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A mathematician by training, I discovered genetics in 2006 and never turned back. This blog was born to share all the fascinating things I learn about genes and DNA through my current research on viral genetics and HIV.

EE Giorgi
188 posts

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  • December 1, 2011
  • 10:06 AM

Genetic epistasis

by EE Giorgi in CHIMERAS

A while ago, in a post titled the Missing Heritability, I discussed the fact that some risk alleles (gene copies that have been found to increase the risk for a certain disease) may turn out to be counter-effected by other genes and thus explain why some people with these alleles never develop the particular disease. At the time I did a quick search on PubMed but couldn't come up with anything in the literature. Well, I was missing the keyword: epistasis. The word comes from the Greek "epi", whi........ Read more »

Pezawas, L., Meyer-Lindenberg, A., Goldman, A., Verchinski, B., Chen, G., Kolachana, B., Egan, M., Mattay, V., Hariri, A., & Weinberger, D. (2008) Evidence of biologic epistasis between BDNF and SLC6A4 and implications for depression. Molecular Psychiatry, 13(7), 709-716. DOI: 10.1038/mp.2008.32  

  • November 29, 2011
  • 08:41 AM

Sample size, P-values, and publication bias: the positive aspects of negative thinking

by EE Giorgi in CHIMERAS

If you follow the science blogging community, you may have noticed a lot of talking about sample size in the past couple of weeks. So I did my share of mulling things over and this is what I came up with.1- The study in question had a small sample size but reported a significant p-value (<0.05). Such study is NOT underpowered. An underpowered study is a study that does not have a sufficiently large sample size to allow detection of a significant result. A significant result is by definition a........ Read more »

  • November 26, 2011
  • 09:50 AM

I know that face! Sort of...

by EE Giorgi in CHIMERAS

In graduate school I had a Chinese friend who one day asked me the name of the fellow student who'd just stopped by to borrow a book. I told her, she thanked me, and added, "It's so hard for me to remember faces. You guys look all alike to me."Now, you have to understand that I'm petite, brunette with dark eyes (very Italian), and the girl she'd just asked about was the typical Northern European type, tall, blond, and blue eyes. The concept was truly intriguing. I tend to mix up Eastern A........ Read more »

  • November 22, 2011
  • 08:18 AM

Don't forget the editor! Or: the fundamental role of RNA editing

by EE Giorgi in CHIMERAS

The genome is a plastic thing. Yes, you heard me right: the genome is plastic. No, it's not true that an individual's DNA doesn't change. It's not true that genes dictate what we are, and it's not true that DNA is just a set of instructions. And that we can "build" an organism by simply giving a string of As, Gs, Ts, and Cs.No.There's so much more to genomes than nucleotides and genes. If you've been following me from my very first post back in July, I hope the message has come through now. Epig........ Read more »

  • November 19, 2011
  • 09:30 AM

Of hierarchies, mice, and neurons

by EE Giorgi in CHIMERAS

It's shared across very different species, from ants and bees all the way up to chimpanzees and humans: social hierarchy dictates the structure of a group, and the ability to correctly recognize an individual's status, as well as their own, is crucial to successful interactions in the group.Interestingly, social cognition is distinct from social status recognition, as demonstrated by studies on humans with brain lesions [1]. Neuroimaging also revealed that social status recognition has it........ Read more »

  • November 17, 2011
  • 09:53 AM

The immortality paradox

by EE Giorgi in CHIMERAS

My friend Tim Bowen posed a really interesting question. Tim is a retired Los Angeles Police Officer, a writer, and a fantastic story teller. If you don't believe me, check out his book (Kindle edition available from Amazon), a collection of stories from when he was an LAPD street cop. A forewarning, though: don't read it in public places unless you don't mind people staring at you. Before you know it, you'll burst out laughing and everybody will be wondering what you've been adding to your brea........ Read more »

Jaskelioff, M., Muller, F., Paik, J., Thomas, E., Jiang, S., Adams, A., Sahin, E., Kost-Alimova, M., Protopopov, A., Cadiñanos, J.... (2010) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature, 469(7328), 102-106. DOI: 10.1038/nature09603  

