It's One of A Kind

After learning about the genome study in Berkeley it sparked my interest and led me to this article. The article “ From Californian’s DNA project, a Giant Genome Project” from the New York Times boasts that it is the largest human genome study of its kind. The purpose of the genome study is to find out the underlying genes related to chronic diseases and to discover ways that people can live longer. What makes this study is different from other genome wide studies are not only because of its large sample size, but also that each individual genome will be analyzed and paired with its medical history.

Kaiser Permanente and the University of California, San Francisco is jointly conducting the genome-wide association study. Cells for analysis are extracted from the spit of 10,000 volunteer members of Kaiser Permanente. As a Kaiser member myself, I did not know about this project. However, if I were asked to volunteer I would have gladly taken the offer. This genome wide study is used to compare genes with people of who have been diagnosed with chronic diseases such as multiple sclerosis and cancer with those of people who are currently healthy. The team from UCSF led by Elizabeth Blackburn, will analyze the samples and measure the length of the telomeres. In turn, they hope to find a correlation between telomere length and one’s medical history. The study is to be finished in less than 18 months. The technology is now advancing so quickly that it is progressing from the lab to the home. However, unlike the Berkeley study these samples do not give volunteers the option to review their results. The names of the volunteers are quickly erased and replaced with codes, therefore only the researchers can link their genomes to their respective medical histories. Kaiser will keep continue the project for the next few years spending about 9 million dollars to retain the samples.

Similar to the Berkeley study, it is unsure if the information gained in the study outweighs the disadvantages or consequences that may occur. Are we going to learn anything new from the results? In addition, is the information gained from the project worth the millions of dollars it is going to cost? I guess we will have to wait and see if the genome study is worth the effort and money it needs

Link to Citation: http://www.nytimes.com/2010/05/30/science/30sfgenome.html?fta=y

X-rays can cause reverse mutation in D. melanogaster

Dr. Mel Green is a professor Emeritus of Molecular and Cellular Biology here at UCDavis. He was garnered many prestigious findings throughout his long career in genetics and has worked at many top universities and worked with many others who have been integral in discovering more about genetics. Dr. Green came to our MCB 164 class and gave a spectacular guest lecture, the best part of which was when he told us to put down our pencils. He described to us how he came to work with Drosophila and how he discovered many of the things he did including the discovery of mobile DNA elements. I was curious to see how exactly Dr. Green was involved in finding out that x-ray's could produce reverse mutations and i found this article where he and a colleague here at Davis figured it out using the vinegar flies.


In this experiment, Green was discussing how different experimenters found contradicting evidence that this could be done. He questioned the current techniques many people were using for reverting mutations and his main goal was to definitively prove that x-ray's can in fact induce reverse mutations. Some also found that the rate of reverse mutation was lower than that of direct mutation. Based on the other experiments Green could also see that different alleles and species had different rates of reverse mutation. He postulated that the differing results stemmed from the theory that perhaps some forks were irreversible while others were, which gave rise to opposing papers. Specifically, he wanted to test in this experiment whether or not out of the 4 variable forked alleles, whether or not each allele would allow a reverse mutation or not.
He exposed the males and females to 5000 rads and 4000 rads, respectively. He then mated each sex to an opposite sex that has not been irradiated. he screen for various phenotypes including bristle type, eye color, and body color to see if revertants were produced.
His experiments yielded surprising results, he found that none of the male sperm alleles gave rise to reverse mutations, but one specific allele (f3n) for homozygous females clearly showed a high frequency of reverse mutations.

In his discussion he acknowledges that male sperm are haploid and the female flies were diploid which may have something to do with the results, but he also noted that during spermatogenesis there is NO crossing over while in oogenesis there is. Which led to another question: Does reversibility of mutations have to do with crossing over ability?I just found it quite interesting that x-rays can return a mutant allele to completely wild-type, leading to a production of completely normal looking female flies.


Lefevre, G, Jr., Green, M. M., 1958, Reverse mutation studies on the forked locus in Drosophila Melanogaster, Genetics, v. 44, p. 769.

