GENES AND DISEASE: Genome-association Study Links DNA Variants to MS
A large-scale genomic study has uncovered new genetic variations associated with multiple sclerosis (MS). The study, published in the August 30 edition of The New England Journal of Medicine, is the most comprehensive analysis of the genetic basis of MS to date. David Hafler helped to lead a large consortium of investigators at several universities and medical centers, including HMS, the Broad Institute, and Brigham and Women’s Hospital. Although the genes account for just a small amount of individual risk, they point to molecular pathways that may underlie the disease and be potential targets for treatment.

CELLULAR TRAFFICKING: Molecular Regulator Found for Iron Balance, Immune Response
The protein produced by a newly found gene has emerged in mice as a key regulator of the critical systems for iron balance and immunity. Clockwise from left, Fudi Wang, Nancy Andrews, Kristina Roberts, and colleagues used a variety of genetic approaches to reveal that the gene, Mon1a, which also exists in humans, is essential for the secretion of a variety of molecules from cells. The findings, in the August Nature Genetics, indicate that Mon1a is a commonly shared component of the secretory machinery.

EPIGENETICS: Genetics Reaches Past DNA and Its Molecular Packaging
Among researchers these days, there’s a buzz about epigenetics, a word many employ to describe inherited patterns of gene expression not directly reflected in the DNA sequence. One persistent mystery is how the cells in our body can share identical DNA, yet be as different as skin and bones—and pass on those traits when dividing. Many scientists are looking for answers in studies of chromatin, which packages active and inactive genes. But beware: a backlash is brewing because some scientists take umbrage at loose use of the term epigenetics, especially when invoked in connection with chromatin modifications. Clockwise from top left, Robert Kingston, Kevin Struhl, Danesh Moazed, Stephen Buratowski, Yang Shi, Bradley Bernstein, Jeannie Lee, and Ting Wu weigh in.

GENETIC INFORMATION: Zero Discovered in Code Controlling Gene Expression
HMS researchers Yang Shi (left) and Fei Lan have discovered a whole new cipher to the histone code. It appears that not only the presence but also the absence of chemical groups on histone tails can act as markers that may influence gene expression. They found that BHC80, a protein component of the histone demethylase enzyme LSD1, only recognizes the unmethylated histone H3 lysine 4 (H3K4). Shi believes that the protein acts as a place holder for LSD1, keeping other enzymes from remethylating the histone and changing the chromatin state. Their study appears in the Aug. 9 Nature.

GENETIC SELECTION: Evolution Uncovers Gems Amid Noncoding Barrens
Scattered through the vast regions of DNA that do not code for protein lie single nucleotides so nearly identical between human beings and other mammals that researchers have concluded they must have been acted on by natural selection to carry out a function. But bits of funtional genetic material in barren regions were thought to show up as continuous sequences of conserved DNA rather than as lone nucleotides. Saurabh Asthana (left), Shamil Sunyaev (right), and Gregory Kryukov, working with scientists at the University of Washington, report in the July 24 Proceedings of the National Academy of Sciences, that a large number of solitary noncoding nucleotides bore the stamp of natural selection, meaning that they essentially were unchanged among individuals. In fact, the overall number of conserved single nucleotides was greater than the number of conserved continuous sequences in the noncoding regions of their sample.