Evidence for linkage of the apolipoprotein A-II locus to plasma apolipoprotein A-II and free fatty acid levels in mice and humans
| Autor: | R M Gray, Craig H Warden, D A Purcell-Huynh, Yi Chen, Donald L. Puppione, C De Meester, B H Shieh, Xiangdong Bu, Gerald M. Reaven, Aaron Daluiski |
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| Rok vydání: | 1993 |
| Předmět: |
Apolipoprotein B
Genetic Linkage Apolipoprotein A-II Coronary Disease Mice Transgenic Locus (genetics) Fatty Acids Nonesterified Quantitative trait locus Mice Centimorgan Gene mapping Genetic linkage Animals Humans Gene Genetics Multidisciplinary biology Pedigree Mice Inbred C57BL Muridae Genes biology.protein Regression Analysis Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 90:10886-10890 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.90.22.10886 |
| Popis: | Although it has been hypothesized that the synteny between mouse and human genes provides an approach to the localization of genes that determine quantitative traits in humans, this has yet to be demonstrated. We tested this approach with two quantitative traits, plasma apolipoprotein A-II (apoAII) and free fatty acid (FFA) levels. ApoAII is the second most abundant protein of high density lipoprotein particles, but its function remains largely unknown. We now show that, in a backcross between strains Mus spretus and C57BL/6J, apoAII levels correlate with plasma FFA concentrations on both chow (P < 0.0001) and high-fat (P < 0.0003) diets and that apoAII levels are linked to the apoAII gene (P < 0.0002). To test whether variations of the apoAII gene influence plasma lipid metabolism in humans, we studied 306 individuals in 25 families enriched for coronary artery disease. The segregation of the apoAII gene was followed by using an informative simple sequence repeat in the second intron of the gene and two nearby genetic markers. Robust sib-pair linkage analysis was performed on members of these families using the SAGE linkage programs. The results suggest linkage between the human apoAII gene and a gene controlling plasma apoAII levels (P = 0.03). Plasma apoAII levels were also significantly correlated with plasma FFA levels (P = 0.007). Moreover, the apoAII gene exhibited linkage with a gene controlling FFA levels (P = 0.003). Evidence for nonrandom segregation was seen with markers as far as 6-12 centimorgans from the apoAII structural locus. These data provide evidence, in two species, that the apoAII gene is linked to a gene that controls plasma apoAII levels and that apoAII influences, by an unknown mechanism, plasma FFA levels. The results illustrate the utility of animal studies for analysis of complex traits. |
| Databáze: | OpenAIRE |
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