Genetic Switch - The Key to Conquering Memory Loss?

Along with eyesight, hearing, and other abilities we take for granted during our youth, our sense of memory also (generally) decreases with age. Recent research has found a relationship between the amount of DNA acetylation in brain cells and the effects it has on forming memory in mice. This discovery has the potential to decipher the memory-making process in humans and perhaps lead to a drug concoction that will solve the “issue” of forgetfulness.

To study the correlation between age and memory, initial research compared the memory capacity of young mice versus older mice. These mice were placed in boxes with various sensory cues that they should be able to remember; these mice were then given a foot shock in this box. 24 hours later, young mice “froze in fear” when they were placed in the same box. Older mice (middle-aged 16-month old) acted as they normally would because they could not recall the foot shock they received in that box just 24 hours ago.

Andre Fischer's team of the European Neuroscience Institute in Gottingen, Germany delved further into this evidence by trying to figure out what specifically was causing this decline in memory with age by looking at tiny chemical changes that may affect how memory genes are switched on and off. Information from previous studies have shown that over 1,000 genes are involved in the memory-making process. To activate these “helper genes”, tightly wrapped DNA has to be loosened by acetyl groups to signal that these helper genes are ready to start the process of storing memory.

Fischer's team found that older mice have fewer acetyl groups present compared to younger mice when the memory of pain and danger of the box and foot shock were supposed to start processing and storing in the brain. When researchers injected a drug that helps increase histone acetylation in older mice, these mice reacted and stored the memory of the shock just as well as the younger mice. If humans form memories like mice, increasing acetylation may help older people combat memory loss.

While these findings are exciting, it is obvious that much more research needs to be done before applying any sort of memory-boosting drug or treatment to humans. One problem is that acetylation occurs in various body processes, so this memory drug would have to specifically target brain cells. We also have to debate the question of whether it is beneficial to add another drug to the collection of other drugs people are now taking in the quest for immortality. Another question we can also ask is whether the ability to forget is actually underappreciated. While college life might be deemed as the “best years of your life” and while it would be great to remember all those facts for the final exam, it is possibly a blessing that some of these college day shenanigans are forgotten as we grow older.

Sanders, Laura. “Genetic Switch Makes Old Mice Forgetful.” ScienceNews. May 2010. Web. 28 May 2010. <http://www.sciencenews.org/view/generic/id/58940/title/Genetic_switch_makes_old_mice_forgetful>.

Agis-Balboa, R.C., Bahari-Javan, S., Burkhardt, S., Chen, W., Cota, P., Dettenhofer, M., Farinelli, L, Fischer, A., Gogol-Doering, A., Kang, H., Opitz, L., Peleg, S., Salinas-Riester, G., Sananbenesi, F., Wittnam, J.L., Zovoilis, A., (2010). Altered Histone Acetylation Is Associated with Age- Dependent Memory Impairment in Mice. Science, 328, 753-756.

Sex Determination in Drosphilia Melanogaster

The species Drosphilia melanogaster has been critical to the development of genetics for generations. Their simple life cycle and easily identifiable characteristics have made the species one of the most essential model organisms in the field. One of the species defining traits includes the ability with which one can easily identify the sex of these flies by simple physical features. This has allowed them to be important to the study of dosage compensation and sex determination. However, a study conducted at the Janelia Farm Research Campus of the Howard Hughes Medical Institute may forever change the views of sex determination in the cells in Drosphilia.

Until recently, it was believed that all of the cells in the fruit fly express the genes that determine maleness or femaleness but that only some regions of the body exhibit external characteristics while other regions seem physically identical regardless of sex. This study suggests that not all the cells in a fruit fly's body are the same but are mosaic, with different cells expressing the doublesex gene in different patterns while other cells not expressing it at all. Doublesex (dsx) is a critical gene for sex determination along with other genes such as fru. By using molecular biology, the scientists observed dsx expression in both larval and adult flies in order to study the location and conditions required for gene activation. The researchers began by inserting a GAL4 gene into a dsx locus through homologous recombination. They then partnered this sequence with a reporter gene, allowing them to track the cells expressing dsx. Their findings were quite significant.

