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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
05:53

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Published on: June 21, 2018

Genetic screening of candidate genes for a prothrombotic interaction with type I protein C deficiency in a large

B T Scott1, E G Bovill, P W Callas

  • 1Department of Pathology, University of Vermont, Burlington 05405, USA.

Thrombosis and Haemostasis
|February 24, 2001
PubMed

Insights

In familial protein C deficiency, thrombosis risk increases with additional hemostatic abnormalities. A study found no evidence implicating 34 candidate genes as the second inherited factor for thrombophilia in the Vermont II kindred.

Area of Science:

  • Genetics
  • Hematology
  • Molecular Biology

Background:

  • Familial protein C deficiency exhibits incomplete penetrance for thrombosis, suggesting additional genetic factors contribute to disease.
  • The Vermont II kindred, with dominant Type I protein C deficiency, shows a pattern of inherited thrombophilia indicative of a second, independent gene.
  • Investigating this second gene is crucial for understanding the complex genetic basis of thrombophilia.

Purpose of the Study:

  • To test the hypothesis of a second unidentified gene contributing to thrombophilia in the Vermont II kindred.
  • To identify potential candidate genes involved in hemostasis or inflammation that segregate with increased thrombosis risk.
  • To analyze linkage between candidate genes and thrombophilia within the kindred.

Main Methods:

  • Candidate gene association study utilizing linkage analysis.
  • Screening of 34 candidate genes involved in hemostasis and inflammation.
  • Employment of highly polymorphic short tandem repeat (STR) markers in an informative subset (n=31) of the kindred.

Main Results:

  • Linkage analysis was performed on 34 candidate genes, including fibrinogens, prothrombin, factors V, XI, XII, XIII, von Willebrand factor, and others.
  • Despite investigating numerous genes known as independent risk factors for thrombosis, none showed linkage to the increased thrombophilia in this kindred.
  • No evidence was found to implicate any of the tested candidate genes as the second inherited factor responsible for thrombophilia.

Conclusions:

  • The study failed to identify the second gene responsible for increased thrombophilia in the Vermont II kindred among the 34 candidate genes tested.
  • The genetic basis for the incomplete penetrance of thrombosis in familial protein C deficiency remains to be elucidated.
  • Further research is needed to identify the unknown genetic factor(s) contributing to thrombophilia in this and similar kindreds.

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