Mutant of the Month

Credit: Photo courtesy of Jon Meier

As cold weather grips the northern hemisphere, we offer, as our January MoM, a small tree that is most beguiling during the winter months: Corylus avellana contorta, also known as the corkscrew hazel. A naturally occurring mutant of wild hazel produces distorted shoots with a corkscrew appearance (also shown here are the catkins that bloom in late winter). The original mutant was discovered in Gloucestershire, England, in 1863. As the mutation is not in the germ line, every tree in cultivation can be traced back to the original by cutting or grafting. The corkscrew hazel is also occasionally called 'Harry Lauder's Walking Stick', after the famous Scottish music hall entertainer Harry Lauder, who carried a characteristic crooked cane. After his only son John was killed on a battlefield in France during the First World War, Lauder entertained the troops in his honor and raised funds for disabled Scottish veterans, ultimately earning a knighthood from King George V for service to his country. AP

Special genetics

On December 8, Rockefeller University hosted the Genomic Medicine Discussion Group, the latest in a series of symposia sponsored by the New York Academy of Sciences. The topic for the occasion was “Genetic Studies in Special Populations”. Harry Ostrer (NYU School of Medicine) introduced the meeting by defining a 'special' population as one with a small, discrete group of founders who migrated and have undergone an extended period of endogamy. Ostrer also described his work on the genetic profiling of Ashkenazi Jews, including recently published findings on the estimated timing of founder mutations in the Jewish diaspora. Jeff Friedman (Rockefeller University) outlined a long-term study of the people of Kosrae, a small Pacific island due east of the Philippines whose population underwent a severe bottleneck in the late 1800s after contact with westerners. The introduction of a western diet after the Second World War has led to increasing incidence of obesity, diabetes and hypertension, and a whole-genome association study is underway to identify risk variants. Erik Puffenberger (Clinic for Special Children) discussed his work with the Old Order Mennonites and Old Order Amish of Lancaster County, Pennsylvania, whose members have a high incidence of certain metabolic disorders but a notable absence of more common genetic diseases, such as cystic fibrosis. Finally, Kari Stefansson (deCODE Genetics) detailed his company's success in identifying variants that predispose to complex disease. He noted that risk haplotypes tend to affect gene expression, and he predicted that genes involved in complex disease would be those with the largest genetic component in the variance of gene expression. All told, the symposium highlighted the value of studying unique populations with a known history and reduced genetic diversity. AP

Epigenetic organization, epigenetic instability

At an AACR meeting on “Chromosomes, Chromatin and Cancer Epigenetics”, 10–14 November, 2004, in Waikoloa, Hawaii, organizers Peter Jones and Rudolph Jaenisch assembled a program that ranged from silencing of fission yeast centromeres to ongoing clinical trials with histone deacetylase inhibitors. The meeting sparked an important discussion among Peter Laird, Jean-Pierre Issa and Manuel Perucho as to whether the CpG island methylator phenotype in colorectal cancer (Proc. Natl. Acad. Sci. USA 96, 8681–8686; 1999) has been defined in a sufficiently unbiased way that it is possible to find an underlying cause. Most genes inactivated by DNA hypermethylation in cancers show age-dependent methylation in normal colon and in cancers (Cancer Cell 4, 121–131; 2003). But there is a distinct subset of genes that are methylated in a cancer-specific manner. This 'CIMP' phenotype can be thought of as a form of epigenetic instability affecting CpG islands, just as genetic mutator tumors have a mismatch-repair defect affecting microsatellites. Because epigenetic inactivation and genetic mutator processes can occur together, it is important to distinguish the mechanisms from one another and to distinguish epimutator from epimutations. For example, chance methylation of the wild-type mismatch-repair gene MLH1, with or without epigenetic silencing of other CIMP targets, may be a cause of sporadic microsatellite instability. As the New York traffic continues to worsen, this relatively accessible conference center in Waikoloa may give the Cold Spring Harbor meetings some serious competition. MA

Counting CROEs

I am indebted to Steve Mount for the information that what I had informally been calling the 'coding region of an exon' apparently has no name in the bioinformatics community working on genome annotation. This anonymity is unlikely to disturb geneticists but might create confusion when students or informatics researchers miss the distinction between an exon and the portion of the exon translated into protein. Here is a suggested convention: the portion of a 5′ exon from the initiator AUG to the first splice donor is a 5′ CROE and the region from the splice acceptor to the terminator codon is a 3′ CROE. I think these terms can readily be qualified to accommodate alternative splices. MA

Touching Base written by Myles Axton and Alan Packer