Molecular genetic analysis of Down syndrome

Human Genetics

Volumn 126, Issue 1, 2009, Pages 195-214

  Patterson, David ^a  

^a UNIVERSITY OF DENVER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE 3L; MICRORNA; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; CANCER RISK; CHROMOSOME 21; CONGENITAL HEART DISEASE; DISEASE MODEL; DNA METHYLATION; DOWN SYNDROME; EPIGENETICS; GENE EXPRESSION; GENE FUNCTION; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; HIGH RISK POPULATION; HUMAN; INTELLECTUAL IMPAIRMENT; LEUKEMIA; METABOLOMICS; MOLECULAR GENETICS; MOTOR DYSFUNCTION; MUSCLE HYPOTONIA; MUTATIONAL ANALYSIS; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PHENOTYPIC VARIATION; PRIORITY JOURNAL; PROTEIN METHYLATION; PROTEIN PROCESSING; PROTEOMICS; REVIEW; TRANSCRIPTION REGULATION; TRISOMY 21;

ANIMALS; CHROMOSOMES, HUMAN, PAIR 21; DOWN SYNDROME; GENE DOSAGE; GENE EXPRESSION REGULATION; GENETIC VARIATION; HUMANS; MICE; MICE, TRANSGENIC; MICRORNAS; MODELS, ANIMAL; MOSAICISM; PROTEOME; RNA, MESSENGER; TRISOMY;

EID: 67651124806     PISSN: 03406717     EISSN: 14321203     Source Type: Journal    
DOI: 10.1007/s00439-009-0696-8     Document Type: Review

References (154)

1. Ait Yahya-Graison E, Aubert J, Dauphinot AL, Rivals I, Prieur M, Golfier G, Rossier J, Personnaz L, Creau N, Blehaut H, Robin S, Delabar JM, Potier M-C (2007) Classification of human chromosome 21 gene-expression variation in Down syndrome: Impact on disease phenotypes. Am J Hum Genet 81:475-491
2. Altug-Teber O, Bonin M, Walter M, Mau-Holzmann UA, Dufke A, Stappert H, Tekesin I, Heilbronner H, Nieselt K, Riess O (2007) Specific transcriptional changes in human fetuses with autosomal trisomies. Cytogenet Genome Res 119:171-184
3. An S, Kumar R, Sheets ED, Benkovic SJ (2008) Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science 320:103-106
4. Aula P, Leisti J, von Koskull H (1973) Partial trisomy 21. Clin Genet 4:241-251
5. Bai RZ, Wu Y, Liu Q, Xie K, Wei YQ, Wang YS, Liu K, Luo Y, Su JM, Hu B, Liu JY, Li Q, Niu T, Zhao ZW, Yang L (2009) Suppression of lung cancer in murine model: Treated by combination of recombinant human endostsatin adenovirus with low-dose cisplatin. J Exp Clin Cancer Res 28:31
6. Barlow GM, Chen XN, Shi ZY, Lyons GE, Kurnit DM, Celle L, Spinner NB, Zackai E, Pettenati MJ, Van Riper AJ, Vekemans MJ, Mjaatvedt CH, Korenberg JR (2001) Down syndrome congenital heart disease: A narrowed region and a candidate gene. Genet Med 3:91-101
7. Barnes TS, Brodsky GL, Barela GJ, Bleskan JH, Patterson D (1994) Development of a mouse model for the study of human purine metabolism. Adv Exp Med Biol 370:517-521
8. Beacher F, Simmons A, Daly E, Prasher V, Adams C, Margallo-Lana ML, Morris R, Lovestone S, Murphy K, Murphy DG (2005) Hippocampal myo-inositol and cognitive ability in adults with Down syndrome: An in vivo proton magnetic resonance spectroscopy study. Arch Gen Psychiatry 62:1360-1365
9. Belichenko NP, Belichenko PV, Kleschevnikov AM, Salehi A, Reeves RH, Mobley WC (2009) The "Down syndrome critical region" is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome. J Neurosci 29:5938-5948
10. Bercovich D, Ganmore I, Scott LM, Wainreb G, Birger Y, Elimelech A, Shochat C, Cazzaniga G, Biondi A, Basso G, Cario G, Schrappe M, Stanulla M, Strehl S, Haas OA, Mann G, Binder V, Borkhardt A, Kempski H, Trka J, Bielorei B, Avigad S, Stark B, Smith O, Dastugue N, Bourquin JP, Tal NB, Green AR, Izraeli S (2008) Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet 372:1484-1492
11. Berry GT, Mallee JJ, Kwon HM, Rim JS, Mulla WR, Muenke M, Spinner NB (1995) The human osmoregulatory Na+/myo-inositol cotransporter gene (SLC5A3): Molecular cloning and localization to chromosome 21. Genomics 25:507-513
