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Bertolin, Cinzia (2008) Caratterizzazione genetico-molecolare di un campione di soggetti affetti da disturbi dello spettro schizofrenico/bipolare provenienti da Chioggia. [Tesi di dottorato]

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Abstract (inglese)

In order to identify susceptibility loci for schizophrenia (SZ) and bipolar disorder (BPD), we collected clinical informations and biological sample of patients affected by SZ, BPD and schizoaffective disorder (SA), in collaboration with Mental Health Centre of Chioggia.
Recent findings, emerging from genetic studies, support the evidence that these diseases share a number of susceptibility genes. Accordig to this theory, we carried out genetic and molecular analysis to better undestand schizophrenia and its associated disorders in their genetic context.
By performing these analysis we were able to:
1) Collect clinical and anagraphical informations about the 40 pedigrees with high loading for schizophrenia and bipolar disorder. For each family, pedigree structure was traced back to tree generations using both church registers and demographical records. Additionally, we genotyped microsatellite markers on chromosome Y to evaluate the possibility of common male ancestor.
2) Assess the weight of genetic component and the mode of inheritance of SZ/BPD, in the pedigrees. We performed a complex segregation analysis (in collaboration with Prof. Scapoli); the results suggest that a main additive gene, plus a residual polygenic component is the best fitting hereditary model for the collected sample (Scapoli et al., 2006).
3) Find susceptibility loci with a genome wide search (GWS) in 16 multigenerational pedigrees with a high loading of the diseases (57 subjects). We genotyped 489 microsatellite markers (465 in the first scan and 24 in the fine-mapping analysis) and we calculated, using a multipoint approach, LOD score parametric and non parametric (NPL). The higher LOD score was obtained on chromosome 15q26, with a peak on marker D15S1014 (NPL=3.05), that reaches the statistical criteria for suggestive linkage (genomic P value of 0.07).
In this region (15q26) mapped the gene ST8SIA2. Recently, two SNPs located in the promoter of the gene were reported in association with schizophrenia in a Japanese and Chinese sample. In order to test the frequencies of these polimorfisms, we performed a preliminary analysis in a sample of 156 Italian subjects: 56 patients and 100 healthy subjects (50 from Chioggia and 50 from other Italian regions). The SNPs analyzed resulted to be rare or not polymorphic at all, both in Chioggia and in the general Italian population, so they are unlikely to be directly involved in schizophrenia in our population.
In order to test the possibility that some families share minor susceptibility loci not identified in the previous analysis, we evaluated linkage data for each single family separately. We found that 2 of the 16 pedigrees showed high LOD score values in 3q24-27 and 18q23, therefore in these regions a further investigations, increasing the marker density and analysing the haplotypes, were carried out. In this way, we were able to reveal on chromosome 3q24-27 a putative common haplotype shared between a subset of families. With a similar approach on chromosome 18q23 we were not able to identify a good segregation shared among other pedigrees.
4) Evaluate a possible involvement of mitochondrial polymorphisms in the pathogenesis of psychiatric disease. We characterized the mt haplogroups (Hg) and haplotypes (HVI region) of 86 index cases; the distribution of the Hg were similar to those reported for a large sample of the general Italian population so we were not able to find any significant differecies in the distribution of the haplogrups. Interestingly, we identified 12 lineages that seem to be shared between different families. These data suggest that:
- families that share the same mtDNA could have a same maternal ancestor;
- the shared mitochondria could carry a particular set of polymorphisms that influence the genetic predisposition to SZ and BPD.


