Good morning all, We've talked about genes, and modifications of gene structure (gene editing) or use (gene expression) a number of times this term, and I am sure that you understand both the power and peril that these methods embody. Editing DNA is, at its most basic level, very profound: it really is the 'stuff' that defines us. In the science news this week comes a recent report, that at first glance, seems unimportant: scientists have performed gene editing, and made an albino lizard. But, this simple summary doesn't quite capture the importance of this work. For most of its history, molecular biology (and its recent growth into genomics) have focused upon a few model organisms, chosen for their practicality of study. These have included bacteria, yeast, roundworms, fruit flies, zebrafish, and mice, to name a few. Much has been learned from these models, and most of what we know about molecular biology and genetics comes from work on them. But, their use excludes several prominent groups of organisms, including birds and reptiles. That may be coming to an end. One research group recently employed a modern gene-editing technique (CRISPR) to modify gene expression in Anolis lizard eggs to produce albino offspring. This, in and of itself, is not necessarily an earth-shattering result. What is new is the fact these researchers were able to use CRISPR on a new family of vertebrates, suggesting that it really is going to be a general and powerful technique. Even more importantly, however, these researchers were able to edit the genome of immature eggs, which means that the effects they caused were then propagated throughout the entire organism that resulted from those eggs. Remember when we talked about gene therapy, and introducing new genes into specific tissues (only)? Here now is a more powerful technique: performing targeted gene editing on the whole-organism genome. http://www.sciencemag.org/news/2019/04/game-changing-gene-edit-turned-anole-lizard-albino Stay tuned: this gene (and now genome) editing ride is going to be a wild one for a few years, until our understanding of it, our ethical evaluations, and our regulations mature. Have a great weekend - Dr. Nealen
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Good morning all, In our last two lectures of this third unit of the course, we are considering renal function and the often overlooked role of the kidneys in our health and well-being. During lecture on Thursday, I mentioned several facts related to kidney disease and failure that some recent science news can inform. We discussed conditions such as diabetes and hypertension that can induce kidney damage and failure, and the third items on that list was genetic bases for kidney ailments. One of the reasons that we did not elaborate on the topic is that the specific genetic causes of kidney disease (like that of so many other of our diseases) is very nebulous - there are many genes involved, often with very weak effects, and their interactions with each other and with environmental influences are poorly understood. In these situations, patients often recognize that they are part of a family history of disease (suggesting its genetic basis), but typically the genes involved are not identified, or their function is not characterized. Recently, several research teams have made progress on this issue. Using exome sequencing (a DNA sequencing method that focuses only upon the protein-coding regions of our DNA), researchers recently have described with greater detail the number of different genes involved in a small sample of patients with chronic kidney disease. They identify over 60 different genes, some with identified roles as membrane transporters or regulators of gene expression. Most of these were associated with a tiny number of disease cases. http://stm.sciencemag.org/content/11/474/eaaw0532 As is often the case, studies like this are useful if only because they reveal how much we have yet to learn, and offer a potential method forward. It's a very long (and expensive) pathway from gene identification, to functional investigation, to testing of therapeutics, to useful treatments, and most avenues of exploration do not yield breakthroughs. But, we now know more than we did, and there is great interest in finding ways to abate kidney disease. There are still a great number of people awaiting kidney transplants, and many die while they wait. Inequities of access to donated organs may be part of the problem. Perhaps we should pay people for organ donation - or would that be more problematic than useful? https://www.washingtonpost.com/opinions/the-us-organ-transplant-system-is-broken-but-the-latest-fix-will-make-it-worse/2019/04/02/41ef2b1c-555b-11e9-8ef3-fbd41a2ce4d5_story.html https://www.washingtonpost.com/opinions/what-if-we-paid-people-to-donate-their-kidneys-to-strangers/2019/01/08/6f397a0c-1391-11e9-b6ad-9cfd62dbb0a8_story.html Have a great weekend - Dr. Nealen Good morning everyone, In our lab this term, we have talked numerous times about the 'central dogma of information flow', the idea that information encoded in DNA is used during the process of transcription to make RNA, which itself is used during translation to make protein. This concept is part of the 'one gene, one protein' idea, that each gene encodes information to make a single type of protein. During our discussions, we've also used estimates of the number of genes that we possess (perhaps 25,000), and our most recent lab included discussion of how effective any single one of them may be in influencing phenotype. Most individual genes are likely to have little or no obvious effects on phenotype, while some 'master regulator' genes, or other single genes that are responsible for the production of a key molecule in a cell, may exert more-pronounced effects. In the news this week comes description of one such gene (gene FAAH, so called), which had been identified previously but whose function was unknown. It is now known that it is a crucial player in mammalian pain perception, for a woman has been