Genetic variation in the DNA of mitochondria – the “power plants” of cells – contributes to a person’s risk of developing age-related macular degeneration (AMD), Vanderbilt investigators report May 7 in the journal PLoS ONE.

The study is the first to examine the mitochondrial genome for changes associated with AMD, the leading cause of blindness in Caucasians over age 50.

“Most people don’t realize that we have two genomes,” said lead author Jeff Canter, M.D., M.P.H., an investigator in the Center for Human Genetics Research. “We have the nuclear genome – the “human genome” – that makes the cover of all the magazines, and then we also have this tiny genome in mitochondria in every cell.” … Continue Reading »

Much work has been done to identify genetic variations that predispose women to breast cancer. Previous work showed that variants in the gene called fibroblast growth factor receptor 2 (FGFR2) were associated with increased risk of the disease, but how these variants translated into increased risk was unknown. A new paper by Kerstin Meyer and colleagues, published this week in the open-access journal PLoS Biology, shows how specific changes in the FGFR2 gene alter the way regulatory molecules bind to it, leading to increased gene expression, which, in turn, increases the risk of developing breast cancer.

By comparing all of the tiny differences in the genomes of people with breast cancer to those in a control population, FGFR2 had been flagged up as a region of the genome that is consistently different between the two groups. FGFR2 encodes a protein that sits in the membrane of cells and works in a signalling pathway important for cell growth.

This study, conducted in the Cancer Research UK Cambridge Research Institute, has identified just what these slight genetic changes mean at the molecular level. FGFR2 genes altered at two specific points have a greater affinity for binding certain transcription factors—regulatory proteins that influence gene expression patterns. Because of this additional binding, more FGFR2 protein is produced in cells carrying the mutation and this seems to be enough to increase the risk of cancer a small but significant amount.

Interestingly, the mutation occurs not in the coding regions of the genes (the bits translated into protein by cellular machinery), but rather, in an intron (a region of DNA found amongst the coding bits). The two alterations therefore affect the regulation of the gene, but the proteins produced are normal; there is too much of it for the cells to develop as normal, instead becoming cancerous.

Meyer KB, Maia A-T, O’Reilly M, Teschendorff AE, Chin S-F, et al. (2008) Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLoS Biol 6(5):e108. doi:10.1371/journal.pbio.0060108

Source: Public Library of Science

A 2001/2002 report by the World Health Organization found that, among young people in western countries who began drinking before 16 years of age, the average age of initiation was 12 years of age. A new twins study from the Netherlands has found that genetic factors appear to be involved in the early initiation of alcohol use, while common environmental factors become involved once alcohol use has begun.

Results will be published in the June issue of Alcoholism: Clinical & Experimental Research and are currently available at OnlineEarly.

“A lot of studies examining alcohol use in adolescents have focused on several social factors in alcohol use, for example, the influence of friends and parents,” said Evelien A. P. Poelen, a researcher at Radboud University Nijmegen, “while genetic factors have often been neglected. We thought both factors should be taken into account simultaneously in order to examine the relative contribution of both to the initiation and frequency of drinking.” … Continue Reading »

A research on the bone health of one of the oldest persons in the world, who recently died at the age of 114, reveals that there were no genetic modifications which could have contributed to this longevity. The research team, directed by Universitat Autònoma de Barcelona professor Adolfo Díez Pérez, pointed out a healthy lifestyle, a Mediterranean diet, a temperate climate and regular physical activity as the reasons for his excellent health.

The research team studied the bone mass and analyzed the genetics of a man with enviable health who at the time of the study was 113 years old. The research was carried out with four other members of his family: a 101-year-old brother, two daughters aged 81 and 77, and a nephew aged 85, all of them born and still living in a small town of the island of Menorca. The research findings were recently published in the Journal of Gerontology and reported that the man’s bones were in excellent conditions: his bone mass was normal, there were no anomalous curvatures and he had never sustained a fracture.

With regard to the genetical analyses, researchers were unsuccessful in finding any mutations in the KLOTHO gene, which is generally related to a good level of mineral density and therefore healthy bones. Neither did they find any mutations in the LRP5 gene, which is associated with longevity. None of the members of the family who participated in the study presented any mutations in this gene.

The results of the research do not rule out the possibility that other genetic mutations could positively influence longevity. However, researchers do point out the fact that the excellent health of this family, and of the 113-year-old man in particular, is probably due to a Mediterranean diet, the temperate climate of the island, a lack of stress and regular physical activity. The article underlines the fact that until the age of 102, the man cycled every day and looked after the family orchard.

Source: Universitat Autonoma de Barcelona

Enzymes regulating genetic expression can be just as important as the genome itself, increasing evidence shows. The expanding field of epigenetics focuses on the multiple influences on DNA and surrounding molecules that determine whether genes are turned on or off during development and disease processes.

A consortium of scientists, led by Albert Jeltsch at Jacobs University, Breman, Germany, Yoichi Shinkai at Kyoto University, Japan, and Xiaodong Cheng at Emory University, has now discovered new non-histone targets for one enzyme previously believed to modify only histones–the group of proteins that creates tightly bundled packages of DNA strands. The research is reported online in the journal Nature Chemical Biology. … Continue Reading »

The Centre for Addiction and Mental Health (CAMH) has discovered a new form of intellectual disability involving mental retardation (MR) along with the eye defect retinitis pigmentosa (RP). CAMH also discovered the previously unidentified gene that causes this disorder, CC2D2A. This scientific advance will help understand the developmental and biological processes involved in brain development, and may help identify ways to diagnose and treat intellectual disabilities.

Under the direction of Dr. John Vincent, scientist at CAMH, the team identified a mutation in CC2D2A that causes the production of a shortened protein missing the C2, or calcium-binding, domain. This protein mutation results in faulty cell function, which leads to MR with RP. … Continue Reading »

About 40 percent of African-Americans have a genetic variant that can protect them after heart failure and prolong their lives, according to research conducted at Washington University School of Medicine in St. Louis and collaborating institutions.

The genetic variant has an effect that resembles that of beta blockers, drugs widely prescribed for heart failure. The new study offers a reason why beta blockers don’t appear to benefit some African-Americans. … Continue Reading »

A gene mutation responsible for the most common form of inherited colon cancer is older and more common than formerly believed, according to a recent study.

The findings provide a better understanding of the spread and prevalence of the American Founder Mutation, a common cause in North America of Lynch syndrome, a hereditary cancer syndrome that greatly increases a person’s risk for developing cancers of the colon, uterus and ovaries.

The same investigators discovered the mutation in 2003. That research identified nine families with the mutation and concluded that a German immigrant couple brought the mutation to North America in 1727. … Continue Reading »