Quantitative Trait Locus Mapping of Genes That Regulate Phospholipid Transfer Activity in SM/J and NZB/B1NJ Inbred Mice
Authors - Ron Korstanje, John J. Albers, Gertrud Wolfbauer,
Renhua Li, An-Yue Tu, Gary A. Churchill, Beverly J. Paigen
Objective—Phospholipid transfer protein (PLTP), an important protein in the transfer of phospholipids between lipoprotein particles and in the remodeling of HDL, is regulated at both the transcriptional and the protein level. We performed quantitative trait locus (QTL) analysis to identify genomic loci regulating PLTP activity in mice.
Methods and Results—Plasma PLTP activity was measured in 217 male F2 progeny from a SM/J x NZB/B1NJ intercross. Two QTL for plasma PLTP activity in mice fed chow (Pltpql and Pltpq2) were found on chromosomes 3 (34 cM, logarithm of odds [LOD] 3.5) and 10 (66 cM, LOD 4.1); two additional QTL in mice fed atherogenic diet (Pltpq3 and Pltpq4) were found on chromosomes 9 (56 cM, LOD 4.5) and 15 (34 cM, LOD 5.0); and one QTL (Pltiql) for the inducibility of PLTP activity was found on chromosome 4 (70 cM, LOD 3.7).Several candidate genes for these 5 QTL were tested by sequence comparison and expression studies.
Conclusions—We identified 5 significant loci involved in PLTP activity in the mouse and provided supporting evidence for the candidacy of Nrlh4 and Apof as the genes underlying Pltpq2. (Arterioscler Thromb Vase Biol. 2004;24:l-7.)
Table 1. QTL for PLTP activity identified in the NZB x SM intercross. For each of the three analyzed phenotypes (PLTP on chow, PLTP on high fat diet, and the log of the ratio between the two diets) the significant QTL are shown with their chromosomal position, maximum LOD score, 95% confidence interval (CI), and the allele effect. The allele effect shows the high allele (allele with the highest PLTP activity) and the mode of inheritance (dominant, additive, or recessive).
|
Traits |
Name |
Chr |
Location (cM) |
95% CI (cM) |
Max LOD |
Peak marker |
High allele (inheritance) |
Candidate genes (cM) |
|
PLTP (chow) |
Pltpq1 |
3 |
34 |
30-45 |
3.5 |
D3Mit22 |
NZB (additive) |
Apo1bp (40) |
|
|
Pltpq2
|
10 |
66 |
55-70 |
4.1 |
D10Mit271 |
Heterozygotes |
Nr1h4 (50), Apof (73) |
|
PLTP (fat) |
Pltpq3 |
9 |
56 |
50-60 |
4.5 |
D9Mit15 |
NZB (recessive) |
Scap (61) |
|
|
Pltpq4 |
15 |
34 |
30-45 |
5.0 |
D15Mit90 |
SM (additive) |
Ppara (50) |
|
|
|
|
|
|
|
|
|
|
|
PLTP inducibility |
Pltiq1 |
4 |
70 |
60-80 |
3.7 |
D4Mit312 |
NZB (dominant) |
Nr0b2 (60) |
Genome scan
Detailed QTL plots with allele effects
* P<0.05 compared with S/S.
† P<0.05 with S/N.