12. Berry GT, Wang ZJ, Dreha SF, Finucane BM, Zimmerman RA (1999) In vivo brain myo-inositol levels in children with Down syndrome. J Pediatr 135:94-97
13. Bock C, Walter J, Paulsen M, Lengauer T (2007) CpG island mapping by epigenome prediction. PLoS Comput Biol 3(6):e110
14. Borg J, Chereul E (2008) Differential MRI patterns of brain atrophy in double or single transgenic mice for APP and/or SOD. J Neurosci Res 86:3275-3284
15. Brodsky G, Barnes T, Bleskan J, Becker L, Cox M, Patterson D (1997) The human GARS-AIRS-GART gene encodes two proteins which are differentially expressed during human brain development and temporally overexpressed in cerebellum of individuals with Down syndrome. Hum Mol Genet 6:2043-2050
16. Buccafusca R, Venditti CP, Kenyon LC, Johanson RA, Van Bockstaele E, Ren J, Pagliardini S, Minarcik J, Golden JA, Coady MJ, Greer JJ, Berry GT (2008) Characterization of the null murine sodium/myo-inositol cotransporter 1 (Smit1 or Slc5a3) phenotype: Myo-inositol rescue is independent of expression of its cognate mitochondrial ribosomal protein subunit 6 (Mrps6) gene and of phosphatidylinositol levels in neonatal brain. Mol Genet Metab 95:81-95
17. Butler C, Knox AJ, Bowersox J, Forbes S, Patterson D (2006) The production of transgenic mice expressing human cystathionine beta-synthase to study Down syndrome. Behav Genet 36:429-438
18. Carmichael CL, Majewski IJ, Alexander WS, Metcalf D, Hilton DJ, Hewitt CA, Scott HS (2009) Hematopoietic defects in the Ts1Cje mouse model of Down syndrome. Blood 113:1929-1937
19. Carson MB, Langlois R, Lu H (2008) Mining knowledge for the methylation status of CpG islands using alternating decision trees. Conf Proc IEEE Eng Med Biol Soc 2008:3787-3790
20. Caspersson T, Hultén M, Lindsten J, Zech L (1970) Distinction between extra G-like chromosomes by quinacrine mustard fluorescence analysis. Exp Cell Res 63:240-243
21. Cataldo AM, Petanceska S, Peterhoff CM, Terio NB, Epstein CJ, Villar A, Carlson EJ, Staufenbiel M, Nixon RA (2003) App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of Down syndrome. J Neurosci 23:6788-6792
22. Centers for Disease Control and Prevention (2006) Improved national prevalence estimates for 18 selected major birth defects - United States, 1999-2001 MMWR 54:1301-1305
23. Chadefaux B, Allard D, Rethoré MO, Raoul O, Poissonnier M, Gilgenkrantz S, Cheruy C, Jérôme H (1984) Assignment of human phosphoribosylglycinamide synthetase locus to region 21q221. Hum Genet 66:190-192
24. Chim SSC, Jin S, Lee TYH, Lun FMF, Lee WS, Chan LYS, Jin Y, Yang N, Ton YK, Leung TY, Lau TK, Ding C, Chiu RWK, Lo YMD (2008) Systemic search for placental DNA-methylation markers on chromosome 21. toward a maternal plasma-based epigenetic test for fetal trisomy 21. Clin Chem 54:500-511
25. Choi JK, Kim Y-J (2009) Intrinsic variability of gene expression encoded in nucleosome positioning sequences. Nat Genet 41:497-503
26. Chou CY, Liu LY, Chen CY, Tsai CH, Hwa HL, Chang LY, Lin YS, Hsieh FJ (2008) Gene expression variation increase in trisomy 21 tissues. Mamm Genome 19:398-405
27. Chrast R, Scott HS, Papasavvas MP, Rossier C, Antonarakis ES, Barras C, Davisson MT, Schmidt C, Estivill X, Dierssen M, Pritchard M, Antonarakis SE (2000) The mouse brain transcriptome by SAGE: Differences in gene expression between P30 brains of the partial trisomy 16 mouse model of Down syndrome (Ts65Dn) and normals. Genome Res 10:2006-2021
28. Ciovacco WA, Raskind WH, Kacena MA (2008) Human phenotypes associated with GATA-1 mutations. Gene 427:1-6
29. Coburn SP, Sirlin EM, Mertz ET (1968) Metabolism of N15 labeled uric acid in Down's syndrome. Metabolism 17:560-562