Overall, this study resulted in several important findings. In addition to shedding light on how dsx regulates sexual development by controlling transcription factors and cell-cell signaling molecules in specific cells and tissues, the study illustrated that dsx acts on different aspects of sex at different times, even within one cell lineage. Also, up to this point, sex differentiation was considered to be an adult characteristic in flies but the results demonstrate that dsx is even expressed in the late third instar larval fat bodies. However the most significant finding was that dsx was not expressed in all cells. Looking at the evolutionary level, the results suggest that dsx and fru arose through modifications of the genes’ cis-regulatory regions. This implies that the pattern of sex determination present in current Drosphilia resulted from evolutionary selection for individuals who did not express sex determining genes throughout the body. Such expression of dsx may perhaps even hinder an individual’s overall fitness.

As the article in the Science Daily explains, the consequences of this find are huge on both a molecular and evolutionary level. If the cells in Drosphilia are mosaic and do not all undergo sex determination, then some of the XX and XY cells in one sense are not sex specific. What does this mean for other species? Many other species control sex determination through genes analogous to doublesex. How would such findings in C.elegans, zebafish or mice affect our understanding of sex differences? To then apply such considerations to higher species such as humans or other larger mammals may entirely change the way we consider sex differences. Only time and further research will determine what the implications of this finding will mean for our understanding of sex differences.

Link to article: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000365

Citations:

Public Library of Science. "Male or Female? In Flies, Some Cells Can't Tell." ScienceDaily 5 May 2010. 30 May 2010 .

Robinett CC, Vaughan AG, Knapp J-M, Baker BS. Sex and the Single Cell. II. There Is a Time and Place for Sex. PLoS Biology, 2010; 8 (5): e1000365 DOI: 10.1371/journal.pbio.1000365

Dirty Fingertips May Leave Forensic Clue

As we all know, bacteria are found practically anywhere including our hands and the things that we touch. A study published in March 2010 by Noah Fierer and his team suggests that bacteria from a person’s hands could one day be used to accurately identify that individual. If this is true, we will be able to track down criminals who remove their fingerprints and/or leave no DNA evidences (such as saliva, tissue, blood, or semen) from the bacteria trail they leave on the objects they touch. Fierer says that a human hand can contain up to 100 different species of bacteria and only ~13% of the same makeup is shared between any two individuals.

Fierer and colleagues did a test to see whether bacteria on an object are more similar to the bacteria found on the owner’s skin than to bacteria on the general population. They compared bacteria sequences found on 9 computer mice to bacteria collected from the hands of 270 individuals. The results suggest that bacteria from each mouse closely matched those from the owner’s hands. Fierer says that this technique was 70% - 90% accurate overall but the percentage could increase as the technology becomes more sophisticated.

Although this intervention attracts many interests, there are limitations of this technology. For example, a professor from Stanford University, David A. Relman, says that it isn’t possible yet to separate mixed-up bacterial trails when more than one person touches the same object. Also, there could be changes to the distribution of bacteria once they left the human hand, thus making it harder to link the microbes to a person.

Personally, I think DNA evidences are more reliable than this technique especially since we already have a large database which we can use to crosscheck the DNA we find on a crime scene. The bacterial trails technique, in the other hand, requires us to have a sample from the suspect whom may not be identified yet.




Fierer, N., Lauber, C. L., Zhou, N., McDonald, D., Costello, E. K., & Knight, R. (2010). Forensic identification using skin bacterial communities. PNAS , 6477-6481.
Khan, A. (2010, March 16). Bacterial trail may be next forensic clue. Retrieved May 26, 2010, from LA Times: http://www.latimes.com/news/science/la-sci-bacteria16-2010mar16,0,5990278.story

Horizontal Gene Transfer in Higher Eukaroyotes

A Role for Host–parasite Interactions in the Horizontal Transfer of Transposons Across Phyla

http://www.nature.com/nature/journal/v464/n7293/abs/nature08939.html

Horizontal gene transfer is a process that geneticists have mostly studied in bacteria, and is offered as a possible explanation to how bacteria are able to quickly become antibiotic resistant. But only recently has this same process been documented in higher organisms, thanks to the work Gilbert et al. The findings in this article pose an interesting question: do higher organisms transfer genes to other species more often than originally thought?

