TABLE 1.
Mouse bioinformatic evidence for human GWA genes
| HDL QTL Crossa | Gene Expression Differencesb | Amino Acid Substitutionc | ||||||
|---|---|---|---|---|---|---|---|---|
| Gene | Strains | Diet | Sex | Fold Change(P) | Amino Acid | Charge/Polarity | Functional? | Conserved? |
| Known HDL gene | ||||||||
| Abca1 | D2xCAST | HF | M | +1.67(<0.001) | T251I | Polarity | No | No |
| V343M | No | No | No | |||||
| S658G | No | No | No | |||||
| I691V | No | No | Yes | |||||
| N1889T | No | No | Yes | |||||
| CASTx129 | HF | M | +1.56 (<0.001) | |||||
| PERAxI | HF | F | +1.15 (0.165) | S658G | No | No | No | |
| PERAxD2 | HF | F | +1.05 (0.542) | V1291I | No | No | No | |
| E1550K | Polarity and charge | Yes | Yes | |||||
| T1565N | No | No | No | |||||
| Unknown HDL gene | ||||||||
| Galnt2 | B6xCASAa | C | F | -1.27 (0.010) | None | — | — | — |
| Wwox | B6xCAST | C | F | −1.16 (0.342) | V186M | No | Yes (SIFT) | No |
| Cdh13 | B6xCAST | C | F | +1.16 (0.052) | N56S | No | No | No |
| Y214F | Polarity | Yes (SIFT) | Yes | |||||
| I660M | No | No | Yes | |||||
HF, high-fat diet; C, chow diet; M, male; F, female.
Bold indicates the high allele strain. CAST was used as a surrogate for CASA.
Gene expression differences between the QTL parental strains. All quantitative PCR performed regarding both loci are reported here. Quantitative PCR was performed on cDNA from liver samples from at least three mice for the most relevant strain/diet/sex. Quantitative PCR was performed for Abca1, Galnt2, and Wwox using β2 microglobulin as the endogenous control. The microarray result is indicated for Cdh13 (probe 1431824_at). The fold change is indicated as the gene expression of the high allele strain (bold) compared with the low allele strain.
For Cdh13, amino acid substitutions were determined using the high-density SNP component of the MPD database and the imputed SNPs from the CGD with a minimum confidence level of 0.9. For Galnt2 and Wwox, amino acid substitutions were determined by resequencing of B6 and CAST. Functionality was determined by using Polyphen and SIFT. Conservation was determined by comparison with mammals at the UCSC website. For Abca1, the amino acid substitutions are arranged in two groups: the crosses involving CAST and the crosses involving PERA. Additional information on the sequencing results is available in supplementary Table IX and XII.