30. Conti A, Fabbrini F, D'Agostino P, Negri R, Greco D, Genesio R, D'Armiento M, Olla C, Paladini D, Zannini M, Nitsch L (2007) Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy. BMC Genomics 8:268
31. Costa AC, Scott-McKean JJ, Stasko MR (2008) Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test. Neuropsychopharmacology 33:1624-1632
32. Davisson MT, Schmidt C, Akeson EC (1990) Segmental trisomy of murine chromosome 16: A new model system for studying Down syndrome. In: Patterson D, Epstein CJ (eds) Molecular genetics of chromosome 21 and Down syndrome. Wiley, New York, pp 263-280
33. de la Luna S, Estivill X (2006) Cooperation to amplify gene-dosage-imbalance effects. Trends Mol Med 12:451-454
34. Delabar JM, Theophile D, Rahmani Z, Chettouh Z, Blouin JL, Prieur M, Noel B, Sinet PM (1993) Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet 1:114-124
35. Delcuve G, Rastegar M, Davie JR (2009) Epigenetic control. J Cell Physiol 219:243-250
36. Deutsch S, Lyle R, Dermitzakis ET, Attar H, Subrahmanyan L, Gehrig C, Parand L, Gagnebin M, Rougemont J, Jongeneel CV, Antonarakis SE (2005) Gene expression variation and expression quantitative trait mapping of human chromosome 21 genes. Hum Mol Genet 14:3741-3749
37. El-Maarri O, Kareta MS, Mikeska T, Becker T, Diaz-Lacava A, Junen J, Nüsgen N, Behne F, Wienker T, Waha A, Oldenburg J, Chédin F (2009) A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. Hum Mol Genet 18(10):1755-1768
38. Epstein CJ (1981) Animal models for autosomal trisomy. In: De la Cruz FF, Gerald PS (eds) Trisomy 21 (Down syndrome) research perspectives. University Park Press, Baltimore, pp 263-271
39. Fernandez F, Morishita W, Zuniga E, Nguyen J, Blank M, Malenka RC, Garner CC (2007) Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat Neurosci 10:411-413
40. Figaro S, Scrima N, Buckingham RH, Heurgue-Hamard V (2008) HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS Lett 582:2352-2356
41. Friend KK, Chen S, Ruddle FH (1976) Differential staining of interspecific chromosomes in somatic cell hybrids by alkaline Giemsa stain. Somatic Cell Genet 2:183-188
42. Ganesh L, Yoshimoto T, Moorthy NC, Akahata W, Boehm M, Nabel EG, Nabel GJ (2006) Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis. Mol Cell Biol 26:3864-3874
43. Gardiner K (2009) Memory and learning - using mouse to model neurobiological and behavioural aspects of Down syndrome and assess pharmacotherapeutics. Down Syndrome Research and Practice 12, http://www.down-syndrome.org/doi/?10.3104/reviews.2096
44. Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G (2009) MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene re-expression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood [Epub ahead of print]
45. Gearhart JM, Davisson M, Oster-Granite ML (1986) Autosomal aneuploidy in mice: Generation and developmental consequences. Brain Res Bull 16:789-801
46. Gerich FJ, Funke F, Hildebrandt B, Faßhauer M, Müller M (2009) H(2)O(2)-mediated modulation of cytosolic signaling and organelle function in rat hippocampus. Pflugers Arch (in press)
47. Guil S, Esteller M (2009) DNA methylomes, histone codes and miRNAs: tying it all together. Int J Biochem Cell Biol 41:87-95
48. Harris LJW, Swatton JE, Wengenroth M, Wayland M, Lockstone H, Holland A, Faull RLM, Lilley KS, Bahn S (2007) Differences in protein profiles in schizophrenia prefrontal cortex compared to other major brain disorders. Clin Schizophrenia Relat Psychoses 1:73-91
49. Hasle H (2001) Pattern of malignant disorders in individuals with Down's syndrome. Lancet Oncol 2:429-436
50. Hata K, Kusumi M, Yokomine T, Li E, Sasaki H (2006) Meiotic and epigenetic aberrations in Dnmt3L-deficient male germ cells. Mol Reprod Dev 73:116-122
51. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS et al (2000) Chromosome 21 mapping and sequencing consortium. The DNA sequence of human chromosome 21. Nature 405:311-319
52. Helguera P, Pelsman A, Pigino G, Wolvetang E, Head E, Busciglio J (2005) ets-2 promotes the activation of a mitochondrial death pathway in Down's syndrome neurons. J Neurosci 25:2295-2303
53. Henrichsen CN, Vinckenbosch N, Zöllner S, Chaignat E, Pradervand S, Schütz F, Ruedi M, Kaessmann H, Reymond A (2009a) Segmental copy number variation shapes tissue transcriptomes. Nat Genet 41:424-429
54. Henrichsen CN, Chaignat E, Reymond A (2009b) Copy number variants, diseases and gene expression. Hum Mol Genet 18(R1):R1-R8
55. Hermans KG, van Marion R, van Dekken H, Jenster G, van Weerden WM, Trapman J (2006) TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer. Cancer Res 66:10658-10663
56. Hu YG, Hirasawa R, Hu JL, Hata K, Li CL, Jin Y, Chen T, Li E, Rigolet M, Viegas-Péquignot E, Sasaki H, Xu GL (2008) Regulation of DNA methylation activity through Dnmt3L promoter methylation by Dnmt3 enzymes in embryonic development. Hum Mol Genet 17:2654-2664
57. Hunsucker SW, Solomon B, Gawryluk J, Geiger JD, Vacano GN, Duncan MW, Patterson D (2008) Assessment of post-mortem-induced changes to the mouse brain proteome. J Neurochem 105(3):725-737
58. Jenkins EC, Ye L, Gu H, Ni SA, Duncan CJ, Velinov M, Pang D, Krinsky-McHale SJ, Zigman WB, Schupf N, Silverman WP (2008a) Increased "absence" of telomeres may indicate Alzheimer's disease/ dementia status in older individuals with Down syndrome. Neurosci Lett 440:340-343
59. Jenkins EC, Ye L, Gu H, Ni SA, Velinov M, Pang D, Krinsky-McHale SJ, Zigman WB, Schupf N, Silverman WP (2008b) Shorter telomeres may indicate dementia status in older individuals with Down syndrome. Neurobiol Aging [Epub ahead of print]
60. Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, Chen PC (2008) The Nrf2-ARE pathway: An indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 1147:61-69
61. Kaddurah-Daouk R, Krishnan KR (2009) Metabolomics: A global biochemical approach to the study of central nervous system diseases. Neuropsychopharmacology 34:173-186
62. Kaplan N, Moore IK, Fondufe-Mittendorf Y, Gossett AJ, Tillo D, Field Y, LeProust EM, Hughes TR, Lieb JD, Widom J, Segal E (2009) The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458:362-366
63. Keating DJ, Chen C, Pritchard MA (2006) Alzheimer's disease and endocytic dysfunction: Clues from the Down syndrome-related proteins, DSCR1 and ITSN1. Ageing Res Rev 5:388-401
64. Kirsammer G, Jilani S, Liu H, Davis E, Gurbuxani S, Le Beau MM, Crispino JD (2008) Highly penetrant myeloproliferative disease in the Ts65Dn mouse model of Down syndrome. Blood 111:767-775
65. Kitami T, Rubio R, O'Brien W, Quackenbush J, Nadeau JH (2008) Gene-environment interactions reveal a homeostatic role for cholesterol metabolism during dietary folate perturbation in mice. Physiol Genomics 35:182-190
66. Klose J, Zeindl E, Sperling K (1982) Analysis of protein patterns in two-dimensional gels of cultured human cells with trisomy 21. Clin Chem 28:987-992
67. Knox AJ, Graham C, Bleskan J, Brodsky G, Patterson D (2009) Mutations in the Chinese hamster ovary cell GART gene of de novo purine synthesis. Gene 429:23-30
68. Korenberg JR, Kawashima H, Pulst SM, Ikeuchi T, Ogasawara N, Yamamoto K, Schonberg SA, West R, Allen L, Magenis E, Ikawa K, Taniguchi N, Epstein CJ (1990) Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype. Am J Hum Genet 47:236-246
69. Kuhn DE, Nuovo GJ, Martin MM, Malana GE, Pleister AP, Jiang J, Schmittgen TD, Terry AV, Gardiner K, Head E, Feldman DS, Elton TS (2008) Human chromosome 21-derived miRNAs are overexpressed in Down syndrome brains and hearts. Biochem Biophys Res Commun 370:473-477
