Table 3. Haplotype analysis of Aath4 on Chr 2.
| Gene | Mb | Haplotype | Aortic expression | Macrophage expression | AA substitution | Human mutation, GWAS (-log10P) | KO / mutant mouse phenotype | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| DBA/129 | B6/129 | Level | DBA/129 | B6/129 | Level | ||||||
| Fbn1 | 125.1 | 129, B6 ≠ DBA, C3H | 1.1 | 1.5 | 1684 | 0.9 | 0.2 | 127 | A427V, D492N | Cholesterol (10.0), Aortic aneurysm (12.2) | Right ventricle dilation |
| Eid1 | 125.5 | 129, B6 ≠ DBA, C3H | 1.8 a | 1.3 | 125 | 1.4 | 1.2 | 59 | apoE level (8.4) | ||
| Dtwd1 | 126.0 | 129, B6 ≠ DBA, C3H | 1.1 | 0.9 | 158 | 1.1 | 0.9 | 170 | S25P, T28A, E33G, D117N, E184K | Antidepressant effect (6.3) | |
| Hdc | 126.4 | 129, B6 ≠ DBA, C3H | 0.9 | 0.9 | 24 | 0.6 | 0.3 | 53 | K177T | Stroke (3.9) | Abnormal mast cell morphology, Decreased plaques in Hdc -/- Apoe -/- mice |
| Bcl2l11 | 128.0 | 129, B6 ≠ DBA, C3H | 0.7 | 0.8 | 62 | 0.8 | 2.0 | 262 | CAD (4.2), Monocytes(6.4) | Vasculitis, Increased lymphocytes | |
| Mertk | 128.5 | 129, B6 ≠ DBA, C3H | 1.0 | 1.4 a | 784 | 0.8 | 1.7 | 782 | W25G, T80E, S479R and 6 others | Retinitis pigmentosa Stroke (3.3) | Abnormal retinal vascular morphology, Impaired platelet aggregation, Increased necrosis in Mertk KD Apoe -/- plaques |
| Adam33 | 130.9 | 129, B6, C3H ≠ DBA | 0.8 | 1.1 | 176 | 0.7 | 2.7 | 47 | K85N, T409V, R466K | BP (4.1) | Normal phenotype |
| Siglec1 | 130.9 | 129, B6, C3H ≠ DBA | 1.5 | 1.4 | 47 | 0.6 | 2.2 | 787 | R162G, and 6 others | Abnormal B cell number | |
| Adra1d | 131.4 | 129, B6, C3H ≠ DBA | 1.3 | 1.1 | 755 | 1.0 | 1.4 | 16 | A472V | Uric acid (7.1), Respiratory function (6.5) | Hypotension |
| Plcb4 | 135.5 | 129, B6, C3H ≠ DBA | 1.0 | 0.9 | 1671 | 0.8 | 0.3 | 101 | BW (5.7), Medial thickness (4.2), Leukocyte counts (9.5), HDL (4.2) | Hypoactive, Impaired coordination | |
| Kif16b | 142.4 | 129, B6, C3H ≠ DBA | 0.8 | 1.0 | 351 | 1.0 | 1.2 | 436 | Q759L, F825Y, D929G, T937N, A1005V, C1019R | Glucose(6) | Embryonic lethality, Absence of epiblast |
| Pcsk2 | 143.4 | 129, B6, C3H ≠ DBA | 1.3 | 1.1 | 13 | 1.0 | 1.0 | 12 | Carotid artery (4.5), Menarche (7.5) | Impaired processing of neuroendocrine hormones, Hypertension | |
| Thbd | 148.2 | 129, B6, C3H ≠ DBA | 0.8 | 1.1 | 1110 | 1.0 | 1.0 | 257 | Osteoporosis (12.5) | Abnormal leukocyte adhesion, Increased MI size | |
| Cd93 | 148.3 | 129, B6, C3H ≠ DBA | 1.1 | 1.2 | 489 | 0.9 | 1.3 | 1667 | N264H | Impaired macrophage phagocytosis | |
| Cst3 | 148.7 | 129, B6 ≠ DBA, C3H | 1.2 a | 1.0 | 3987 | 1.2 | 1.0 | 3759 | Kidney disease (137.7) | Thinning of tunica media and increased SM cell in atherosclerotic plaques in Cst3 -/- ;Apoe -/- mice | |
Genes with DBA-unique sequences (DBA ≠ B6, 129) within and near the interval of 123–148 Mb are shown. For each gene, expression ratios in the aorta and macrophages, expression levels in 129, amino acid (AA) differences (B6, 129-position-DBA), associations with atherosclerosis indicated by GWAS data, and phenotypes of knockout or mutant mice are shown. Ratios between two strains that show significant difference in the expression are bolded. AA substitutions that are predicted to be deleterious by SIFT program are bolded (see S5 Table).
a P < 0.05.