described who has led a 'pain-free' life, and who has a genetic mutation in this one gene. Interestingly, this mutation also influences mood - she is described as never feeling anxiety as well. https://www.livescience.com/65100-woman-cant-feel-pain.html While pain is unpleasant, do not wish for none of it, for it is a useful 'warning system' that alerts us to tissue damage. There have been others described who 'feel no pain', and their existence is pretty awful, for they experience injury after injury (many of them self-inflicted). Much of their story was described in a superb documentary from a few years ago, entitled A Life Without Pain - if you are interested in the topic, it is very worthwhile. The subject in this most recent report is mostly, but not entirely pain-free, so her life is mostly normal. But, her case illustrates well the potential power of individual genes. They need not always be 'master regulators' to have individually-profound effects. Sometimes, being just a single link in an important chain is crucial. Have a great weekend - Dr. Nealen Good morning, As we conclude our regeneration experiment this week, a new study comes along that suggests that part of the regeneration process is regulated by 'master genes', a concept that we explored earlier during our discussion of 'snake genes and human spines'. While our recent evaluation of regeneration focused upon stem cells, remember that it is the genes that these cells express that ultimately determines their cellular fate. This new study suggests that one particular gene EGR ("early growth response") is necessary for regeneration to occur. This new study showed that EGR activation is necessary for regeneration in the marine three-banded panther worm (very similar to the planaria we used in our lab). While much remains to investigate regarding EGR and its function, the authors do note that humans also possess this same gene, and that it is known to be activated by injury. So, these studies performed in tiny flatworms are very relevant to us. And, once again, the topics we explore in lab remain at the forefront of genetic science. Very cool, I think! https://www.nytimes.com/2019/03/20/science/worm-regeneration.html Have a great weekend - Dr. Nealen Good morning all, I'm sure that you have heard recent news about gene editing that was performed on two human embryos by a Chinese scientist, in an attempt to introduce resistance to HIV infection. His efforts only came to light after the children were born, and have been roundly criticized as 'crossing the bridge too soon' - there seems to have been little or no oversight of his work, and most geneticists agree that it is too early for us to consider human genome editing, before we better understand the risks, and the opportunities, it poses. But, calls for a moratorium on this type of work are not universal - some believe that the time is now to proceed, and that the potential risks of waiting are greater than the potential for doing harm. Others say that this is simply scientific progress - messy, risky, but in the end, advancing our knowledge and capabilities. That this debate is prominent in the science literature is a sign that this is truly the cutting-edge of research and its application. I'm sure that we haven't heard the last on this issue, and I also am sure that in your lifetimes there will be increasing opportunity to perform exactly this kind of genome editing. Think about children you might have in the future - would you edit their genomes to improve their health? Or to make them smarter? Or kinder? What if you could only choose one of these characteristics? What if improving one caused reductions in another? There is still much to learn, and much to discuss... https://www.sciencemag.org/news/2019/03/new-call-ban-gene-edited-babies-divides-biologists?utm_campaign=news_weekly_2019-03-15&et_rid=17390186&et_cid=2717665 Hope that you all have had a great Break, and are ready for the second half of our semester! I have been taking care of our planaria, and they are almost ready for your evaluation. Travel safely back to campus - see you on Wednesday. Dr. Nealen Good morning everyone, As I scan the science news each day, I often read articles that are interesting, and potentially useful. Less frequently do I encounter news reports that make me say 'wow!". Here is a link to a news report about a recent study that did, for it potentially changes something that has been fixed for perhaps a billion years. You've heard much about DNA in your lecture and our lab, and you know the basics of its structure: two twisted strands of a sugar-phosphate backbone, with paired nucleotides along their length. You also know that the nucleotides in use are four only (A, C, G, and T) and that they pair in only two possibilities (A-T, C-G). Recently, scientists have created synthetic DNA molecules that have not four, but eight different nucleotides (by adding synthetic nucleotides Z, P, S, and B). There are LOTS of potential implications from this - from the spread of artificial DNA, to the possibility of new life forms, and the potential therapeutic uses of new forms of DNA. One of the more intriguing possibilities is the expanded possibility for use of DNA as a storage molecule. Computer scientists and bioengineers have long been testing methods for using DNA as a way to store digital information (after all, evolution has refined DNA structure/function for a long time, to the point at which it is highly efficient and reliable). Having additional base pairs is akin to adding letters to our alphabet - it makes the number of words or combinations of bases much, much greater, and it dramatically raises the density of data which could be stored by a molecule of DNA.. There are lots of details to work out, but this is a scientific breakthrough that will be a top contender for 'science advance of the year', if not the decade - and you can say that you are well-informed about it! https://www.the-scientist.com/news-opinion/dnas-coding-power-doubled-65499 Hope that your Break is a good