70. Kwak H-I, Gustafson T, Metz RP, Lafflin B, Schedin P, Porter WW (2007) Inhibition of breast cancer growth and invasion by single-minded 2 s. Carcinogenesis 28:259-266
71. Levine S, Saltzman A, Levy E, Ginsberg SD (2009) Systemic pathology in aged mouse models of Down's syndrome and Alzheimer's disease. Exp Mol Pathol 86:18-22
72. Li CM, Guo M, Salas M, Schupf N, Silverman W, Zigman WB, Husain S, Warburton D, Thaker H, Tycko B (2006) Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21. BMC Med Genet 7:24
73. Li Z, Yu T, Morishima M, Pao A, LaDuca J, Conroy J, Nowak N, Matsui S, Shiraishi I, Yu YE (2007) Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities. Hum Mol Genet 16:1359-1366
74. Liu LL, Smith MJ, Sun BS, Wang GJ, Redmond HP, Wang JH (2009) Combined IFN-gamma-Endostatin Gene Therapy and Radiotherapy Attenuates Primary Breast Tumor Growth and Lung Metastases via Enhanced CTL and NK Cell Activation and Attenuated Tumor Angiogenesis in a Murine Model. Ann Surg Oncol 16:1403-1411
75. Lockrow J, Prakasam A, Huang P, Bimonte-Nelson H, Sambamurti K, Granholm AC (2009) Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model. Exp Neurol 216:278-289
76. Lockstone HE, Harris LW, Swatton JE, Wayland MT, Holland AJ, Bahn S (2007) Gene expression profiling in the adult Down syndrome brain. Genomics 90:647-660
77. Lott IT, Head E (2005) Alzheimer disease and Down syndrome: Factors in pathogenesis. Neurobiol Aging 26:383-389
78. Lott IT, Head E, Doran E, Busciglio J (2006) Beta-amyloid, oxidative stress and down syndrome. Curr Alzheimer Res 3:521-528
79. Lubec G (ed) (2001) Protein expression in Down syndrome brain. Springer, Austria
80. Lyle R, Béna F, Gagos S, Gehrig C, Lopez G, Schinzel A et al (2009) Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. Eur J Hum Genet 17:454-466
81. Majid S, Dar AA, Ahmad A, Hirata H, Kawakami K, Shahryari V, Saini S, Tanaka Y, Dahiya AV, Khatri G, Dahiya R (2009) BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer. Carcinogenesis 30:662-670
82. Marie S, Race V, Nassogne MC, Vincent MF, Van den Berghe G (2002) Mutation of a nuclear respiratory factor 2 binding site in the 5′ untranslated region of the ADSL gene in three patients with adenylosuccinate lyase deficiency. Am J Hum Genet 71:14-21
83. Meyer R, Wolf SS, Obendorf M (2007) PRMT2, a member of the protein arginine methyltransferase family, is a coactivator of the androgen receptor. J Steroid Biochem Mol Biol 107:1-14
84. Minami T, Horiuchi K, Miura M, Abid MR, Takabe W, Noguchi N, Kohro T, Ge X, Aburatani H, Hamakubo T, Kodama T, Aird WC (2004) Vascular endothelial growth factor- and thrombin-induced termination factor, Down syndrome critical region-1, attenuates endothelial cell proliferation and angiogenesis. J Biol Chem 279:50537-50554
85. Miyabara S, Gropp A, Winking H (1982) Trisomy 16 in the mouse fetus associated with generalized edema and cardiovascular and urinary tract anomalies. Teratology 25:369-380
86. Mural RJ, Adams MD, Myers EW, Smith HO, Miklos GL, Wides R et al (2002) A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome. Science 296:1661-1671
87. Ni ZL, Zhao SP, Wu Z (2007) ABCG1 - a potential therapeutic target for atherosclerosis. Med Hypotheses 69:214-217
88. Niebuhr E (1974) Down's syndrome: The possibility of a pathogenetic segment on chromosome. Humangenetik 21:99-101
89. O'Doherty A, Ruf S, Mulligan C, Hildreth V, Errington ML, Cooke S, Sesay A, Modino S, Vanes L, Hernandez D, Linehan JM, Sharpe PT, Brandner S, Bliss TV, Henderson DJ, Nizetic D, Tybulewicz VL, Fisher EM (2005) An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309:2033-2037
