Genetic architecture of the F7 gene in a Spanish population: Implication for mapping complex diseases and for functional assays

M. Sabater-Lleal, L. Almasy, E. Martínez-Marchán, E. Martínez-Sánchez, R. Souto, J. Blangero, Jc Souto, J. Fontcuberta, José M. Soria

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Delineating the genetic variability of loci coding for complex diseases helps to understand the individual variation in disease susceptibility and drug response. We present the allelic architecture of the F7 gene. This gene is the major determinant of FVII plasma levels, and these plasma levels constitute an important intermediate risk factor for cardiovascular disease. As part of the Genetic Analysis of Idiopathic Thrombophila Project, we completely re-sequenced the F7 locus (promoter, exons, introns, and 3′-untranslated region) in 40 unrelated individuals. We found 49 polymorphisms with only two amino acid changes suggesting that regulatory non-coding and intronic variants are responsible for the FVII variability. These results are important for mapping susceptibility alleles of complex diseases, because differences in pair-wise linkage disequilibrium patterns between DNA variants and haplotype frequency distributions may help to detect disease-associated alleles. In addition, we present the results of an in silico search that established genomic comparisons among different species. In conclusion, our study of the F7 DNA sequence variations is an example of a strategy for analyzing the genetic architecture of a quantitative trait locus. Furthermore, it provides a model for future analyses of genetic factors that contribute to the susceptibility of complex diseases in humans.

Original languageEnglish (US)
Pages (from-to)420-428
Number of pages9
JournalClinical Genetics
Volume69
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

Disease Susceptibility
Alleles
Population
Genes
Genetic Loci
Quantitative Trait Loci
Linkage Disequilibrium
3' Untranslated Regions
Computer Simulation
Introns
Haplotypes
Statistical Factor Analysis
Exons
Cardiovascular Diseases
Amino Acids
DNA
Pharmaceutical Preparations

Keywords

  • Cardiovascular risk
  • Complex disease
  • F7 variation
  • FVII levels
  • Linkage analysis
  • Polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Sabater-Lleal, M., Almasy, L., Martínez-Marchán, E., Martínez-Sánchez, E., Souto, R., Blangero, J., ... Soria, J. M. (2006). Genetic architecture of the F7 gene in a Spanish population: Implication for mapping complex diseases and for functional assays. Clinical Genetics, 69(5), 420-428. https://doi.org/10.1111/j.1399-0004.2006.00608.x

Genetic architecture of the F7 gene in a Spanish population : Implication for mapping complex diseases and for functional assays. / Sabater-Lleal, M.; Almasy, L.; Martínez-Marchán, E.; Martínez-Sánchez, E.; Souto, R.; Blangero, J.; Souto, Jc; Fontcuberta, J.; Soria, José M.

In: Clinical Genetics, Vol. 69, No. 5, 05.2006, p. 420-428.

Research output: Contribution to journalArticle

Sabater-Lleal, M, Almasy, L, Martínez-Marchán, E, Martínez-Sánchez, E, Souto, R, Blangero, J, Souto, J, Fontcuberta, J & Soria, JM 2006, 'Genetic architecture of the F7 gene in a Spanish population: Implication for mapping complex diseases and for functional assays', Clinical Genetics, vol. 69, no. 5, pp. 420-428. https://doi.org/10.1111/j.1399-0004.2006.00608.x
Sabater-Lleal, M. ; Almasy, L. ; Martínez-Marchán, E. ; Martínez-Sánchez, E. ; Souto, R. ; Blangero, J. ; Souto, Jc ; Fontcuberta, J. ; Soria, José M. / Genetic architecture of the F7 gene in a Spanish population : Implication for mapping complex diseases and for functional assays. In: Clinical Genetics. 2006 ; Vol. 69, No. 5. pp. 420-428.
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