Background -Optimal nutritional choices are linked with better health but many current

High-precision genetic mapping was used to define the regions that contain centromere functions on each natural chromosome in Arabidopsis thaliana. These regions exhibited dramatic recombinational repression and contained complex DNA surrounding large arrays of 180-base pair repeats. Unexpectedly, the DNA within the centromeres was not merely structural but also encoded several expressed genes. The regions flanking the centromeres were densely populated by repetitive elements yet experienced normal levels of recombination. The genetically defined centromeres were well conserved among Arabidopsis ecotypes but displayed limited sequence homology between different chromosomes, excluding repetitive DNA. This investigation provides a platform for dissecting the role of individual sequences in centromeres in higher eukaryotes.

Flowering plants display a remarkable range of inflorescence architecture, and pedicel characteristics are one of the key contributors to this diversity. However, very little is known about the genes or the pathways that regulate pedicel development. The brevipedicellus (bp) mutant of Arabidopsis thaliana displays a unique phenotype with defects in pedicel development causing downward-pointing flowers and a compact inflorescence architecture. Cloning and molecular analysis of two independent mutant alleles revealed that BP encodes the homeodomain protein KNAT1, a member of the KNOX family. bp-1 is a null allele with deletion of the entire locus, whereas bp-2 has a point mutation that is predicted to result in a truncated protein. In both bp alleles, the pedicels and internodes were compact because of fewer cell divisions; in addition, defects in epidermal and cortical cell differentiation and elongation were found in the affected regions. The downward-pointing pedicels were produced by an asymmetric effect of the bp mutation on the abaxial vs. adaxial sides. Cell differentiation, elongation, and growth were affected more severely on the abaxial than adaxial side, causing the change in the pedicel growth angle. In addition, bp plants displayed defects in cell differentiation and radial growth of the style. Our results show that BP plays a key regulatory role in defining important aspects of the growth and cell differentiation of the inflorescence stem, pedicel, and style in Arabidopsis.

OBJECTIVE-Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry and to finemap across the associated genomic interval.RESEARCH DESIGN AND METHODS-We performed association studies in 12 independent cohorts comprising Ͼ45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the ϳ417-kb region of linkage disequilibrium spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval.RESULTS-We provide comprehensive evidence that GCKR rs780094 is associated with opposite effects on fasting plasma triglyceride (P meta ϭ 3 ϫ 10 Ϫ56) and glucose (P meta ϭ 1 ϫ 10 Ϫ13 ) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P ϭ 5 ϫ 10 Ϫ5). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r 2 ϭ 0.93 with rs780094) as the strongest association signal in the region.CONCLUSIONS-These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism. Diabetes 57:3112-3121, 2008

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

The genomes of higher plants and animals are highly differentiated, and are composed of a relatively small number of genes and a large fraction of repetitive DNA. The bulk of this repetitive DNA constitutes transposable, and especially retrotransposable, elements. It has been hypothesized that most of these elements are heavily methylated relative to genes, but the evidence for this is controversial. We show here that repeat sequences in maize are largely excluded from genomic shotgun libraries by the selection of an appropriate host strain because of their sensitivity to bacterial restriction-modification systems. In contrast, unmethylated genic regions are preserved in these genetically filtered libraries if the insert size is less than the average size of genes. The representation of unique maize sequences not found in plant reference genomes is also greatly enriched. This demonstrates that repeats, and not genes, are the primary targets of methylation in maize. The use of restrictive libraries in genome shotgun sequencing in plant genomes should allow significant representation of genes, reducing the number of reactions required.

Several polymorphisms in the APOA5 gene have been associated with increased plasma triglyceride (TG) concentrations. However, associations between APOA5 and lipoprotein subclasses, remnant-like particles (RLPs), and cardiovascular disease (CVD) risk have been less explored. We investigated associations of five APOA5 single-nucleotide polymorphisms (SNPs; ؊ 1131T Ͼ C, ؊ 3A Ͼ G, 56C Ͼ G IVS3 ؉ 476G Ͼ A, and 1259T Ͼ C) with lipoprotein subfractions and CVD risk in 1,129 men and 1,262 women participating in the Framingham Heart Study. Except for the 56C Ͼ G SNP, the other SNPs were in significant linkage disequilibria, resulting in three haplotypes (11111, 22122, and 11211) representing 98% of the population. SNP analyses revealed that the ؊ 1131T Ͼ C and 56C Ͼ G SNPs were significantly associated with higher plasma TG concentrations in both men and women. For RLP and lipoprotein subclasses, we observed gender-specific association for the ؊ 1131T Ͼ C and 56C Ͼ G SNPs. Female carriers of the ؊ 1131C allele had higher RLP concentrations, whereas in males, significant associations for RLPs were observed for the 56G allele. Moreover, haplotype analyses confirmed these findings and revealed that the 22122 and 11211 haplotypes exhibited different associations with HDL cholesterol concentrations.In women, the ؊ 1131C allele was associated with a higher hazard ratio for CVD (1.85; 95% confidence interval, 1.03 ؊ 3.34; P ‫؍‬ 0.04), in agreement with the association of this SNP with higher RLPs. Increased plasma triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and reduced high density lipoprotein cholesterol (HDL-C) concentrations are widely accepted as cardiovascular disease (CVD) risk factors (1-3). Their plasma concentrations are regulated by a combination of genetic and nongenetic factors. Whereas much emphasis has been placed on the identification of factors modifying the cholesterol fraction of lipoproteins, less weight has been placed on elucidating modifiers of TG concentrations. LPL has been traditionally considered as the major enzyme involved in plasma TG regulation (4). However, most of the genetic variability for plasma TG concentrations in the general population still remains unexplained. Therefore, other loci need to be identified to account for the bulk of the genetic variability corresponding to this phenotype. Recently, apolipoprotein A-V (apoA-V) has emerged as a significant player in plasma TG metabolism, as shown in several experimental animal models (5-8) and in human primary cell cultures (9). The evidence from mouse models consistently supports the role of apoA-V as an activator of LPL, thus increasing lipolysis and VLDL clearance (7,8). More recent evidence from a double-knockout mouse model supports the notion that the apoA-V ( APOA5 ) and apoC-III ( APOC3 ) genes independently influence plasma TG concentrations but in an opposing manner (10). However, less agreement exists regarding the potential effect of apoA-V in VLDL synthesis (7,8). Another line of evidence for the relev...

CLOCK polymorphisms interact with FAs to modulate MetS traits. The dietary source and membrane content of MUFAs are implicated in the relations between alterations in the circadian system and MetS.