RGD Reference Report - Genome-wide scan identifies novel QTLs for cholesterol and LDL levels in F2-intercross rats. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Genome-wide scan identifies novel QTLs for cholesterol and LDL levels in F2-intercross rats.

Authors: Herrera, VL  Didishvili, T  Lopez, LV  Myers, RH  Ruiz-Opazo, N 
Citation: Herrera VL, etal., Circ Res 2004 Mar 5;94(4):446-52. Epub 2004 Jan 22.
RGD ID: 737694
Pubmed: PMID:14739155   (View Abstract at PubMed)
DOI: DOI:10.1161/01.RES.0000117770.03168.E7   (Journal Full-text)

Hypercholesterolemia is a significant risk factor for coronary artery disease development. Genes influencing nonmonogenic hypercholesterolemia susceptibility in humans remain to be identified. Animal models are key investigative systems because major confounding variables such as diet, activity, and genetic background can be controlled. We performed a 121-marker, total genome-analysis of an F2[Dahl RxS]-intercross selected for contrasting parental strain susceptibilities for hyperlipidemia on regular rat diets at 6 months of age. Quantitative traits studied were plasma total cholesterol, triglyceride, HDL, and LDL levels adjusted for obesity. Genome-wide analysis of 200 F2-intercross male rats detects two QTLs with highly significant linkage for total cholesterol (TC) on chromosome (chr) 5-133.3 Mbp (LOD 5.8), and chr5-54.2 Mbp (LOD 4.8), and two QTLs with significant linkage for TC: on chromosome 8, chr8-60.4 Mbp (LOD 3.8), and chromosome 2, chr2-243.5 Mbp (LOD 3.4). A QTL for LDL with significant linkage is detected on chromosome 5, chr5-104 Mbp (LOD 3.7). These QTLs contribute from 7% to 12% of total trait variance, respectively, with Dahl-S allele effects resulting in increased TC and LDL levels consistent with hyperlipidemia susceptibility in the parental Dahl-S rat strain. Predicted QTL-peaks do not coincide with previous genome scans. Human homologues of two TC-QTLs span genes listed in a LocusLink profile for cholesterol. Only suggestive loci were detected for HDL and total triglyceride levels. Altogether, the data demonstrates the contribution of multiple QTLs to hypercholesterolemia making a multipathway pathogenic framework imperative. QTL-peak candidate genes delineated are syntenic between rat and human genomes, increasing clinical relevance and mandating further study.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SR/HsdRatHypercholesterolemia MODEL: controlIAGP compared to SS/HsdRGD 
SS/HsdRatHypercholesterolemia MODEL: spontaneousIAGP compared to SR/HsdRGD 
Scl14RatHypercholesterolemia  IDA  RGD 
Scl15RatHypercholesterolemia  IDA  RGD 
Scl16RatHypercholesterolemia  IDA  RGD 
Scl17RatHypercholesterolemia  IDA  RGD 
Scl18RatHypercholesterolemia  IDA  RGD 
SR/HsdRatHypertriglyceridemia MODEL: controlIAGP compared to SS/HsdRGD 
SS/HsdRatHypertriglyceridemia MODEL: spontaneousIAGP compared to SR/HsdRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Scl14  (Serum cholesterol level QTL 14)
Scl15  (Serum cholesterol level QTL 15)
Scl16  (Serum cholesterol level QTL 16)
Scl17  (Serum cholesterol level QTL 17)
Scl18  (Serum cholesterol level QTL 18)

SR/Hsd  (NA)
SS/Hsd  (NA)

Additional Information