  • November 15, 2011
  • 11:04 AM

The case of "junk DNA" and why it shouldn't be called junk: RNA.

by EE Giorgi in CHIMERAS

This is part 5 of 5 in a series dedicated to the concept of "junk DNA". Links to the previous parts: Part 1, Part 2 (redundancy), Part 3 (epigenetics), and Part 4 (topology).I recently discovered the work of John S. Mattick (who's written many beautiful reviews on RNA) and learned a new concept, which he discusses in [1]: while the number of protein-coding genes is relatively constant across complex species, non-coding DNA increases with developmental complexity.Isn't it intriguing? You see, whe........ Read more »

Mattick JS. (2011) The double life of RNA. Biochimie, 93(11). PMID: 21963144  

Dinger ME, Gascoigne DK, & Mattick JS. (2011) The evolution of RNAs with multiple functions. Biochimie, 93(11), 2013-8. PMID: 21802485  

  • November 12, 2011
  • 10:16 AM

An addendum on Haldane's dilemma and the use of mathematical models

by EE Giorgi in CHIMERAS

Last week, my post on Haldane's dilemma garnered many views. I'm glad people are reading it and I hope they find it useful in clarifying the great impact of Haldane's 1957 paper. For those of you interested in digging deeper into the topic, the Panda's Thumb discusses the matter in a 2007 post, and Gene Expression covers it here. I just have an additional note, which is a bit of a pet peeve of mine, but as I read about the reactions to Haldane's paper scattered all over the Internet, I realized........ Read more »

Haldane, J. (1957) The cost of natural selection. Journal of Genetics, 55(3), 511-524. DOI: 10.1007/BF02984069  

Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H.... (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America, 105(21), 7552-7. PMID: 18490657  

  • November 10, 2011
  • 08:53 AM

What shall we play today? How about a protein folding game?

by EE Giorgi in CHIMERAS

So, after hearing all the talking about it, I finally did it. I checked out Foldit, the online scientific discovery game. I'm sure you've all heard of it, and many of you may have even played with it -- if so, please share your experience in the comments because I'd love to hear about it! Developed by researchers at the University of Washington, the beta version of Foldit was released in 2008. Players compete to solve protein structures that would otherwise require an enormous amount of computin........ Read more »

Khatib, F., Cooper, S., Tyka, M., Xu, K., Makedon, I., Popovic, Z., Baker, D., & Players, F. (2011) Algorithm discovery by protein folding game players. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1115898108  

  • November 8, 2011
  • 08:06 AM

Gene inactivation and the female immune system

by EE Giorgi in CHIMERAS

Genes don't usually disappear from a genome. However, a mutation that affects the transcription of the gene can induce its loss of function. For example, a mutation could introduce an early stop codon -- a bit of DNA that interrupts transcription. The result is a truncated RNA that can't make a functional protein. Such a mutation inactivates the gene because it can no longer produce the protein it was coding. Gene inactivation is a mechanism that has shaped evolution by allowing new genes to rep........ Read more »

Ghaderi, D., Springer, S., Ma, F., Cohen, M., Secrest, P., Taylor, R., Varki, A., & Gagneux, P. (2011) Sexual selection by female immunity against paternal antigens can fix loss of function alleles. Proceedings of the National Academy of Sciences, 108(43), 17743-17748. DOI: 10.1073/pnas.1102302108  

  • November 5, 2011
  • 08:58 AM

Haldane's dilemma

by EE Giorgi in CHIMERAS

  Today is JBS Haldane's 119th birthday. Together with Fisher and Wright, Haldane is considered the founder of the mathematical theory of population genetics. Population genetics studies how allele frequencies (the prevalence of different copies of genes) change in populations due to processes like natural selection and genetic drift. In other words, how mutations arise and how they undergo a turnover in the population. To celebrate Haldane's birthday, I thought I'd discuss his 1957 paper, ........ Read more »

Haldane, J. (1957) The cost of natural selection. Journal of Genetics, 55(3), 511-524. DOI: 10.1007/BF02984069  