90. Ohgaki K, Iida A, Kasumi F, Sakamoto G, Akimoto M, Nakamura Y, Emi M (1998) Mapping of a new target region of allelic loss to a 6-cM interval at 21q21 in primary breast cancers. Genes Chromosomes Cancer 23:244-247
91. Olson LE, Richtsmeier JT, Leszl J, Reeves RH (2004) A chromosome 21 critical region does not cause specific Down syndrome phenotypes. Science 306:687-690
92. Olson LE, Roper RJ, Sengstaken CL, Peterson EA, Aquino V, Galdzicki Z, Siarey R, Pletnikov M, Moran TH, Reeves RH (2007) Trisomy for the Down syndrome "critical region" is necessary but not sufficient for brain phenotypes of trisomic mice. Hum Mol Genet 16:774-782
93. Ooi SKT, Qiu C, Bernstein E, Li K, Jia D, Yang Z, Erdjument-Bromage H, Tempst P, Lin S-P, Allis CD, Cheng X, Bestor TH (2007) DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448:714-717
94. Ou YH, Chung PH, Hsu FF, Sun TP, Chang WY, Shieh SY (2007) The candidate tumor suppressor BTG3 is a transcriptional target of p53 that inhibits E2F1. EMBO J 26:3968-3980
95. Pant SS, Moser HW, Krane SM (1968) Hyperuricemia in Down's syndrome. J Clin Endocrinol Metab 28:472-478
96. Park J, Oh Y, Chung KC (2009) Two key genes closely implicated with the neuropathological characteristics in Down syndrome: DYRK1A and RCAN1. BMB Rep 42:6-15
97. Patterson D (2007) Genetic mechanisms involved in the phenotype of Down syndrome. Ment Retard Dev Disabil Res Rev 13:199-206
98. Patterson D (2008) Folate metabolism and the risk of Down syndrome. Downs Syndr Res Pract 12:93-97
99. Patterson D, Costa ACS (2005) Down syndrome and genetics - a case of linked histories. Nat Rev Genet 6:137-147
100. Patterson D, Jones C, Scoggin C, Miller YE, Graw S (1982) Somatic cell genetic approaches to Down's syndrome. Ann N Y Acad Sci 396:69-381
101. Patterson D, Graham C, Cherian C, Matherly LH (2008) A humanized mouse model for the reduced folate carrier. Mol Genet Metab 93:95-103
102. Paz-Miguel JE, Flores R, Sánchez-Velasco P, Ocejo-Vinyals G, Escribano de Diego J, López de Rego J, Leyva-Cobián F (1999) Reactive oxygen intermediates during programmed cell death induced in the thymus of the Ts(1716)65Dn mouse, a murine model for human Down's syndrome. J Immunol 163:5399-5410
103. Polani E, Adinolfi M (1980) Chromosome 21 of man, 22 of the great apes and 16 of the mouse. Dev Med Child Neurol 22:223-233
104. Prandini P, Deutsch S, Lyle R, Gagnebin M, Delucinge Vivier C, Delorenzi M, Gehrig C, Descombes P, Sherman S, Dagna Bricarelli F, Baldo C, Novelli A, Dallapiccola B, Antonarakis SE (2007) Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance. Am J Hum Genet 81:252-263
105. Prasher VP, Farrer MJ, Kessling AM, Fisher EM, West RJ, Barber PC, Butler AC (1998) Molecular mapping of Alzheimer-type dementia in Down's syndrome. Ann Neurol 43:380-383
106. Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu Y-J (2002) Identification of protein arginine methyltransferase 2 as a coactivator of estrogen receptor alpha. J Biol Chem 277:28624-28630
107. Rachidi M, Lopes C (2008) Mental retardation and associated neurological dysfunctions in Down syndrome: A consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways. Eur J Paediatr Neurol 12:168-182
108. Rahmani Z (2006) APRO4 negatively regulates Src tyrosine kinase activity in PC12 cells. J Cell Sci 119:646-658
109. Ratel D, Ravanat JL, Charles MP, Platet N, Breuillaud L, Lunardi J, Berger F, Wion D (2006) Undetectable levels of N6-methyl adenine in mouse DNA: Cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase. FEBS Lett 580:3179-3184
110. Roizen NJ (2005) Complementary and alternative therapies for Down syndrome. Ment Retard Dev Disabil Res Rev 11:149-155
111. Roizen NJ, Patterson D (2003) Down's syndrome. Lancet 361:1281-1289
