Embarrassing as it might be to admit, I forgot how to do dihybrid crosses between freshmen year and now. I did not find the book to be particularly helpful in explaining this, so I found this video:
He uses traits in mice, the grasshopper phenotype and the prune phenotype, to set up a cross. I particularly liked how he explained what happened if the genes were linked (on the same chromosome) and if they were independently assorted. I also liked how he used the pictures of chromosomes to really explain how these crosses occur, very similar to what Dr. Weber did in class. Later on in the video, he goes through what happens when two genes are linked, using a CSP (craniofacial and skeletal malfunction) phenotype that is on the same chromosome as the grasshopper phenotype. He uses the appropriate terminology throughout the video and I appreciated his use of the terms "parental" and "recombinant". Sometimes, Youtube video makers are rather incompetent when it comes to terminology, but thankfully he is not! He also briefly touches on the probability aspects of dihybrid crosses. I also learned something new when at the end of the video he talked about map units and what they measure. The last think I liked about his explanation was how he explained the proper way to write the genotype of the mouse, with regards to the linkages of the genes.
Tuesday, February 21, 2012
Diseases for Darwinism
This article discusses Huntington's disease, what causes it, and the other effects that having this disease can have besides the classic symptoms. Huntington's disease is a neurological disorder that destroys neurons in certain regions of the brain. This causes the patient to have difficulty controlling movements. This can lead to various cognitive and emotional problem. This disease occurs due to a mutation that leads to the abnormal elongation of a gene known as huntingtin. The length of this gene becomes problematic when it exceeds past a certain extent and the length has an impact on the severity of symptoms.
Animals with this type of mutation only develop Huntington's when they make p53 (the tumor suppressor we learned about in Chapter 14!). Studies at Tufts University have found that people with Huntington's disease are less likely to have cancer and have more children than the average person. It is possible that increased p53 plays a role in these "side effects" of Huntington's. This is because, as we have previously learned, p53 regulates cell division and helps prevent cancers. The article goes on to talk a little bit more about p53 and its link to Huntington's. However, I want to get more into the material that is related to Chapter 16. As we know, Chapter 16 is about simple patterns of inheritance. As we have also learned in class, Huntington's disease is autosomal dominant. Look at this nifty picture to see how this disease is passed down generations:
The mutated gene is located on an autosomal (non-sex) chromosome and a person needs only one copy of the mutated gene for them to express the disease. As you can see in the picture above, the father is heterozygous for Huntington's but expresses the disease since it is dominant. Because he has children with a normal woman, 50% of his kids are unaffected while the other 50% are affected. I retrieved this infromation from here. If you are curious about Huntington's this site is extremely reliable and has a brief overview of the disease as well as detailed explanations.
The information in the previous paragraph is mostly review (since we have discussed the autosomal dominant nature of Huntington's in class), and I would also like to discuss another aspect of the Scientific American article that relates to our current chapter. A biologist at Tufts, Philip Starks, who has been studying p53 and Huntington's (as mentioned before) suspects that Huntington's is an example of antagonistic pleiotropy. Pleiotropy is when a mutation in a single gene results in multiple effects on the individual's phenotype. There are several forms of pleiotropy. One is when a single gene expression can alter cell function in more than one way. Another is when different cell types express a gene within a multicellular organism. Finally, one gene may be expressed at different phases of development. Check out pg. 343 in our biology textbook for even more information regarding pleiotropy. Starks believes that Huntington's may be pleiotropic because the same protein that results in the debilitating symptoms of Huntington's may also be responsible for making Huntington's patients more reproductively successful.
Animals with this type of mutation only develop Huntington's when they make p53 (the tumor suppressor we learned about in Chapter 14!). Studies at Tufts University have found that people with Huntington's disease are less likely to have cancer and have more children than the average person. It is possible that increased p53 plays a role in these "side effects" of Huntington's. This is because, as we have previously learned, p53 regulates cell division and helps prevent cancers. The article goes on to talk a little bit more about p53 and its link to Huntington's. However, I want to get more into the material that is related to Chapter 16. As we know, Chapter 16 is about simple patterns of inheritance. As we have also learned in class, Huntington's disease is autosomal dominant. Look at this nifty picture to see how this disease is passed down generations:
The mutated gene is located on an autosomal (non-sex) chromosome and a person needs only one copy of the mutated gene for them to express the disease. As you can see in the picture above, the father is heterozygous for Huntington's but expresses the disease since it is dominant. Because he has children with a normal woman, 50% of his kids are unaffected while the other 50% are affected. I retrieved this infromation from here. If you are curious about Huntington's this site is extremely reliable and has a brief overview of the disease as well as detailed explanations.
The information in the previous paragraph is mostly review (since we have discussed the autosomal dominant nature of Huntington's in class), and I would also like to discuss another aspect of the Scientific American article that relates to our current chapter. A biologist at Tufts, Philip Starks, who has been studying p53 and Huntington's (as mentioned before) suspects that Huntington's is an example of antagonistic pleiotropy. Pleiotropy is when a mutation in a single gene results in multiple effects on the individual's phenotype. There are several forms of pleiotropy. One is when a single gene expression can alter cell function in more than one way. Another is when different cell types express a gene within a multicellular organism. Finally, one gene may be expressed at different phases of development. Check out pg. 343 in our biology textbook for even more information regarding pleiotropy. Starks believes that Huntington's may be pleiotropic because the same protein that results in the debilitating symptoms of Huntington's may also be responsible for making Huntington's patients more reproductively successful.