  • November 2, 2011
  • 09:22 AM

A battle for transcription regulates bacterial conjugation

by EE Giorgi in CHIMERAS

Genetic information is transmitted in two modes: when we talk about the slow accumulation of mutations across generations, we are talking about vertical gene transfer, in other words, the transmission of genetic alleles from the parents to the offsprings. Genetic material can also be transferred "horizontally" when an organism incorporates another individual's genetic material without being the individual's offspring. A genetic chimera is an example of a horizontal gene transfer. You can pictur........ Read more »

Chatterjee A, Johnson CM, Shu CC, Kaznessis YN, Ramkrishna D, Dunny GM, & Hu WS. (2011) Convergent transcription confers a bistable switch in Enterococcus faecalis conjugation. Proceedings of the National Academy of Sciences of the United States of America, 108(23), 9721-6. PMID: 21606359  

  • October 31, 2011
  • 11:50 AM

The "jumping genes" of the brain

by EE Giorgi in CHIMERAS

Have you ever wondered how a single cob of Indian corn can display so many beautiful colors? The answer came in 1948 thanks to scientist Barbara McClintock: she discovered that 50% of the maize genome is made of transposons, DNA sequences that can "jump" around in the DNA of a single cell. As they move around, these "jumping genes" can "stretch" the DNA by adding repeated copies, but they can also cause new mutations to appear. In the case of corn, the new mutations are responsible for the diffe........ Read more »

Cordaux R, & Batzer MA. (2009) The impact of retrotransposons on human genome evolution. Nature reviews. Genetics, 10(10), 691-703. PMID: 19763152  

Baillie, J., Barnett, M., Upton, K., Gerhardt, D., Richmond, T., De Sapio, F., Brennan, P., Rizzu, P., Smith, S., Fell, M.... (2011) Somatic retrotransposition alters the genetic landscape of the human brain. Nature. DOI: 10.1038/nature10531  

  • October 27, 2011
  • 08:41 AM

P53, the anti-cancer sentinel

by EE Giorgi in CHIMERAS

  In my post The Missing Heritability, I hinted at what I called "protective mutations." We know that people with "risk alleles" have a higher probability of developing certain cancers, but what about people who do have those alleles and never end up developing the cancer? Do they carry "protective alleles" that counter-effect the negative risk carried by the deleterious alleles?An astute reader (thanks!) pointed me to the tumor-suppressant protein p53. I dug up the literature on this, and ........ Read more »

Hu R, Peng G, Dai H, Breuer EK, Stemke-Hale K, Li K, Gonzalez-Angulo AM, Mills GB, & Lin SY. (2011) ZNF668 Functions as a Tumor Suppressor by Regulating p53 Stability and Function in Breast Cancer. Cancer research, 71(20), 6524-34. PMID: 21852383  

Neilsen PM, Cheney KM, Li CW, Chen JD, Cawrse JE, Schulz RB, Powell JA, Kumar R, & Callen DF. (2008) Identification of ANKRD11 as a p53 coactivator. Journal of cell science, 121(Pt 21), 3541-52. PMID: 18840648  

  • October 24, 2011
  • 08:48 AM

The missing heritability

by EE Giorgi in CHIMERAS

It's been dubbed the "dark matter of the genome" because… we know it's there and yet we can't find it. Ever since the completion of the Human Genome Project, the hunt to disease variants has taken up much, if not most, of genetic research. The idea is simple: we take a sample of healthy people (the controls), a matched sample of diseased people (the cases), we type their DNA, stratify by other possible factors (this one depends on the study, but think of things like smoking, age, family histor........ Read more »

  • October 19, 2011
  • 09:11 AM

MHC molecules, mating, sniffing, and birthcontrol: believe me, there's a link!

by EE Giorgi in CHIMERAS

Today we talk about… mating! Whoa -- did you just see that spike in the stats page? Haha, okay, but first you have to sit through the usual genetic lesson. Here it goes: we start talking about the major histocompatibility complex, or MHC.I've mentioned many times in my previous posts that in order to trigger an immune response you have to make sure that the immune system recognizes the antigen, or "foreign" object. Antigens are made of proteins that, once inside the cell, are chopped into bits........ Read more »