one! Dr. Nealen Hello everyone, In science education, we like to categorize - things are either "this way", or "that way". Simplifying the variety and pointing out the differences is a proven way to aid understanding, and "boiling things down" to their general features is usually also scientifically accurate - except when it isn't. In our labs this term, we have talked about meiosis and chromosomes, how chromosomes are paired to give us our genotype, how genotype determines what gametes can be passed on, and how our alleles direct our phenotype. Much of those discussions, as is typical, are of a 'this-of-that' format - we either have this genotype or that one, this phenotype or that one. But exceptions to these general rules are interesting, and often enlightening. Several weeks ago I sent you a news story about a bird that was spotted in Erie, PA that appeared to be a gynandromorph - a genetic mosaic of both male and female tissues. Gynandromorphs are rare, and form when something other than the normal pattern of gamete combinations, chromosome sorting, and cell division occurs during early embryonic formation. This week, there is news of another, even rarer genetic variant, this time in humans: a semi-identical pair of twins. You are already familiar with identical twins, which form when a fertilized zygote splits into two genetically-equal cells that develop into separate individuals. Identical twins share 100% of their DNA. You also know about fraternal twins, formed when two (separate) fertilized eggs, rather than one, develop at the same time. Fraternal twins share 50% of their DNA (on average), just like any two siblings born at different times from the same parents. In this, case we have something different. Semi-identical (sesquizygotic) twins form when a single female egg is fertilized by not one, but two, male sperm. This early embryo divides and begins to develop into not one fetus, but two fetuses. These fetuses develop at the same time and are born as twins. In this case, though, they are predicted to share 75% of their DNA, because they share 100% of their mother's DNA and only 50% (on average) of their fathers DNA, which together average 75%. In the case reported here, the twins share a slightly higher value (89%). It is likely that this unusual pattern of fertilization actually happens with some frequency, but that the early embryos do not typically survive. This chance occurrence will give geneticists a new data point in their ability to test hypotheses of genes and relatedness - no longer are all twins in their databases either 50% or 100% related, now there is a known 3rd possibility. https://www.bbc.com/news/health-47371431 Have a great weekend - Dr. Nealen Good morning all, Our lab topics remain at the forefront of science news: this week, Japanese scientists announced a new stem cell therapy for treatment of spinal cord injuries. In lab this past week, we considered both stem cells as well as genes related to the spinal column - together, these are evidence that very basic studies of individual genes can often lead to useful results! And, we will talk more about this specific kind of stem cells (induced pluripotent stem cells) in an upcoming lab... https://www.the-scientist.com/news-opinion/japan-approves-ips-cell-therapy-trial-for-spinal-cord-injury-65484 Have a great weekend - Dr. Nealen Good morning all, In our labs these past two weeks, we have explored the shuffling of chromosomes that occurs during meiosis, and how the alleles of the genes on the chromosomes get sorted into gametes, which then combine to give offspring unique genotypes (sets of chromosomes and alleles) and phenotypes (physical features). Some of our examples this week included our 'sex chromosomes', the X and the Y, which combine to give us female (XX) or male (XY) characteristics. When we discussed the phenomenon of nondisjunction, we noted that sometimes things don't quite work according to plan, and that unusual chromosome numbers occur. How about when unusual chromosome combinations occur? You may have seen a news story recently abut an unusual bird (spotted in Erie, PA) that appeared to be male on one side of its body and female on the other. This is likely to be a gynandromorph, an individual that has male chromosomes (genotype) and characteristics (phenotype) on one side, and female genotype and phenotype on the other side. A few examples of gynandromorphy have been reported in animals over the years. They appear relatively normal (as male and female organs are generally the same), but their ability to mate and breed is likely very low (as male and female mating behaviors and reproductive structures are very different, of course). This individual was spotted because, in this species (the Northern cardinal), male and female phenotypes are very obviously different in color (dimorphic). In most bird species, you can't tell females and males apart, as they look the same (monomorphic). It makes me wonder: how many gynandromorphs are out there, and we just don't know about them? And, does this occur in humans? https://www.nationalgeographic.com/animals/2019/01/half-male-half-female-cardinal-pennsylvania/ Have a great weekend - Dr. Nealen Good morning, When we met for our first class, I ave you a survey asking about some of the science topics that you find interesting, and the idea of 'personalized genetics' came up in a number of your responses. We'll tackle aspects of this issue several times this semester. Today, I am passing along a link to a news article about the use of unexpected sharing of personalized genetic databases with law enforcement agencies. While there is the potential for much good to come from this sort of exchange, it also raises some concerns, especially as it does not align with the reason that most people seek out their genetic background. This problem will be good fodder for our discussions... https://www.sciencenews.org/article/family-tree-dna-sharing-genetic-data-police-privacy Have a great weekend - Dr. Nealen |
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