Monday, February 20, 2012
Gene Therapy and X-Linked SCID
In class this week, we learned about various patterns of inheritance. These included simple Mendelian inhertiance, incomplete dominance, codominace, sex-influenced inheritance, and X-linked inheritance. For this blog post, I am focusing on the last of these types of inheritance patterns.
X-linked severe combined immunodeficiency, or SCID, is a disease that causes people to not have functioning immune systems, leaving them susceptible to life-threatening infections. This disease results from a lack of T cells and natural killer cells as well as nonfunctional B lymhocytes (remember these from A&P?). Children with this disease are usually diagnosed to the recurrence of infections despite normal treatment. The final diagnosis of X-SCID is done by checking lymphocyte counts, lymphocyte functionality tests, and testing of the molecular genes. The best treatment for SCID is a bone marrow transplant from a genetically matched sibling. In the absence of such a sibling, unmatched donors are often recruited to donate bone marrow although these transplants are only about 70 percent successful.
As seen in the name of the disease, the inheritance of this condition is X-linked. This condition is more likely to occur in males, since they only have one X chromosome. Therefore, there is no recessive or dominant involved in their inheritance. In a female, it is possible to have recessive X-linked conditions that are not expressed due to the presence of normal genes on the other X chromosome. This is not an option for males, since they have an X chromosome and a Y chromosome. If a mother is a carrier for this disease, the chance of her transmitting this gene is 50%. Males who have SCID can only pass this gene on to their daughters, and not their sons. As we know from what we learned in class, this is because an X chromosome is contributed to daughters while a Y chromosome is contributed to sons. It is possibly for prenatal testing to be conducted on women to determine if they are carriers for this disease.
Feel free to read this article, from which I retrieved my information, to understand more about this disease. I mainly attempted to focus on the information that was relevant to our current chapter of patterns of inheritance.
X-linked severe combined immunodeficiency, or SCID, is a disease that causes people to not have functioning immune systems, leaving them susceptible to life-threatening infections. This disease results from a lack of T cells and natural killer cells as well as nonfunctional B lymhocytes (remember these from A&P?). Children with this disease are usually diagnosed to the recurrence of infections despite normal treatment. The final diagnosis of X-SCID is done by checking lymphocyte counts, lymphocyte functionality tests, and testing of the molecular genes. The best treatment for SCID is a bone marrow transplant from a genetically matched sibling. In the absence of such a sibling, unmatched donors are often recruited to donate bone marrow although these transplants are only about 70 percent successful.
As seen in the name of the disease, the inheritance of this condition is X-linked. This condition is more likely to occur in males, since they only have one X chromosome. Therefore, there is no recessive or dominant involved in their inheritance. In a female, it is possible to have recessive X-linked conditions that are not expressed due to the presence of normal genes on the other X chromosome. This is not an option for males, since they have an X chromosome and a Y chromosome. If a mother is a carrier for this disease, the chance of her transmitting this gene is 50%. Males who have SCID can only pass this gene on to their daughters, and not their sons. As we know from what we learned in class, this is because an X chromosome is contributed to daughters while a Y chromosome is contributed to sons. It is possibly for prenatal testing to be conducted on women to determine if they are carriers for this disease.
Feel free to read this article, from which I retrieved my information, to understand more about this disease. I mainly attempted to focus on the information that was relevant to our current chapter of patterns of inheritance.
Tuesday, February 14, 2012
Meiosis Video
I found this video useful because ever since freshmen year, I have had difficulty differentiating what to call "chromosomes", "sister chromatids", and "homologous chromosomes". Even Ms. Patil couldn't understand why I couldn't understand meiosis properly! And when Dr. Weber explained it, I understood it for about 5 minutes before once again I was confused. In a way, watching this brief video on meiosis helped me figure out these terms. While it does not go in depth, the video hits all the major points of meiosis. It goes from interphase through the second cytokinesis. It even mentions crossing over and how it occurs. My only complaint is that it does not mention how errors might occur during meiosis. Of course, one can always refer to my previous blog post for that!
As a quick addition, I would like you to view this image:
| Typical Sexual Cycle for Humans | Typical Sexual Cycle for Protists |
| and Other Animals | |
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Diploid Phase 
Haploid Phase that I retrieved from here. While its just a simple image, it clarified my confusion over what diploid-dominant and haploid-dominant species were. For some reason, the description in the book was somewhat confusing to me. Here, the image on the left displays the cell cycle of a diploid-dominant species while the image on the right displays the cell cycle of a haploi-dominant species.
Surprises in Cell Division
As promised, this summary as well as this article are shorter than those of my previous post. So, without further ado...
