAG 三核甘酸重 複 (CAG)n (圖片出自 Dagda et al., 2003)
圖二、Bβ1 (A)、Bβ2 (B) 啟動子及 5' 端外顯子區域的 CpG 島預測
分 析 (http://cpgislands.usc.edu/cpg.aspx) 。 彎 曲 箭 頭 +1 標 示 處 為 Bβ1、Bβ2 的轉錄起始位置，標示 ATG 處為外顯子 1.1、1.2 轉譯 的起始點。藍色長方形標示處為 CpG 島，Bβ1 啟動子及 5' 端外顯 子區域具有兩個 CpG 島，Bβ2 啟動子及 5' 端外顯子區域則無 CpG 島的存在。
圖三、白血球 DNA 的 Bβ1 5' 端區域的 RE-PCR 甲基化檢測分 析。(A) 正常人 (NC) 與阿茲海默氏症患者 (AD) 白血球的基因組 DNA 分別經過未添加酵素 ( - )、添加甲基化敏感酵素 HpaII ( H )、
添加甲基化不敏感酵素 MspI ( M ) 處理的 0.8% 瓊脂膠體電泳分析
圖 。(B) 以上述處理後基因組 DNA 為模板之 PCR 產物 (Bβ1 5'UTR 區域，+111 ~ +468, 358 bp) 的 1.4% 瓊脂膠體電泳分析圖，
PCR 增幅 Bβ1 遠端啟動子片段 (-1974 ~ -1824, 151 bp) 作為內在 對照組。(C) 20 位正常人與 20 位阿茲海默氏症患者之甲基化程度的 分佈圖。(D) 上述正常人與阿茲海默氏症患之甲基化程度量化圖。
圖四、淋巴細胞株 DNA 的 Bβ1 5' 端區域的 RE-PCR 甲基化檢測
分析。(A) 正常人 (NC) 與阿茲海默氏症患者 (AD) 淋巴細胞株的基 因組 DNA 分別經過未添加酵素 ( - )、添加甲基化敏感酵素 HpaII ( H )、添加甲基化不敏感酵素 MspI ( M ) 處理的 0.8% 瓊脂膠體電泳 分析圖。(B) 以上述處理後基因組 DNA 為模板之 PCR 產物 (Bβ1 5'UTR 區域，+111 ~ +468, 358 bp) 的 1.4% 瓊脂膠體電泳分析圖，
PCR 增幅 Bβ1 遠端啟動子片段 (-1974 ~ -1824, 151 bp) 作為內在 對照組。(C) 6 組年齡與性別配對的正常人 (N1~N6)、阿茲海默氏症 患者 (P1~P6) 淋巴細胞株之甲基化程度的分佈圖。(D) 上述配對的 6 組正常人與阿茲海默氏症患者淋巴細胞株之甲基化程度量化圖。
圖五、N5 正常人淋巴細胞株 DNA 的 Bβ1 5' 端區域的 Bisulfite sequencing 甲基化檢測分析。(A) ~ (E) 為包含 Bβ1 5'UTR RE-PCR 甲基化檢測區域 (+49 ~ +543, 495 bp) 序列中的部分 CpG 島，TG 代表未被甲基化的 CpG，TTGG 為 RE-PCR 技術中酵素 HpaII 與 MspI 所辨認的位置。TG 下方數字 (1 ~ 8) 為圖七比較的 8 個CpG 位置。
圖六、P3 阿茲海默氏症患者淋巴細胞株 DNA 的 Bβ1 5' 端區域的 Bisulfite sequencing 甲基化檢測分析。(A) ~ (E) 為包含 Bβ1 5'UTR RE-PCR甲基化檢測區域 (+49 ~ +543, 495 bp) 序列中的部分 CpG
島，TG 代表未被甲基化的 CpG，CG 代表甲基化的 CpG，TTGG 為 RE-PCR 技術中酵素 HpaII 與 MspI 所辨認的位置。TG 或 CG 下 方數字 (1 ~ 8) 為圖七比較的 8 個CpG 位置。
圖七、6 組配對的阿茲海默氏症患 (P1 ~ P6) 與正常人 (N1 ~ N6) 淋 巴細胞株之甲基化 (M) 程度量化圖。上方數字 (1 ~ 8) 表示圖五、
圖六中標示的 CpG 位置。全黑的圓圈代表 100% 的甲基化；3/4 黑 的圓圈代表 75% 的甲基化；1/2 黑的圓圈代表 50% 的甲基化；1/4 黑的圓圈代表 25% 的甲基化，全白的圓圈代表 0% 的甲基化。
圖八、淋巴細胞株 DNA 的 CHIP-PCR 檢測。(A) (D) 基因組 DNA 經超音波震盪前 ( - )、後 ( + ) 的 0.8% 瓊脂膠體電泳圖。以抗體 anti-dimethyl H3-K9 (B) 或 anti-acetyl H3-K14 (E) 進行 CHIP-PCR 後產物的 0.8% 瓊脂膠體電泳圖，lane P 未經 CHIP 步驟，lane - 未 加抗體、但經 CHIP 步驟，lane + 加抗體、且經 CHIP 步驟，PCR 產物大小為 358 bp Bβ1 (+111 ~ +468)、301 bp Bβ2 (-193 ~ +108)，+1 為轉錄起始位置。配對的 3 組阿茲海默氏症患與正常人 (P2/N2、
P4/N4、P5/N5) Bβ1、Bβ2 5' 端區域組蛋白修飾的相對量化圖。
圖九、Real time RT-PCR 檢測淋巴細胞株中 PPP2R2B (A)、HPRT (B) mRNA 的表現量。
圖十、Bβ1 基因遠端啟動子多型性的定序圖。(A) -4329 G/A 多型性 的異型合子。(B) -3177 C/T 多型性的異型合子。(C) -2930 A/G 多型 性的異型合子。(D) -2737 G/A 多型性的異型合子。(E) -1918 T/A 多 型性的同型合子。(F) -437 A/G 多型性的同型合子。
圖十一、Bβ1 啟動子多型性檢測。(A) -4329 G/A 多型性。GG、GA、
AA 各基因型的 DNA 樣品經增幅後的 BciVI (GTATCC) 切割、
2.0% 洋菜膠體電泳照片。(B) -3177 C/T 多型性。CC、CT、TT 各基 因型的 DNA 樣品經增幅後的 BsmAI (GTCTC) 切割、2.0% 洋菜膠 體電泳照片。(C) -2930 A/G 多型性。AA、AG、GG 各基因型的 DNA 樣品經增幅後的 SphI (GCATGC) 切割、1.4% 洋菜膠體電泳照片。
(D) -2737 G/A多型性。GG、GA、AA各基因型的 DNA 樣品經增幅
(D) -2737 G/A多型性。GG、GA、AA各基因型的 DNA 樣品經增幅