Simply put, this article argues that there is a type of parasitic blood-sucking bug that feasts on tetrapods in many different phylas, and is causing horizontal gene transfer (HGT). Although we haven’t gone over this extensively in class, many of us have heard about HGT in other classes we have taken. In HGT, an organism incorporates genetic material to another organism without being the offspring or a mate of that organism. This phenomenon is noted mostly in unicellular organisms, and so I found it really interesting that this bug could inflict HGT on animals of higher complexity.

The authors of the article uses a few different phylogenies to show how the animals affected by the mites are not closely related and are from different regions of the world, and therefore should not have too much similar DNA. To give an idea, some of the animals included are opossums, squirrel monkeys, frogs, lizards, and chickens. Then, from these dispersed animals, the researchers sequenced genomes and found a portion of genes shared amongst all of the animals and the mites. They therefore concluded that this is proof of HGT within these phyla. HGT mechanisms are still not clearly understood, and so how genes are transferred is not specifically talked about in this paper. Because of this and the fact that there may be other factors causing similar sequences (such as unknown distant relatives), I’m not really sure if I believe this paper or not. It seems too far-fetched that the authors randomly chose species and they all had the sequences in common with the mite. I feel like there is a lot missing from the article, and I would like to see data on animals that are more closely related to all of the species. I feel like I need proof that related species to the ones in the study who are not parasitized by the bug do not also have the same sequence. If I saw this data, I might be more inclined to believe that HGT can be caused by a parasitic bug across many multicellular phyla. All in all, this article leaves me wanting more information on just how common HGT is in higher organisms and it will surely be interesting to learn.

Clement Gilbert1*, Sarah Schaack1*, John K. Pace II1, Paul J. Brindley2 & Cedric Feschotte1

“A role for host–parasite interactions in the horizontal transfer of transposons across phyla”

Nature Vol 464 April 2010 (p 1347-1352)

Forensic Analysis of DNA

An article in the May edition of Scientific America, entitled Portrait in DNA, discusses the possibility of using DNA to create police style sketches of criminals. This seems to be possible considering scientists recently published a sketch (pictured above) of a 4000 year old ancient Greenlander drawn solely from his DNA remains. All the DNA used came from a small clump of hairs that had been preserved in the permafrost! The scientists first determined that the man was of North Asian decent based on a pattern of DNA variations most commonly found in Siberian populations. They then interpreted single nucleotide polymorphisms (SNPs) in four genes linked to brown eye color in modern Asians. They also found SNPs associated with shovel-shaped front teeth, dry ear wax, and dark skin. They also found variations typical in populations that have adapted to cold indicating that the man had ample body fat. Using this type of analysis of criminal DNA would greatly help investigators find the criminals, especially when there are no witnesses to give a description to an artist. Scientists at George Washington are in the process of developing forensic kits that would determine the subjects eye and hair color, sex and ancestry. However age is difficult to determine because although scientists could took at telomeres, the chromosomal ends that shrink with time, there are many health and environmental factors that influence shrinkage.
The ancient Greenlander was also identified as having a high risk for hypertension and diabetes. Some scientists worry about the ethics behind announcing such discoveries about a criminal to the world, for example the fact that the criminal has a high likelihood of being obese, a smoker, an alcoholic or depressed. Clearly medical privacy is an issue here but if this technology could help us find killers, isn't it worth it? I do hope that a forensic kit as mentioned would only be released and used once it was completely reliable. Unreliable information about physical appearance of the a criminal would only hinder the investigators job.
Tiffany Flossman