New resveratrol study in Mus musculus

Mouse Au Vin @ www.newyorker.com

To sprint or not

Atlas Sports Genetics is a company in Boulder Colorado that will test test your child's DNA and send you a report of what sports he is most likely to succeed. All this for $149, but is it worth it? The gene in question is ACTN3, a muscle-specific protein called alpha-actinin-3. There are variants of this gene that appear to be associated with optimal performance for different types of sports. As they state on their web site: " Simply put, this gene determines three types of athletes." They provide no data to support their claims. They test for the variant R577X and interpret the results as reported on their web site: http://www.atlasgene.com/

"Studies have shown that athletes having the variant in both copies of the ACTN3 gene may have a natural predisposition for endurance, such as distance running, distance swimming and cross-country skiing.

Athletes having the variant in one copy of their ACTN3 gene may be equally suited for sports requiring both endurance and sprint / power characteristics such as basketball, tennis, volleyball and cycling.

Athletes that do not carry this variant in either copy of the ACTN3 gene may have a natural predisposition for speed / power sports such as football, weight lifting and sprint events"

A good article on the subject was NYTimes published November 29, 2008. As they report, nearly 25% of elite endurance atheletes had 2 copies of this allele, only slightly higher than for the control group which was 18%.

Would you have made different decisions in your life if given this information as a child? Would you have your own child tested. I think I'll save my money and spend it on registration for AYSO soccer, Little league baseball, a decent bike, good shoes etc. He'll find out what he likes and what he's good at.

Is the Era of Personal Genomics Over?

An article reported in the New York Times this month highlighted concerns of geneticists and physicians over the use of personal genomics as a method for predicting diseases. Many companies have sprung up, such as 23andMe ($1000 a test), that use genome wide association studies (those which compare the genomes of patients and healthy people to look for certain alleles that occur in higher frequencies in people who have the disease than in healthy populations) to "assess" a person's risk for a particular disease. The companies take a DNA sample sent to them by the customer and sequence particular loci to look for allele variants that have been shown to occur in a higher frequency in people with the disease than in healthy individuals. Recently there has been outstanding criticism over the value of these association studies in predicting diseases. It seems that they reveal little about the genetic link to most diseases relative to the multimillion dollars they cost to produce. Do geneticists continue on this path of looking for common alleles found in the diseased population (by common, this usually means 4% of those who have the disease have this allele, versus 2% of healthy individuals have the allele, thus the person is theoretically twice as likely to contract the disease) or do they take a new direction and start sequencing the entire genomes of individual patients. The problem lies in that the diseases being looked at such as cancer, diabetes, heart disease are not the result of one or a few allele variants with pleitropic effects, which is the case for most rare genetic diseases suc as cystic fibrosis. Our assumption in genome wide association studies is that since these diseases are common in the population, we expected to find common genetic variations that cause these diseases in diseased populations but are absent in healthy populations. In taking this approach so far, we have found a few variants that are associated with some common diseases but they only a moderate disease risk at most has been shown. Some scientists argue that the confounding factors are large numbers of rare varients that will be undetected by performing genome wide association studies (a contradiction to those who believe that the common variants will identify the biological pathways through which a disease emerges, leading to possible drug targets). The possibility that hundreds of rare varients interacting to create a disease such as cancer makes a drug targeting a specific biological pathway seem daunting, if not impossible. Genome wide association studies will fail to find the rare variants with small effects and our resources should be put towards decoding full genomes of select patients. Others argue that genome wide association studies are useful tools in predicting risk for certain diseases, especially if one only considers diseases in which one's genes predict a 3 fold or greater risk for the disease than normal. Some scientists maintain that the underlying factor for risk is not rare allele variants, but unexpected biological mechanisms. It is unlikely that the era of personal genomics using genome wide association studies is over, however, sequencing entire genomes to discover rare variants is a worthy use of our time and resources.