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Tipo di EPrint:Tesi di dottorato
Relatore:Mostacciuolo, Maria Luisa
Correlatore:Vazza, Giovanni
Dottorato (corsi e scuole):Ciclo 20 > Scuole per il 20simo ciclo > BIOSCIENZE > GENETICA E BIOLOGIA MOLECOLARE DELLO SVILUPPO
Data di deposito della tesi:Gennaio 2008
Anno di Pubblicazione:Gennaio 2008
Parole chiave (italiano / inglese):loci di suscettibilità , schizofrenia, disturbo bipolare
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/18 Genetica
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:862
Depositato il:26 Set 2008
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Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

1. Abecasis GR, Cherny SS, Cookson WO, Cardon LR. Merlin--rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet. 2002 Jan;30(1):97-101. Cerca con Google

2. American Psychiatric Association. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. American Psychiatric Association Washington DC, 1994. Cerca con Google

3. Arai M, Yamada K, Toyota T, Obata N, Haga S, Yoshida Y, Nakamura K, Minabe Y, Ujike H, Sora I, Ikeda K, Mori N, Yoshikawa T, Itokawa M. Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia. Biol Psychiatry. 2006 Apr 1;59(7):652-9. Cerca con Google

4. Bailer U, Leisch F, Meszaros K, Lenzinger E, Willinger U, Strobl R, Gebhardt C, Gerhard E, Fuchs K, Sieghart W, Kasper S, Hornik K, Aschauer HN. Genome scan for susceptibility loci for schizophrenia. Neuropsychobiology. 2000;42(4):175-82. Cerca con Google

5. Ben-Shachar D, Laifenfeld D. Mitochondria, synaptic plasticity, and schizophrenia. Int Rev Neurobiol. 2004;59:273-96. Review. Cerca con Google

6. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ. Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am J Hum Genet. 2001 Aug;69(2):428-33. Cerca con Google

7. Bourgain C, Hoffjan S, Nicolae R, Newman D, Steiner L, Walker K, Reynolds R, Ober C, McPeek MS. Novel case-control test in a founder population identifies P-selectin as an atopysusceptibility locus. Am J Hum Genet. 2003 Sep;73(3):612-26. Cerca con Google

8. Butler JM, Schoske R, Vallone PM, Kline MC, Redd AJ, Hammer MF. A novel multiplex for simultaneous amplification of 20 Y chromosome STR markers. Forensic Sci Int. 2002 Sep 10;129(1):10-24. Cerca con Google

9. Camp NJ, Neuhausen SL, Tiobech J, Polloi A, Coon H, Myles-Worsley M. Genomewide multipoint linkage analysis of seven extended Palauan pedigrees with schizophrenia, by a Markov-chain Monte Carlo method. Am J Hum Genet. 2001 Dec;69(6):1278-89. Cerca con Google

10. Cardno AG, Jones LA, Murphy KC, Sanders RD, Asherson P, Owen MJ, McGuffin P. Dimensions of psychosis in affected sibling pairs. Schizophr Bull. 1999;25(4):841-50. Cerca con Google

11. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet. 2004 Nov;75(5):807-21. Cerca con Google

12. Cheng R, Juo SH, Loth JE, Nee J, Iossifov I, Blumenthal R, Sharpe L, Kanyas K, Lerer B, Lilliston B, Smith M, Trautman K, Gilliam TC, Endicott J, Baron M. Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder. Mol Psychiatry. 2006 Mar;11(3):252-60. Cerca con Google

13. Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK. The DISC locus in psychiatric illness. Mol Psychiatry. 2008 Jan;13(1):36-64. Cerca con Google

14. Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, Puech A, Tahri N, Cohen-Akenine A, Delabrosse S, Lissarrague S, Picard FP, Maurice K, Essioux L, Millasseau P, Grel P, Debailleul V, Simon AM, Caterina D, Dufaure I, Malekzadeh K, Belova M, Luan JJ, Bouillot M, Sambucy JL, Primas G, Saumier M, Boubkiri N, Martin-Saumier S, Nasroune M, Peixoto H, Delaye A, Pinchot V, Bastucci M, Guillou S, Chevillon M, Sainz-Fuertes R, Meguenni S, Aurich-Costa J, Cherif D, Gimalac A, Van Duijn C, Gauvreau D, Ouellette G, Fortier I, Raelson J, Sherbatich T, Riazanskaia N, Rogaev E, Raeymaekers P, Aerssens J, Konings F, Luyten W, Macciardi F, Sham PC, Straub RE, Weinberger DR, Cohen N, Cohen D. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13675-80. Cerca con Google

