The effect of variation in the apolipoprotein B gene on plasmid lipid and apolipoprotein B levels. I. A likelihood-based approach to cladistic analysis

Ann Hum Genet. 1994 Jan;58(1):35-64. doi: 10.1111/j.1469-1809.1994.tb00724.x.

Abstract

A new method is described for employing family data to test for significant haplotype effects on continuously distributed variables, using likelihood-ratio tests of linear models in which haplotype effects are parameterized and familial correlations taken into account. The method is applied to the apolipoprotein B (Apo B) gene, using 5 polymorphisms (Insertion/deletion, Bsp1286I, XbaI, MspI, EcoRI) to define haplotypes in 121 French nuclear families. Eleven haplotypes were found, five of which, combined, account for over 95% of the sample. A haplotype phylogeny is proposed, and is used to define a nested set of models for testing the effects of Apo B variation on total-, low-density-lipoprotein (LDL)-, and high-density-lipoprotein (HDL)-cholesterol, triglyceride, and Apo B levels. Apo B haplotype effects account for about 10% of the genetic variance and 5% of the total variance in HDL-cholesterol and triglyceride levels. Clusters of evolutionarily-related haplotypes with similar phenotypic effects are identified for HDL-cholesterol and triglycerides. Single haplotypes with statistically significant effects are identified for cholesterol, LDL-cholesterol, and Apo B levels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Apolipoproteins B / analysis
  • Apolipoproteins B / genetics*
  • Base Sequence
  • Child
  • Female
  • France
  • Gene Frequency
  • Genetic Variation / genetics*
  • Haplotypes*
  • Humans
  • Linear Models
  • Lipids / blood*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Phylogeny
  • Polymorphism, Genetic*

Substances

  • Apolipoproteins B
  • Lipids