Wedekind C, Seebeck T, Bettens F, & Paepke AJ. (1995) MHC-dependent mate preferences in humans. Proceedings. Biological sciences / The Royal Society, 260(1359), 245-9. PMID: 7630893  

Roberts SC, Gosling LM, Carter V, & Petrie M. (2008) MHC-correlated odour preferences in humans and the use of oral contraceptives. Proceedings. Biological sciences / The Royal Society, 275(1652), 2715-22. PMID: 18700206  

  • October 16, 2011
  • 09:12 AM

A chimeric virus to cure leukemia? Yes, we can!

by EE Giorgi in CHIMERAS

Last week I talked about gene therapy and vaccines targeting tumor cells. Following those posts, a friend of mine (thanks, Alex!) pointed me to a recent case report published in the New England Journal of Medicine, which successfully used gene therapy to treat leukemia [1]. Since you know I like to talk about chimeric viruses and all the wonderful things you can do with them, I was instantly drawn to the paper. Leukemia is a type of cancer that causes an abnormal increase in white blood cells......... Read more »

Porter, D., Levine, B., Kalos, M., Bagg, A., & June, C. (2011) Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia. New England Journal of Medicine, 365(8), 725-733. DOI: 10.1056/NEJMoa1103849  

  • October 12, 2011
  • 10:51 PM

Are vaccines the future of cancer treatment?

by EE Giorgi in CHIMERAS

The September issue of the Cancer Journal is dedicated to cancer vaccines and how they may hold the key for cancer treatment and prevention. This is not to be confused with vaccines against cancer-causing viruses, like HPV. In that case the vaccine elicits antibody responses against the virus. In the context of cancer, though, a vaccine would use the immune system's own weapons in order to destroy tumor cells. An example is the vaccine to treat advanced prostate cancer that was approved by the F........ Read more »

Dhodapkar MV, & Dhodapkar KM. (2011) Vaccines targeting cancer stem cells: are they within reach?. Cancer journal (Sudbury, Mass.), 17(5), 397-402. PMID: 21952290  

Perez SA, von Hofe E, Kallinteris NL, Gritzapis AD, Peoples GE, Papamichail M, & Baxevanis CN. (2010) A new era in anticancer peptide vaccines. Cancer, 116(9), 2071-80. PMID: 20187092  

  • October 11, 2011
  • 06:17 AM

Facebook and the unselfish gene

by EE Giorgi in CHIMERAS

So I finally did it. As some of you regulars may have noticed, I put the blog on Facebook. And then I instantly became needy and sent out a bulk of emails begging people to like me. I sent out five and since they're very nice friends of mine, they all liked me. And then I thought, "Well, now, my friends' friends' will like me, and then my friends' friends' friends', and then..."Hmm. That got me thinking. Does it work like with viruses? No, seriously, do "likes" spread like a viral infection in t........ Read more »

Benkler Y. (2011) The unselfish gene. Harvard business review, 89(7-8), 76. PMID: 21800472  

  • October 6, 2011
  • 08:41 AM

How a virus can teach us neuroscience

by EE Giorgi in CHIMERAS

Back in college, the shortest theorem proof I sat through in class (I was a math major) was the following: "Suppose the topological manifold is a chunk of cheese. Put a mouse on one of the cells and wait until the mouse has eaten all of the cheese." The cells, in that context, weren't biological cells, but rather topological ones. Believe me, it was a real proof and, once you worked out the details, it held.So now suppose that instead of cheese you have a brain, and instead of topological cells ........ Read more »

Beier, K., Saunders, A., Oldenburg, I., Miyamichi, K., Akhtar, N., Luo, L., Whelan, S., Sabatini, B., & Cepko, C. (2011) From the Cover: Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors. Proceedings of the National Academy of Sciences, 108(37), 15414-15419. DOI: 10.1073/pnas.1110854108  

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