15. Craddock N, O'Donovan MC, Owen MJ. The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J Med Genet. 2005 Mar;42(3):193-204. Review. Cerca con Google

16. Craddock N, Owen MJ. The beginning of the end for the Kraepelinian dichotomy. Br J Psychiatry 2005; 186:364-366 Cerca con Google

17. De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G, Bonafe M, Monti D, Baggio G, Bertolini S, Mari D, Mattace R, Franceschi C. Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J. 1999 Sep;13(12):1532-6. Cerca con Google

18. Excoffier L, Smouse PE, Quattro JM. Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data. Genetics. 1992 Jun;131(2):479-91. Cerca con Google

19. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger JI Jr, Goldin LR, Bunney WE Jr. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch Gen Psychiatry. 1982 Oct;39(10):1157-67. Cerca con Google

20. Ghezzi D, Marelli C, Achilli A, Goldwurm S, Pezzoli G, Barone P, Pellecchia MT, Stanzione P, Brusa L, Bentivoglio AR, Bonuccelli U, Petrozzi L, Abbruzzese G, Marchese R, Cortelli P, Grimaldi D, Martinelli P, Ferrarese C, Garavaglia B, Sangiorgi S, Carelli V, Torroni A, Albanese A, Zeviani M. Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson's disease in Italians. Eur J Hum Genet. 2005 Jun;13(6):748-52. Cerca con Google

21. Green EK, Raybould R, Macgregor S, Gordon-Smith K, Heron J, Hyde S, Grozeva D, Hamshere M, Williams N, Owen MJ, O'Donovan MC, Jones L, Jones I, Kirov G, Craddock N. Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder. Arch Gen Psychiatry. 2005 Jun;62(6):642-8. Cerca con Google

22. Hamshere ML, Bennett P, Williams N, Segurado R, Cardno A, Norton N, Lambert D, Williams H, Kirov G, Corvin A, Holmans P, Jones L, Jones I, Gill M, O'Donovan MC, Owen MJ, Craddock N. Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Arch Gen Psychiatry. 2005 Oct;62(10):1081-8. Cerca con Google

23. Hosák L. Role of the COMT gene Val158Met polymorphism in mental disorders: a review. Eur Psychiatry. 2007 Jul;22(5):276-81. Cerca con Google

24. Herrnstadt C, Howell N. An evolutionary perspective on pathogenic mtDNA mutations: haplogroup associations of clinical disorders. Mitochondrion. 2004 Sep;4(5-6):791-8. Cerca con Google

25. Klei L, Bacanu SA, Myles-Worsley M, Galke B, Xie W, Tiobech J, Otto C, Roeder K, Devlin B, Byerley W. Linkage analysis of a completely ascertained sample of familial schizophrenics and bipolars from Palau, Micronesia. Hum Genet. 2005 Aug;117(4):349-56. Cerca con Google

26. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES. Parametric and nonparametric linkage analysis: a unified multipoint approach. Am J Hum Genet. 1996 Jun;58(6):1347-63. Cerca con Google

27. Lalouel JM, Rao DC, Morton NE, Elston RC. A unified model for complex segregation analysis. Am J Hum Genet. 1983 Sep;35(5):816-26. Cerca con Google

28. Lake CR, Hurwitz N. Schizoaffective disorder merges schizophrenia and bipolar disorders as one disease: there is no schizoaffective disorder. Curr Opin Psychiatry. 2007 Jul;20(4):365-79. Review. Cerca con Google

29. McDonald C, Murphy KC. The new genetics of schizophrenia. Psychiatr Clin North Am. 2003 Mar;26(1):41-63. Review. Cerca con Google

30. Magri C, Gardella R, Barlati SD, Valsecchi P, Sacchetti E, Barlati S. Mitochondrial DNA haplogroups and age at onset of schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144(4):496-501. Cerca con Google

