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721.
Christiane L. Haase Ruth Frikke-Schmidt B?rge G. Nordestgaard Anne Tybj?rg-Hansen 《PLoS genetics》2012,8(11)
Rare genetic variants, identified by in-detail resequencing of loci, may contribute to complex traits. We used the apolipoprotein A-I gene (APOA1), a major high-density lipoprotein (HDL) gene, and population-based resequencing to determine the spectrum of genetic variants, the phenotypic characteristics of these variants, and how these results compared with results based on resequencing only the extremes of the apolipoprotein A-I (apoA-I) distribution. First, we resequenced APOA1 in 10,330 population-based participants in the Copenhagen City Heart Study. The spectrum and distribution of genetic variants was determined as a function of the number of individuals resequenced. Second, apoA-I and HDL cholesterol phenotypes were determined for nonsynonymous (NS) and synonymous (S) variants and were validated in the Copenhagen General Population Study (n = 45,239). Third, observed phenotypes were compared with those predicted using an extreme phenotype approach based on the apoA-I distribution. Our results are as follows: First, population-based resequencing of APOA1 identified 40 variants of which only 7 (18%) had minor allele frequencies >1%, and most were exceedingly rare. Second, 0.27% of individuals in the general population were heterozygous for NS variants which were associated with substantial reductions in apoA-I (up to 39 mg/dL) and/or HDL cholesterol (up to 0.9 mmol/L) and, surprisingly, 0.41% were heterozygous for variants predisposing to amyloidosis. NS variants associated with a hazard ratio of 1.72 (1.09–2.70) for myocardial infarction (MI), largely driven by A164S, a variant not associated with apoA-I or HDL cholesterol levels. Third, using the extreme apoA-I phenotype approach, NS variants correctly predicted the apoA-I phenotype observed in the population-based resequencing. However, using the extreme approach, between 79% (screening 0–1st percentile) and 21% (screening 0–20th percentile) of all variants were not identified; among these were variants previously associated with amyloidosis. Population-based resequencing of APOA1 identified a majority of rare NS variants associated with reduced apoA-1 and HDL cholesterol levels and/or predisposing to amyloidosis. In addition, NS variants associated with increased risk of MI. 相似文献
722.
Propionyl-coenzyme A carboxylase of Mycobacterium smegmatis. An electron microscopic study 总被引:3,自引:0,他引:3
Propionyl-CoA carboxylase has been purified to homogeneity and examined in electron microscope. The native carboxylase presents a profile with a large central subunit to which smaller subunits are attached. The central subunit has two prominent profiles, one circular (100 A) with a central hole and the other rectangular (70 X 100 A). The six polypeptides of this subunit appear to be arranged in a cylindrical structure. Six spherical (50 A) biotin-containing peripheral subunits are attached in sets of three to the two opposite circular faces of the central subunit. A model of the 18-S carboxylase is presented. 相似文献
723.
Possible speciation with gene flow in tropical cave snails 总被引:1,自引:0,他引:1
M. Schilthuizen A. S. Cabanban M. Haase 《Journal of Zoological Systematics and Evolutionary Research》2005,43(2):133-138
In this paper, we present a newly-discovered troglobitic species of the snail genus Georissa from a limestone cave in Borneo. Molecular phylogenetic analysis of 16S mitochondrial DNA sequences shows that its ancestor is the local epigean population of Georissa saulae , living in the rainforest directly at the cave entrances. A multivariate analysis of shell characters reveals that the troglobite has diverged morphologically, but is connected to its epigean ancestor by a population of intermediate morphology in the twilight zone of the cave. The molecular data further indicate ongoing gene flow between the epigean population and the troglobite, via the intermediate population. We suggest that the troglobite may have diverged from its ancestor without prior isolation. 相似文献