112. Rosa-Rosa JM, Pita G, Urioste M, Llort G, Brunet J, Lázaro C, Blanco I, Ramón y Cajal T, Díez O, de la Hoya M, Caldés T, Tejada MI, González-Neira A, Benítez J (2009) Genome-wide linkage scan reveals three putative breast-cancer-susceptibility loci. Am J Hum Genet 84:115-122
113. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerrière A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T, Campion D (2006) APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38:24-26
114. Rueda N, Flórez J, Martínez-Cué C (2008) Chronic pentylenetetrazole but not donepezil treatment rescues spatial cognition in Ts65Dn mice, a model for Down syndrome. Neurosci Lett 433:22-27
115. Ryeom S, Baek K-H, Rioth MJ, Lynch RC, Zaslavsky A, Birsner A, Yoon SS, McKeon F (2008) Targeted deletion of the calcineurin inhibitor DSCR1 suppresses tumor growth. Cancer Cell 13:420-431
116. Sago H, Carlson EJ, Smith DJ, Kilbridge J, Rubin EM, Mobley WC, Epstein CJ, Huang TT (1998) Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proc Natl Acad Sci USA 95:6256-6261
117. Salman M (2002) Systematic review of the effect of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome. Eur J Paediatr Neurol 6:213-219
118. Satgé D, Sommelet D, Geneix A, Nishi M, Malet P, Vekemans M (1998) A tumor profile in Down syndrome. Am J Med Genet 78:207-216
119. Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS, Hatzigeorgiou AG, Antonarakis SE (2007) Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3′ untranslated region: A mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet 81:405-413
120. Shapiro BL (1983) Down syndrome - a disruption of homeostasis. Am J Med Genet 14:241-269
121. Shetty HU, Siarey RJ, Galdzicki Z, Stoll J, Rapoport SI (2000) Ts65Dn mouse, a Down syndrome model, exhibits elevated myo-inositol in selected brain regions and peripheral tissues. Neurochem Res 25:431-435
122. Shimizu R, Engel JD, Yamamoto M (2008) GATA 1-related leukemias. Nat Rev Cancer 8:279-286
123. Shovlin TC, Bourc'his D, La Salle S, Doherty AO, Trasler JM, Bestor TH, Walsh CP (2007) Sex-specific promoters regulate Dnmt3L expression in mouse germ cells. Hum Reprod 22:457-467
124. Siddiqui A, Lacroix T, Stasko MR, Scott-McKean JJ, Costa AC, Gardiner KJ (2008) Molecular responses of the Ts65Dn and Ts1Cje mouse models of Down syndrome to MK-801. Genes Brain Behav 7:810-820
125. Sleegers K, Brouwers N, Gijselinck I, Theuns J, Goossens D, Wauters J, Del-Favero J, Cruts M, van Duijn CM, Van Broeckhoven C (2006) APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy. Brain 129:2977-2983
126. Sommer CA, Pavarino-Bertelli EC, Goloni-Bertollo EM, Henrique-Silva F (2008) Identification of dysregulated genes in lymphocytes from children with Down syndrome. Genome 51:19-29
127. Spiegel EK, Colman RF, Patterson D (2006) Adenylosuccinate lyase deficiency. Mol Genet Metab 89:19-31
128. Squire JA (2009) TMPRSS2-ERG and PTEN loss in prostate cancer. Nat Genet 41:509
129. Stankiewicz MJ, Crispino JD (2009) ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells. Blood 113:1347-3337
130. Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N, Redon R, Bird CP, de Grassi A, Lee C, Tyler-Smith C, Carter N, Scherer SW, Tavaré S, Deloukas P, Hurles ME, Dermitzakis ET (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315:848-853
131. Sultan M, Piccini I, Balzereit D, Herwig R, Saran NG, Lehrach H, Reeves RH, Yaspo ML (2007) Gene expression variation in Down's syndrome mice allows prioritization of candidate genes. Genome Biol 8:R91
132. Min-mediated tumors in mouse models of Down syndrome. Nature 451:73-76
133. Takashima S, Takehashi M, Lee J, Chuma S, Okano M, Hata K, Suetake I, Nakatsuji N, Miyoshi H, Tajima S, Tanaka Y, Toyokuni S, Sasaki H, Kanatsu-Shinohara M, Shinohara T (2009) Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenic defects. Biol Reprod [Epub ahead of print]
