ABCA1 p.Glu1550Lys
| Predicted by SNAP2: | A: N (57%), C: N (53%), D: N (53%), F: D (66%), G: D (66%), H: N (57%), I: D (66%), K: D (63%), L: D (66%), M: D (59%), N: N (53%), P: D (75%), Q: N (66%), R: D (63%), S: N (53%), T: N (57%), V: D (66%), W: D (75%), Y: D (66%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: N, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: N, S: N, T: N, V: N, W: D, Y: D, |
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[hide] The mouse QTL map helps interpret human genome-wid... J Lipid Res. 2011 Jun;52(6):1139-49. Epub 2011 Mar 28. Leduc MS, Lyons M, Darvishi K, Walsh K, Sheehan S, Amend S, Cox A, Orho-Melander M, Kathiresan S, Paigen B, Korstanje R
The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol.
J Lipid Res. 2011 Jun;52(6):1139-49. Epub 2011 Mar 28., [PMID:21444760]
Abstract [show]
Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies.
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No. Sentence Comment
84 For PERA crosses, we identified eight polymorphisms that changed amino acids between PERA and the strains I and D2; one of these, E1550K, was damaging according to Polyphen (Table 1 and supplementary Table IX).
X
ABCA1 p.Glu1550Lys 21444760:84:130
status: NEW162 E1550K was predicted to be damaging.
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ABCA1 p.Glu1550Lys 21444760:162:0
status: NEW198 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. a Bold indicates the high allele strain.
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ABCA1 p.Glu1550Lys 21444760:198:245
status: NEW82 For PERA crosses, we identified eight polymorphisms that changed amino acids between PERA and the strains I and D2; one of these, E1550K, was damaging according to Polyphen (Table 1 and supplementary Table IX).
X
ABCA1 p.Glu1550Lys 21444760:82:130
status: NEW160 E1550K was predicted to be damaging.
X
ABCA1 p.Glu1550Lys 21444760:160:0
status: NEW196 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 afa;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. a Bold indicates the high allele strain.
X
ABCA1 p.Glu1550Lys 21444760:196:245
status: NEW