on February 23, 2006
Published online before print February 23, 2006, doi: 10.1161/01.STR.0000206153.92675.b9
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 13, 2005
From the Departments of Neurosurgery (A.K.O., B.V.N., M.B., K.B., E.G., G.B., B.G., A.A., M.G.), Radiology (M.H.J.), Genetics (R.P.L.), and Neurobiology (M.G.), and Howard Hughes Medical Institute (R.P.L.), Yale University School of Medicine, New Haven, Conn; Marmara University (K.B.) Istanbul, Turkey; Akdeniz University (E.G.) Antoly, Turkey; Kirikkale University (G.B.) Kirikkale, Turkey; and Yeditepe University (B.G.), Istanbul, Turkey. * To whom correspondence should be addressed. E-mail: murat.gunel{at}yale.edu.
Background and Purpose--Both environmental and genetic factors contribute to the formation, growth, and rupture of intracranial aneurysms (IAs). To search for IA susceptibility genes, we took an outlier approach, using parametric genome-wide linkage analysis in extended IA kindreds in which IA is inherited as a simple Mendelian trait. We hereby present the molecular genetic analysis of 2 such families. Methods--For genome-wide linkage analysis, we used a 2-stage approach. First, using gene chips in affected-only analysis, we identified genomic regions that provide maximum theoretical logarithm of odds (lod) scores. Next, to confirm or exclude these candidate loci, we genotyped all available family members, both affected and unaffected, using polymorphic microsatellite markers located within these regions. Results--We obtained significant lod scores of 4.3 and 3.00 for linkage to chromosomes 11q24-25 and 14q23-31, respectively. Conclusions--Molecular genetic analysis of 2 large IA kindreds confirms linkage to chromosome 11q and 14q, which were suggested to contain IA susceptibility genes in a previous study of Japanese sib pairs. Independent identification of these 2 loci strongly suggests that IA susceptibility genes lie within these regions. While demonstrating the genetic heterogeneity of IA, these results are also an important step toward cloning IA genes and ultimately understanding its pathophysiology.
Revised on November 28, 2005
Accepted on December 20, 2005
Molecular Genetic Analysis of Two Large Kindreds With Intracranial Aneurysms Demonstrates Linkage to 11q24-25 and 14q23-31
Ali K. Ozturk BA;
Key words: aneurysm • genetics
This article has been cited by other articles:
 |
|
 |
|
  F. Xu, M. L. Previti, M. T. Nieman, J. Davis, A. H. Schmaier, and W. E. Van Nostrand A{beta}PP/APLP2 Family of Kunitz Serine Proteinase Inhibitors Regulate Cerebral Thrombosis J. Neurosci., April 29, 2009; 29(17): 5666 - 5670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Santiago-Sim, S. R. DePalma, K. L. Ju, B. McDonough, C. E. Seidman, J.G. Seidman, and D. H. Kim Genomewide Linkage in a Large Caucasian Family Maps a New Locus for Intracranial Aneurysms to Chromosome 13q Stroke, March 1, 2009; 40(3_suppl_1): S57 - S60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Woo, J. Khoury, M. M. Haverbusch, P. Sekar, M. L. Flaherty, D. O. Kleindorfer, B. M. Kissela, C. J. Moomaw, R. Deka, and J. P. Broderick Smoking and family history and risk of aneurysmal subarachnoid hemorrhage Neurology, January 6, 2009; 72(1): 69 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. B. Worrall, T. Foroud, R. D. Brown Jr, E. Sander. Connolly, R. W. Hornung, J. Huston III, D. Kleindorfer, D. L. Koller, D. Lai, C. J. Moomaw, et al. Genome Screen to Detect Linkage to Common Susceptibility Genes for Intracranial and Aortic Aneurysms Stroke, January 1, 2009; 40(1): 71 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Fischer, J Kohlhase, D Bohm, B Schweiger, D Hoffmann, M Heitmann, B Horsthemke, and D Wieczorek Biallelic loss of function of the promyelocytic leukaemia zinc finger (PLZF) gene causes severe skeletal defects and genital hypoplasia J. Med. Genet., November 1, 2008; 45(11): 731 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Foroud, L. Sauerbeck, R. Brown, C. Anderson, D. Woo, D. Kleindorfer, M. L. Flaherty, R. Deka, R. Hornung, I. Meissner, et al. Genome Screen to Detect Linkage to Intracranial Aneurysm Susceptibility Genes: The Familial Intracranial Aneurysm (FIA) Study Stroke, May 1, 2008; 39(5): 1434 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Ruigrok, C. Wijmenga, G. J.E. Rinkel, R. v. Slot, F. Baas, M. Wolfs, A. Westerveld, and Y. B.W.E.M. Roos Genomewide Linkage in a Large Dutch Family With Intracranial Aneurysms: Replication of 2 Loci for Intracranial Aneurysms to Chromosome 1p36.11-p36.13 and Xp22.2-p22.32 Stroke, April 1, 2008; 39(4): 1096 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Ruigrok and G. J.E. Rinkel Genetics of Intracranial Aneurysms Stroke, March 1, 2008; 39(3): 1049 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Weinsheimer, G. M. Lenk, M. van der Voet, S. Land, A. Ronkainen, I. Alafuzoff, H. Kuivaniemi, and G. Tromp Integration of expression profiles and genetic mapping data to identify candidate genes in intracranial aneurysm Physiol Genomics, December 19, 2007; 32(1): 45 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Weinsheimer, K. A.B. Goddard, A. R. Parrado, Q. Lu, M. Sinha, E. R. Lebedeva, A. Ronkainen, M. Niemela, E. K. Khusnutdinova, R. I. Khusainova, et al. Association of Kallikrein Gene Polymorphisms With Intracranial Aneurysms Stroke, October 1, 2007; 38(10): 2670 - 2676. [Abstract] [Full Text] [PDF]
|
|