31. Maziade M, Roy MA, Chagnon YC, Cliche D, Fournier JP, Montgrain N, Dion C, Lavallée JC, Garneau Y, Gingras N, Nicole L, Pirès A, Ponton AM, Potvin A, Wallot H, Mérette C. Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families. Mol Psychiatry. 2005 May;10(5):486-99. Cerca con Google

32. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215. Cerca con Google

33. Moller HJ. Bipolar disorder and schizophrenia: distinct illnesses or a continuum? J Clin Psychiatry 2003; 64[suppl 6]: 23-27. Cerca con Google

34. Onstad S, Skre I, Torgersen S, Kringlen E. Twin concordance for DSM-III-R schizophrenia. Acta Psychiatr Scand. 1991 May;83(5):395-401. Cerca con Google

35. Owen MJ, Craddock N, Jablensky A. The genetic deconstruction of psychosis. Schizophr Bull. 2007 Jul;33(4):905-11. Review. Cerca con Google

36. Park N, Juo SH, Cheng R, Liu J, Loth JE, Lilliston B, Nee J, Grunn A, Kanyas K, Lerer B, Endicott J, Gilliam TC, Baron M. Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. Mol Psychiatry. 2004 Dec;9(12):1091-9. Cerca con Google

37. Peltonen L, Palotie A, Lange K. Use of population isolates for mapping complex traits. Nat Rev Genet 2000; 1:182-190. Cerca con Google

38. Prasad S, Semwal P, Deshpande S, Bhatia T, Nimgaonkar VL, Thelma BK. Molecular genetics of schizophrenia: past, present and future. J Biosci. 2002 Feb;27(1 Suppl 1):35-52. Review. Cerca con Google

39. Pritchard JK, Rosenberg NA. Use of unlinked genetic markers to detect population stratification in association studies. Am J Hum Genet. 1999 Jul;65(1):220-8. Cerca con Google

40. Sanders AR, Duan J, Gejman PV. Complexities in psychiatric genetics. Int Rev Psychiatry. 2004 Nov;16(4):284-93. Review. Cerca con Google

41. Scapoli C, Rampinelli S, Vazza G, Peruzzi P, De Sanctis G, Di Florio A, Bertolin C., Mostacciuolo Ml. Genetic inheritance of schizophrenia and bipolar disorder in an Italian population isolate. Am J Med Genet B Neuropsychiatr Genet. 2006 vol. 141B, pp. 719-720 Cerca con Google

42. Schosser A, Fuchs K, Scharl T, Leisch F, Bailer U, Kasper S, Sieghart W, Hornik K, Aschauer HN. Additional support for linkage of schizophrenia and bipolar disorder to chromosome 3q29. Eur Neuropsychopharmacol. 2007 May-Jun;17(6-7):501-5. Cerca con Google

43. Schumacher J, Jamra RA, Freudenberg J, Becker T, Ohlraun S, Otte AC, Tullius M, Kovalenko S, Bogaert AV, Maier W, Rietschel M, Propping P, Nöthen MM, Cichon S. Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder. Cerca con Google

44. Mol Psychiatry. 2004 Feb;9(2):203-7. Cerca con Google

45. Sklar P, Pato MT, Kirby A, Petryshen TL, Medeiros H, Carvalho C, Macedo A, Dourado A, Coelho I, Valente J, Soares MJ, Ferreira CP, Lei M, Verner A, Hudson TJ, Morley CP, Kennedy JL, Azevedo MH, Lander E, Daly MJ, Pato CN. Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis. Mol Psychiatry. 2004 Feb;9(2):213-8. Cerca con Google

46. Smoller JW, Finn CT. Family, twin, and adoption studies of bipolar disorder. Am J Med Genet (Semin Med Genet) 2003; 123:48-58. Cerca con Google

47. Strachan T, Read AP. Genetica umana molecolare(3^edizione). UTET, 2006 Cerca con Google

48. Tao R, Li C, Zheng Y, Qin W, Zhang J, Li X, Xu Y, Shi YY, Feng G, He L. Positive association between SIAT8B and schizophrenia in the Chinese Han population. Schizophr Res. 2007 Feb;90(1-3):108-14. Cerca con Google

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