Volume 41 Issue 2, February 2009

Obesity genetics is making progress, as evidenced by the recent discovery of 15 new loci associated with body mass index. The function of the likely candidate genes in associated regions suggests a key role for the hypothalamus in the genetics of weight control.

A new study identifies mutations in the HR gene as the cause of Marie Unna hereditary hypotrichosis (MUHH). The mutations seem to disrupt an unusual leader sequence–based mechanism of translational repression, making MUHH the first example of a disease linked to this form of repression.

Experimental reverse evolution, in which a population is readapted to an ancestral environment, can probe the nature and extent of evolutionary memory. A new study shows that standing genetic variation is key to this memory in experimental Drosophila populations, where selection drives rapid but incomplete convergence to ancestral genotypes.

An integrative genetical genomics study in Arabidopsis reports that six QTL hot spots have system-wide effects on a wide range of molecular and phenotypic traits, providing empirical evidence for phenotypic buffering.

Four teams of analysts attempted exact reproduction of results of 18 microarray experiments published in the journal in 2005–2006 using the data and analytical methods detailed in the original publications. In addition to MIAME criteria, the authors recommend publication of an explicit record of the analytical protocols used.

Philippe Froguel and colleauges present a genome-wide association study for early-onset and morbid adult obesity, reporting three new genetic associations to obesity.

Thomas Sander and colleagues identify 15q13.3 microdeletions in 1% of individuals with idiopathic generalized epilepsy (IGE). The majority of these individuals do not show intellectual disability, schizophrenia or other neuropsychiatric phenotypes, thus extending the phenotypic spectrum associated with 15q13.3 microdeletions.

Matthew Farrer and colleagues report missense mutations in DCTN1, encoding dynactin, in eight families with Perry syndrome, a neurodegenerative disorder marked by early-onset parkinsonism, depression, severe weight loss and hypoventilation.

Ritsert Jansen and colleagues present an integrative analysis for genome-wide variation in transcript, protein and metabolite abundance in Arabidopsis, reporting six QTL hot spots with system-wide effects.

James Lupski, Orly Reiner and colleagues report seven individuals with submicroscopic copy number gains in the 17p13.3 region, supported by additional studies in transgenic mice. Duplications overlapping PAFAH1B1 (encoding LIS1) were associated with mild brain structural abnormalities, moderate to severe developmental delay and failure to thrive.

Andy Feinberg and colleagues show in a colon cancer model that most DNA methylation alterations occur in sequence regions distinct from promoters or canonical CpG islands, termed 'CpG island shores', and that this methylation is strongly related to gene expression and can discriminate tissue types regardless of species of origin.

Kumarasamy Thangaraj and colleagues describe the association of a 25-bp deletion in MYBPC3 with heritable cardiomyopathies in Indian populations. They find a high prevalence (4–8%) of the deletion in surveyed Indian populations and an absence of the deletion in surveyed populations outside of Southeast Asia.

Steve Younkin and colleagues report the results of a genome-wide association study for late-onset Alzheimer's disease. A variant on the X chromosome in PCDH11X is associated with increased risk of the disorder. PCDH11X encodes a protocadherin and is a member of a cell surface receptor molecule family.

The Collaborative Association Study of Psoriasis, in partnership with the Genetic Association Information Network (GAIN), reports a genome-wide association study for psoriasis. They identify new replicated associations that highlight a role for the IL-23 and NF-κB pathways in psoriasis susceptibility.

Xuejun Zhang and colleagues report a genome-wide association and replication studies for psoriasis, conducted in Chinese populations. They confirm previous associations in MHC and IL12B to psoriasis susceptibility, and report a new association within the LCE gene cluster at 1q21.

Xavier Estivill and colleagues report that deletion of the late cornified envelope LCE3C and LCE3B genes increases susceptibility to psoriasis, possibly through compromised skin barrier function.

Richard Duerr and colleagues present a genome-wide association study of ulcerative colitis. They identify new risk loci on chromosomes 1p36 and 12q15.

Following a replicated genome-wide association study for basal cell carcinoma, Thorunn Rafnar and Patrick Sulem and colleagues have identified a locus associated with multiple cancers that contains the telomerase reverse transcriptase gene TERT and the CLPTM1L gene implicated in cisplatin-induced apoptosis.

Xue Zhang and colleagues report mutations in an inhibitory upstream open reading frame flanking the human hairless gene in individuals with Marie Unna hereditary hypotrichosis. These mutations result in increased translation of the main physiological hairless ORF, suggesting that fine-tuning of hairless protein levels is important in the control of hair growth.

Frank Rutsch and colleagues show that the cblF inborn error of vitamin B₁₂ metabolism, which is characterized by accumulation of free vitamin B₁₂ in lysosomes, is caused by mutations in the gene encoding the lysosomal membrane protein LMBD1. These findings suggest a critical function for LMBD1 in exporting cobalamin from lysosomes.

Arturas Petronis and colleagues present the first genome-wide study of interindividual differences in DNA methylation through genome-scale DNA methylation profiling in tissues from monozygotic and dizygotic twins. The data showed that dizygotic co-twins have higher degrees of epigenetic differences than monozygotic co-twins, which the authors attribute at least partially to epigenetic, as opposed to genetic, differences in the zygotes.

Andrew Feinberg and colleagues identify large chromatin domains marked by histone H3 lysine 9 dimethylation in human and mouse cells. These blocks show tissue specificity, and their appearance is correlated with differentiation status.

Henrique Teotónio and colleagues report a comprehensive study of the molecular population genetics of adaptation and reverse evolution in Drosophila. They conclude that adaptive reverse evolution in this context tends to occur from the sorting and recombination of standing genetic variation at multiple loci, rather than from the fixation of new mutations.

Timothy Nelson and colleagues present a transcriptome atlas of 40 key cell types from rice (Oryza sativa). The atlas reveals previously unrecognized cellular properties, and should serve as an essential resource for functional genomic analyses of rice and other plants.