Articles in 2008

Joel Hirschhorn and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Gudmar Thorleifsson and colleagues.

Gudmar Thorleifsson and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Joel Hirschhorn and colleagues.

Sekar Kathiresan et al. report genome-wide association studies for polygenic dyslipidemia. From a meta-analysis of seven genome-wide association studies and follow-up in five replication studies, they identify 11 new genetic associations for LDL cholesterol, HDL cholesterol and triglycerides.

Nelson Freimer and colleagues report the first genome-wide association study of a longitudinal birth cohort (the Northern Finland Birth Cohort 1966). The results include new associations for nine quantitative metabolic traits.

Leena Peltonen and colleagues report a genome-wide association study of cholesterol and triglyceride levels in 16 population-based cohorts across Europe. Six new loci were identified, and overall a genetic risk score improves the screening of high risk groups for dyslipidemia.

Owen Sansom and colleagues show that conditional deletion of Pten specifically from the small intestinal epithelium in mice does not disrupt normal tissue architecture, but in the context of Apc deficiency leads to rapid development of adenocarcinoma. These findings suggest that Pten does not serve a rate-limiting, intrinsic role in regulating normal intestinal stem cell physiology.

Richard Houlston and colleagues identify four new susceptibility loci for colorectal cancer through a meta-analysis of genome-wide association data, followed by replication testing in a large collection of independent samples. The study brings to ten the number of confirmed loci harboring low-penetrance risk alleles for this common malignancy.

Sudipto Roy and colleagues report that zebrafish homologs of the transcription factor Foxj1 are sufficient to induce the motile ciliogenic program by upregulating expression of genes encoding key components of the motile ciliary machinery. Similar findings are reported in a related study by Chris Kintner and colleagues.

Chris Kintner and colleagues report that a Xenopus homolog of the transcription factor Foxj1 is sufficient to induce motile cilia by upregulating expression of genes encoding key components of the motile ciliary machinery. Similar findings are reported in a related study by Sudipto Roy and colleagues.

Jason Johnson and colleagues present the first genome-scale compendium of human alternative splicing events in 48 tissues. These data constitute a rich resource for the study of splicing in the human genome and its impact on development, physiology and disease.

Erin O'Shea and colleagues present a quantitative model of the Hog1 MAPK-dependent osmotic stress response in budding yeast derived from gene expression analyses in single- and multiple-mutant strains. The network reveals interactions involved in signal integration and processing and could serve as model for investigations into other gene regulatory networks.

Rune Toftgård and colleagues report that Lgr5, a G protein-coupled receptor recently identified as a marker of intestinal stem cells, marks a population of hair follicle stem cells that is actively proliferating and able to give rise to all cell types in the mouse hair follicle.

Ralf Sommer and colleagues present a draft genome sequence of the nematode Pristionchus pacificus, a species that lives in association with beetles and shows a major expansion of protein-coding genes. Comparative analysis with the genomes of the ecologically distinct nematodes C. elegans and B. malayi suggests insights into the association between their genome structures and differing lifestyles.

Cheryl Winkler and colleagues use admixture mapping to identify risk variants in MYH9 associated with focal segmental glomerulosclerosis and end-stage renal disease in African Americans. The risk variants are more common in populations with West African ancestry and contribute to the excess burden of end-stage kidney diseases in these populations. A similar finding is reported in an accompanying paper by Linda Kao and colleagues.

Linda Kao and colleagues use admixture mapping to identify risk variants in MYH9 associated with nondiabetic end-stage renal disease in African Americans. The risk variants are more common in populations with West African ancestry and contribute to the excess burden of end-stage kidney diseases in these populations. A similar finding is reported in an accompanying paper by Cheryl Winkler and colleagues.

David Altshuler and colleagues report the design of a hybrid SNP-CNV genotyping array (Affymetrix SNP 6.0 Array) allowing for integrated SNP and CNV detection. They describe its application to 270 HapMap samples to compile a high-resolution map of over 1,500 copy number polymorphisms, and related population-genetic analyses.

Augustine Kong and colleagues describe an approach for phasing SNPs into long haplotypes spanning multiple blocks of linkage disequilibrium. The method, termed long-range phasing, can be also used to impute long haplotypes for ungenotyped individuals.

Evan Eichler and colleagues present a sequence assembly of the inverted H2 haplotype of human chromosome 17q21.31 and show that the inversion is polymorphic in other great ape species. Their analyses suggest that the H2 configuration represents the ancestral state in great apes and that inversions have occurred independently in the human and chimpanzee lineages.

Peter Gallant and colleagues show that the control of endoreplication and cell competition in Drosophila are activities of Myc proto-oncogene in vivo that do not require the association with its Max binding partner. Further, a Myc derivative that does not interact with Max retains substantial biological activity, and Myc can control RNA polymerase III independently of Max.

Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. Kathryn Holt and colleagues now compare whole-genome sequences of 19 Typhi isolates dispersed throughout the phylogenetic tree of this pathogen, revealing notably little evidence of purifying selection, antigenic variation or recombination between isolates.