134. The ENCODE Project Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816
135. Tunstall-Pedoe O, Roy A, Karadimitris A, de la Fuente J, Fisk NM, Bennett P, Norton A, Vyas P, Roberts I (2008) Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations. Blood 112:4507-4511
136. Unlü M, Morgan ME, Minden JS (1997) Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 18:2071-2077
137. Vacík T, Ort M, Gregorová S, Strnad P, Blatny R, Conte N, Bradley A, Bures J, Forejt J (2007) Segmental trisomy of chromosome 17: a mouse model of human aneuploidy syndromes. Proc Natl Acad Sci USA 102:4500-4505
138. Van Keuren ML, Goldman D, Merril CR (1982) Protein variations associated with Down's syndrome, chromosome 21, and Alzheimer's disease. Ann N Y Acad Sci 396:55-67
139. Voronov SV, Frere SG, Giovedi S, Pollina EA, Borel C, Zhang H, Schmidt C, Akeson EC, Wenk MR, Cimasoni L, Arancio O, Davisson MT, Antonarakis SE, Gardiner K, De Camilli P, Di Paolo G (2008) Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome. Proc Natl Acad Sci USA 105:9415-9420
140. Vyas P, Crispino JD (2007) Molecular insights into Down syndrome-associated leukemia. Curr Opin Pediatr 19:9-14
141. Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: A revolutionary tool for transcriptomics. Nat Rev Genet 10:57-63
142. Weil J, Epstein CJ (1979) The effect of trisomy 21 on the patterns of polypeptide synthesis in human fibroblasts. Am J Hum Genet 31:478-488
143. Williams AD, Mjaatvedt CH, Moore CS (2008) Characterization of the cardiac phenotype in neonatal Ts65Dn mice. Dev Dyn 237:426-435
144. Wilson MD, Barbosa-Morais NL, Schmidt D, Conboy CM, Vanes L, Tybulewicz VLJ, Fisher EMC, Tavare S, Odom DT (2008) Species-specific transcription in mice carrying human chromosome 21. Science 322:434-438
145. Wisniewski KE, Kida E, Golabek AA, Walus M, Rabe A, Palminiello S, Albertini G (2006) Down syndrome: From pathology to pathogenesis. In: Rondal JA, Perera J (eds) Down syndrome. Neurobehavioural Specificity. Wiley, Chichester, pp 17-33
146. Wu X, Wakamiya M, Vaishnav S, Geske R, Montgomery C Jr, Jones P, Bradley A, Caskey CT (1994) Hyperuricemia and urate nephropathy in urate oxidase-deficient mice. Proc Natl Acad Sci USA 91:742-746
147. Yamada Y, Watanabe H, Miura F, Soejima H, Uchiyama M, Iwasaka T, Mukai T, Sakaki Y, Ito S (2004) A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q. Genome Res 14:247-266
148. Yang Q, Rasmussen SA, Friedman JM (2002) Mortality associated with Down's syndrome in the USA from 1983 to 1997: A population-based study. Lancet 359:1019-1025
149. Yoshimoto T, Boehm M, Olive M, Crook MF, San H, Langenickel T, Nabel EG (2006) The arginine methyltransferase PRMT2 binds RB and regulates E2F function. Exp Cell Res 312:2040-2053
150. Yu J, Zhang Y, Qi Z, Kurtycz D, Vacano G, Patterson D (2008) Methylation-mediated downregulation of the B-cell translocation gene 3 (BTG3) in breast cancer cells. Gene Expr 14:173-182
151. Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797-801
152. Zeisel SH (2009) Epigenetic mechanisms for nutrition determinants of later health outcomes. Am J Clin Nutr 89:1488S-1493S
153. Zhang Y, Qu ZH, Cui M, Guo C, Zhang XM, Ma CH, Sun WS (2009) Combined endostatin and TRAIL gene transfer suppresses human hepatocellular carcinoma growth and angiogenesis in nude mice. Cancer Biol Ther 8(5) [Epub ahead of print]
154. Zitnanová I, Korytár P, Aruoma OI, Sustrová M, Garaiová I, Muchová J, Kalnovicová T, Pueschel S, Duracková Z (2004) Uric acid and allantoin levels in Down syndrome: Antioxidant and oxidative stress mechanisms? Clin Chim Acta 341:14-139