Genetic art

Remember the fly where the eyeless gene is expressed inappropriately in the legs? An eye formed on each leg! Many gene names in Drosophila are named based on their mutant phenotype. That is a loss of function mutation in the gene eyeless produces a fly with no eyes. The eyeless gene is thus required for eye development. Question: Do the eyes on the fly "see"? Maybe yes. That is, there is an eye there with photoreceptors yet they are not wired to the brain of the fly so the fly is not aware of what the eyes see. What if a human implanted a hearing (artificial) ear under the skin of his arm equipped with a microphone to send sound signals to a computer? This is what performance artist Stelios Arcadiou (aka Sterlarc) has done. He intends to tranform his body into a portal for the internet. While this is not strictly an example of "genetic art" there are other good attempts as reported this week in the Science Times section of the NY Times Tuesday April 14th. Stelarc's art is one of several wonders of Post-natural history. There is a goat that has been genetically altered to produce the silk of spiders that can be used for bullet-proof vests, a forest of poles that transmit signals of your presence to a culture of neurons at the Georgia Institute of Technology. Among other expamples of "genetic art" include the transgenic cat that glows green due to the expression of GFP protein. Is this science, art or the grotesque remenescent of the displays of human genetic maladies for the entertainment of others for centuries. Time will tell. Meanwhile, artists offer society a of a potential that we as geneticist are (or should be) aware.

Biological clocks for men

The equal distribution of chromosomes during oogenesis is particularly error-prone for women. During meiosis, the process by which gametes form, the chromosomes undergo two divisions that reduce the numbers of each chromosome from the diploid number (2) to the haploid number (1n) found in germ cells. Too many chromosomes in an egg leads to trisomy and too few leads to monosomy. When this segregation goes awry, nondisjunction of chromosomes can lead to eggs with either too many or too few chromosomes. When fertilized by sperm the resulting zygote the extra copy of the chromosome that had failed to properly disjoin plus the normal 2n number of the rest of the chromosomes to give (2n+1). Those with trisomy 21 will have Down syndrome. Trisomy 13 leads to Patau syndrome and chromosome 18 to Edwards syndrome. Mental retardation and other clinically notable features are characteristic of those with Down Syndrome. These individuals live to adulthood and, depending on the severity of the syndrome, can live semi-independently. Those born with trisomy 13 and 18 usually live only a few hours or days after birth. Because of the risk of having a child with a trisomy increases as a woman ages, she is acutely aware of her life's arc with respect to child bearing. This risk increases dramatically from age 35 and onward so that the incidence of trisomy is a very real concern. But what about men? A recent article in the Sunday magazine of the New York times (4/5/09) reports that children born to fathers older than 40 years old have an increased risk of conceiving children that are likely to score lower than normal on tests of concentration, memory, reasoning and reading skills, at least through age 7. In addition there is a nearly 9-fold chance of a child having symptoms that fall into the range of autism spectrum disorder in men who become fathers at age 50 compared to 15-29 year old fathers.

So, whats up with nondisjunction and does this relate to fathers? Nondisjunction in females may be due to the inability of homologous chromosomes (the chromosomes a woman inherited by her mother and father, respectively) to hold together for decades. This is because the first stages of female meiosis occur in the fetus. In the first meiotic division, homologous chromosomes pair up and segregate from one another. The problem is that these chromosomes must remained paired until the time of ovulation. So if a women chooses to have a child in her 40's, those chromosomes have persisted in the paired state for 4-decades! It is amazing to think those chromosomes held together for so long, all 46 of them. In fact, many don't. While the incidence of trisomy among live births increases with age, so does the incidence of nonviable trisomies. Up to 30% of conceptions are thought to have at least one trisomy (or monosomy) and these are typically aborted spontaneously even before a woman even knows she is pregnant. Miscarriage is also often due to aneupolidy (having the wrong number of chromosomes) as well.

Men on the other hand have a stem-cell population from which sperm are formed continuously after puberty. Since every sperm comes from a brand new meiosis, the incidence of trisomy is less common. In addition, male meiosis appears to be subject to more robust mechanisms of surveillance to detect errors in chromosome segregation and arrest sperm development. The stem-cell population is not immune to other types of genetic errors including mutations or changes in chromosome modification patterns that might arise in the cell divisions leading up to spermatogenesis. Do these mutations lead to the higher incidence of mental disorders? The evidence is correlative at best. But perhaps men will begin to view the biological clock through the same lens as women; a view that weighs heavily on a woman planning on both a family and a career involving many years of post-graduate education.