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Related Experiment Videos

Linkage analysis using platelet-activating factor Ca2+ response in transformed lymphoblasts

L M Brzustowicz1, J P Gardner, L Hopp

  • 1Hypertension Research Program, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA.

Hypertension (Dallas, Tex. : 1979)
|January 1, 1997
PubMed
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Researchers identified genes linked to essential hypertension by studying calcium responses in lymphoblast cell lines. This approach uses cellular phenotypes to map genes for complex disorders in general populations.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Essential hypertension involves G protein-coupled signaling pathways.
  • Platelet-activating factor (PAF) elicits a cytosolic free calcium ([Ca2+]i) response mediated by G proteins.
  • Epstein-Barr virus-transformed lymphoblasts from hypertensive patients show enhanced PAF-induced [Ca2+]i response.

Purpose of the Study:

  • To map genes influencing G protein-coupled signaling variations.
  • To utilize the enhanced PAF-evoked [Ca2+]i response as a quantitative trait for linkage analysis.
  • To identify genetic loci associated with essential hypertension pathophysiology.

Main Methods:

  • Linkage analysis of transformed lymphoblast cell lines from CEPH reference pedigrees.

Related Experiment Videos

  • Measurement of PAF-evoked cytosolic free calcium ([Ca2+]i) responses.
  • Two-point and multipoint sibpair linkage analyses using 5150 CHLC markers.

    • Main Results:

    • Nine loci on chromosomes 1, 4, 10, 11, 13, 16, and 17 showed suggestive linkage (P < 7.4 x 10(-4)).
    • Significant linkage (P = 2.1 x 10(-5)) found at D16S151 on chromosome 16.
    • Suggestive linkage to eight loci on chromosome 11 identified.

    Conclusions:

    • Genetic loci controlling G protein-mediated signaling, relevant to essential hypertension, can be mapped using lymphoblast cell lines.
    • This strategy efficiently maps loci for complex disorders using stable phenotypes in immortalized cells.
    • The study validates an approach for identifying genes in common complex diseases using general pedigrees.