Evidence for an Interaction of Schizophrenia Susceptibility Loci on Chromosome 6q23.3 and 10q24.33-q26.13 in Arab Israeli Families

被引:10
作者
Alkelai, A. [1 ]
Kohn, Y. [1 ]
Olender, T. [2 ]
Sarner-Kanyas, K. [1 ]
Rigbi, A. [1 ]
Hamdan, A. [3 ]
Ben-Asher, E. [2 ]
Lancet, D. [2 ]
Lerer, B. [1 ]
机构
[1] Hadassah Hebrew Univ, Dept Psychiat, Med Ctr, Biol Psychiat Lab, IL-91120 Jerusalem, Israel
[2] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[3] Reg Mental Hlth Ctr, Taibe, Israel
基金
以色列科学基金会;
关键词
schizophrenia; chromosome; 10q; 6q; two locus linkage; epistasis; BIPOLAR AFFECTIVE-DISORDER; 2-TRAIT-LOCUS LINKAGE ANALYSIS; GENOME SCAN; DIAGNOSTIC CRITERIA; PARTIAL EPILEPSY; GENETIC-LINKAGE; DISEASE; MAPS; HETEROGENEITY; EXPRESSION;
D O I
10.1002/ajmg.b.30918
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
A genome scan for schizophrenia related loci in Arab Israeli families by Lerer et al. [Lerer et al. (2003); Mol Psychiatry 8:488-498] detected significant evidence for linkage at chromosome 6q23. Subsequent fine mapping [Levi et al. (2005); Eur J Hum Genet 13:763-771], association [Amann-Zalcenstein et al. (2006); Eur J Hum Genet 14:1111-1119] and replication studies (Ingason et al. (2007); Eur J Hum Genet 15:988-991] identified AHI1 as a putative susceptibility gene. The same genome scan revealed suggestive evidence for a schizophrenia susceptibility locus in the 10q23-26 region. Genes at these two loci may act independently in the pathogenesis of the disease in our homogeneous sample of Arab Israeli families or may interact with each other and with other factors in a common biological pathway. The purpose of our current study was to test the hypothesis of genetic interaction between these two loci and to identify the type of interaction between them. The initial stage of our study focused on the 10q23-q26 region which has not been explored further in our sample. The second stage of the study included a test for possible genetic interaction between the 6q23.3 locus and the refined 10q24.33-q26.13 locus. A final candidate region of 19.9 Mb between markers D10S222 (105.3 Mb) and D10S587 (125.2 Mb) was found on chromosome 10 by non-parametric and parametric linkage analyses. These linkage findings are consistent with previous reports in the same chromosomal region. Two-locus multipoint linkage analysis under three complex disease inheritance models (heterogeneity, multiplicative, and additive models) yielded a best maximum LOD score of 7.45 under the multiplicative model suggesting overlapping function of the 6q23.3 and 10q24.33-q26.13 loci. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:914 / 925
页数:12
相关论文
共 69 条
[61]   Parametric and nonparametric multipoint linkage analysis with imprinting and two-locus-trait models: Application to mite sensitization [J].
Strauch, K ;
Fimmers, R ;
Kurz, T ;
Deichmann, KA ;
Wienker, TF ;
Baur, MP .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (06) :1945-1957
[62]  
Strauch K, 2003, AM J HUM GENET, V73, P615
[63]   How to model a complex trait [J].
Strauch, K ;
Fimmers, R ;
Baur, MP ;
Wienker, TF .
HUMAN HEREDITY, 2003, 55 (04) :202-210
[64]   GRK5 deficiency leads to early Alzheimer-like pathology and working memory impairment [J].
Suo, Zhiming ;
Cox, April A. ;
Bartelli, Nicholas ;
Rasul, Lmtiaz ;
Festoff, Barry W. ;
Premont, Richard T. ;
Arendash, Gary W. .
NEUROBIOLOGY OF AGING, 2007, 28 (12) :1873-1888
[65]   Chromosome 10q harbors a susceptibility locus for bipolar disorder in Ashkenazi Jewish families [J].
Venken, T. ;
Alaerts, M. ;
Souery, D. ;
Goossens, D. ;
Sluijs, S. ;
Navon, R. ;
Van Broeckhoven, C. ;
Mendlewicz, J. ;
Del-Favero, J. ;
Claes, S. .
MOLECULAR PSYCHIATRY, 2008, 13 (04) :442-450
[66]   Recent advances in the genetics of schizophrenia [J].
Waterworth, DM ;
Bassett, AS ;
Brzustowicz, LM .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2002, 59 (02) :331-348
[67]   A two-stage genome scan for schizophrenia susceptibility genes in 196 affected sibling pairs [J].
Williams, NM ;
Rees, MI ;
Holmans, P ;
Norton, N ;
Cardno, AG ;
Jones, LA ;
Murphy, KC ;
Sanders, RD ;
McCarthy, G ;
Gray, MY ;
Fenton, I ;
McGuffin, P ;
Owen, MJ .
HUMAN MOLECULAR GENETICS, 1999, 8 (09) :1729-1739
[68]   A systematic genomewide linkage study in 353 sib pairs with schizophrenia [J].
Williams, NM ;
Norton, N ;
Williams, H ;
Ekholm, B ;
Hamshere, ML ;
Lindblom, Y ;
Chowdari, KV ;
Cardno, AG ;
Zammit, S ;
Jones, LA ;
Murphy, KC ;
Sanders, RD ;
McCarthy, G ;
Gray, MY ;
Jones, G ;
Holmans, P ;
Nimgaonkar, V ;
Adolfson, R ;
Ösby, U ;
Terenius, L ;
Sedvall, G ;
O'Donovan, MC ;
Owen, MJ .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (06) :1355-1367
[69]   Multiple mutations responsible for frequent genetic diseases in isolated populations [J].
Zlotogora, Joel .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2007, 15 (03) :272-278