Familial thoracic aortic aneurysms and dissections genetic: Heterogeneity with a major locus mapping to 5q13-14

Dongchuan Guo, Sumera Hasham, Shao Qing Kuang, Carl J. Vaughan, Eric Boerwinkle, Hua Chen, Dianne Abuelo, Harry C Dietz, Craig T. Basson, Sanjay S. Shete, Dianna M. Milewicz

Research output: Contribution to journalArticle

Abstract

Background - Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of the aortic media, called medial necrosis. Families identified with dominant inheritance of thoracic aortic aneurysms and dissections (TAA/dissections) indicate that single gene mutations can cause medial necrosis in the absence of an associated syndrome. Methods and Results - Fifteen families were identified with multiple members with TAAs/dissections. DNA from affected members from 2 of the families was used for a genome-wide search for the location of the defective gene by use of random polymorphic markers. The data were analyzed by the affected-pedigree-member method of linkage analysis. This analysis revealed 3 chromosomal loci with multiple markers demonstrating evidence of linkage to the phenotype. Linkage analysis using further markers in these regions and DNA from 15 families confirmed linkage of some of the families to 5q13-14. Genetic heterogeneity for the condition was confirmed by a heterogeneity test. Data from 9 families with the highest conditional probability of being linked to 5q were used to calculate the pairwise and multipoint logarithm of the odds (LOD) scores, with a maximum LOD of 4.74, with no recombination being obtained for the marker D5S2029. In 6 families, the phenotype was not linked to the 5q locus. Conclusions - A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.

Original languageEnglish (US)
Pages (from-to)2461-2468
Number of pages8
JournalCirculation
Volume103
Issue number20
StatePublished - May 22 2001

Fingerprint

Genetic Heterogeneity
Dissection
Aneurysm
Necrosis
Phenotype
Familial Thoracic 1 Aortic Aneurysm
Thoracic Aortic Aneurysm
DNA
Pedigree
Genetic Recombination
Genes
Aorta
Genome
Mutation

Keywords

  • Aneurysm
  • Aorta
  • Genetics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Guo, D., Hasham, S., Kuang, S. Q., Vaughan, C. J., Boerwinkle, E., Chen, H., ... Milewicz, D. M. (2001). Familial thoracic aortic aneurysms and dissections genetic: Heterogeneity with a major locus mapping to 5q13-14. Circulation, 103(20), 2461-2468.

Familial thoracic aortic aneurysms and dissections genetic : Heterogeneity with a major locus mapping to 5q13-14. / Guo, Dongchuan; Hasham, Sumera; Kuang, Shao Qing; Vaughan, Carl J.; Boerwinkle, Eric; Chen, Hua; Abuelo, Dianne; Dietz, Harry C; Basson, Craig T.; Shete, Sanjay S.; Milewicz, Dianna M.

In: Circulation, Vol. 103, No. 20, 22.05.2001, p. 2461-2468.

Research output: Contribution to journalArticle

Guo, D, Hasham, S, Kuang, SQ, Vaughan, CJ, Boerwinkle, E, Chen, H, Abuelo, D, Dietz, HC, Basson, CT, Shete, SS & Milewicz, DM 2001, 'Familial thoracic aortic aneurysms and dissections genetic: Heterogeneity with a major locus mapping to 5q13-14', Circulation, vol. 103, no. 20, pp. 2461-2468.
Guo D, Hasham S, Kuang SQ, Vaughan CJ, Boerwinkle E, Chen H et al. Familial thoracic aortic aneurysms and dissections genetic: Heterogeneity with a major locus mapping to 5q13-14. Circulation. 2001 May 22;103(20):2461-2468.
Guo, Dongchuan ; Hasham, Sumera ; Kuang, Shao Qing ; Vaughan, Carl J. ; Boerwinkle, Eric ; Chen, Hua ; Abuelo, Dianne ; Dietz, Harry C ; Basson, Craig T. ; Shete, Sanjay S. ; Milewicz, Dianna M. / Familial thoracic aortic aneurysms and dissections genetic : Heterogeneity with a major locus mapping to 5q13-14. In: Circulation. 2001 ; Vol. 103, No. 20. pp. 2461-2468.
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abstract = "Background - Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of the aortic media, called medial necrosis. Families identified with dominant inheritance of thoracic aortic aneurysms and dissections (TAA/dissections) indicate that single gene mutations can cause medial necrosis in the absence of an associated syndrome. Methods and Results - Fifteen families were identified with multiple members with TAAs/dissections. DNA from affected members from 2 of the families was used for a genome-wide search for the location of the defective gene by use of random polymorphic markers. The data were analyzed by the affected-pedigree-member method of linkage analysis. This analysis revealed 3 chromosomal loci with multiple markers demonstrating evidence of linkage to the phenotype. Linkage analysis using further markers in these regions and DNA from 15 families confirmed linkage of some of the families to 5q13-14. Genetic heterogeneity for the condition was confirmed by a heterogeneity test. Data from 9 families with the highest conditional probability of being linked to 5q were used to calculate the pairwise and multipoint logarithm of the odds (LOD) scores, with a maximum LOD of 4.74, with no recombination being obtained for the marker D5S2029. In 6 families, the phenotype was not linked to the 5q locus. Conclusions - A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.",
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T2 - Heterogeneity with a major locus mapping to 5q13-14

AU - Guo, Dongchuan

AU - Hasham, Sumera

AU - Kuang, Shao Qing

AU - Vaughan, Carl J.

AU - Boerwinkle, Eric

AU - Chen, Hua

AU - Abuelo, Dianne

AU - Dietz, Harry C

AU - Basson, Craig T.

AU - Shete, Sanjay S.

AU - Milewicz, Dianna M.

PY - 2001/5/22

Y1 - 2001/5/22

N2 - Background - Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of the aortic media, called medial necrosis. Families identified with dominant inheritance of thoracic aortic aneurysms and dissections (TAA/dissections) indicate that single gene mutations can cause medial necrosis in the absence of an associated syndrome. Methods and Results - Fifteen families were identified with multiple members with TAAs/dissections. DNA from affected members from 2 of the families was used for a genome-wide search for the location of the defective gene by use of random polymorphic markers. The data were analyzed by the affected-pedigree-member method of linkage analysis. This analysis revealed 3 chromosomal loci with multiple markers demonstrating evidence of linkage to the phenotype. Linkage analysis using further markers in these regions and DNA from 15 families confirmed linkage of some of the families to 5q13-14. Genetic heterogeneity for the condition was confirmed by a heterogeneity test. Data from 9 families with the highest conditional probability of being linked to 5q were used to calculate the pairwise and multipoint logarithm of the odds (LOD) scores, with a maximum LOD of 4.74, with no recombination being obtained for the marker D5S2029. In 6 families, the phenotype was not linked to the 5q locus. Conclusions - A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.

AB - Background - Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of the aortic media, called medial necrosis. Families identified with dominant inheritance of thoracic aortic aneurysms and dissections (TAA/dissections) indicate that single gene mutations can cause medial necrosis in the absence of an associated syndrome. Methods and Results - Fifteen families were identified with multiple members with TAAs/dissections. DNA from affected members from 2 of the families was used for a genome-wide search for the location of the defective gene by use of random polymorphic markers. The data were analyzed by the affected-pedigree-member method of linkage analysis. This analysis revealed 3 chromosomal loci with multiple markers demonstrating evidence of linkage to the phenotype. Linkage analysis using further markers in these regions and DNA from 15 families confirmed linkage of some of the families to 5q13-14. Genetic heterogeneity for the condition was confirmed by a heterogeneity test. Data from 9 families with the highest conditional probability of being linked to 5q were used to calculate the pairwise and multipoint logarithm of the odds (LOD) scores, with a maximum LOD of 4.74, with no recombination being obtained for the marker D5S2029. In 6 families, the phenotype was not linked to the 5q locus. Conclusions - A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.

KW - Aneurysm

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