A research group at the California Institute of Technology has been able to capture the first three-dimensional image of cell whose nucleus is dividing in high resolution. A new method of cell slicing and imaging were used that allowed for the image to be obtained. While conventional electron microscopy involves much handling of the specimen prior to viewing, a technique called electron cryptomography, or ECT, was used trap the specimen in a more native manner, encasing it in a thin layer of ice. A limitation is that ECTs require the sample to be 500 nanometers thick at the most. The smallest known eukaryote was used and even that needed to be sliced carefully using a machine and a diamond knife.
Now that we know why what the researchers at CalTech did allowed them to capture the image while others previously could not, let's move on to the cell division aspect of this. I will refrain from going in depth regarding how mitosis works, as we discussed this quite thoroughly in class. During metaphase, the sister chromatids line up at the center of the nucleus, where they are held by microtubules in the form of a mitotic spindle. In most fungi, plants, and animals, more than one microtubule attach to each chromosome prior to the separation of the chromosome sets. In the image taken by the researchers at CalTech, a cell with 20 chromosomes is present, but only 10, somewhat incomplete microtubules were found. I was quite surprised when I read this because in all the pictures in our bio books and the pictures we drew in class, there was at least one kinetechore microtubule per sister chromatid set.
This is sort of how I have always pictured mitotic metaphase:
This leads to the question of how the sister chromatids separated. The researchers hypothesized that perhaps the chromosomes bundled up so that they could be separated by a fewer number of microtubules. Further studies using this slicing and imaging technique might lead to new discoveries in several kinds of cells, including human cells.
A research group at the California Institute of Technology has been able to capture the first three-dimensional image of cell whose nucleus is dividing in high resolution. A new method of cell slicing and imaging were used that allowed for the image to be obtained. While conventional electron microscopy involves much handling of the specimen prior to viewing, a technique called electron cryptomography, or ECT, was used trap the specimen in a more native manner, encasing it in a thin layer of ice. A limitation is that ECTs require the sample to be 500 nanometers thick at the most. The smallest known eukaryote was used and even that needed to be sliced carefully using a machine and a diamond knife.
Now that we know why what the researchers at CalTech did allowed them to capture the image while others previously could not, let's move on to the cell division aspect of this. I will refrain from going in depth regarding how mitosis works, as we discussed this quite thoroughly in class. During metaphase, the sister chromatids line up at the center of the nucleus, where they are held by microtubules in the form of a mitotic spindle. In most fungi, plants, and animals, more than one microtubule attach to each chromosome prior to the separation of the chromosome sets. In the image taken by the researchers at CalTech, a cell with 20 chromosomes is present, but only 10, somewhat incomplete microtubules were found. I was quite surprised when I read this because in all the pictures in our bio books and the pictures we drew in class, there was at least one kinetechore microtubule per sister chromatid set.
This is sort of how I have always pictured mitotic metaphase:
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| Note that I pictured it with one microtubule per sister chromatids |
 |
| The top image shows multiple microtubules per set while the bottom picture show the bundling of chromosomes idea that fits with the information found in the study Click here to view the article. |
Human Aneuploidy
In Chapter 15, we learned about mitosis, meiosis, and the eukaryotic cell cycle. One of the topics covered is how variation in chromosome numbers and chromosome set numbers can occur. These changes can have significant consequences. Aneuploidy is one form of chromosome number variation in which there is a change in how many particular chromosomes there are. Therefore, the sum of the chromosomes could be a number that is not a multiple of a set. Aneuploidy can lead to congential birth defects as well as miscarriage. Most aneuploidy occurs due to errors in maternal meiosis I, and increased maternal age has an impact on error rates. The term nondisjunction is used frequently during this article. In case you did not know, nondisjunction is when chromosomes fail to separate properly during cell division.
Aneuploidy is both "the leading cause of miscarriage" and "the leading cause of congential birth defects and mental retardation". Research has been conducted on whether or not particular meiotic defects can be connected to aneuploidy or infertility. Most studies have involved males, which is mostly irrelevant to the understanding of human aneuploidy. Pairing of chromosomes, synapsis, and recombination need to be observed as they occur in fetal ovarian tissue. This can be challenging, particularly because there are years separating when the cells are in prophase and when they divide. Studies have been conducted on female oocytes instead to determine if chromosomes are already "set-up to mal-segregate" at the appropriate time. Several groups have concluded that in human oocytes there are high levels of defects during synapsis. This is not enough information to conclude that these defects during prophase relate to human aneuploidy. It needs to be determined whether or not chromosomes that are known to exhibit nondisjunction are also more prone to defects in synapsis and recombination.
A type of aneuploidy that you have most likely heard of before is trisomy, or trisomy 21 in particular. This is also known as Down syndrome.
Recent studies on mice have attempted to recreate the nondisjunctional meisosis and recombinational defects that are present in humans. The oocytes of the offspring of two closely related mice were analyzed and it was discovered that meiotic nondisjunction increased due to disturbance in recombination. In another study, it was discovered that oocyte chiasmata are located closer to the telomeres when maternal age is higher than the norm. This caused the connections between homologous chromosomes to be lost more frequently. Mutations also play a role in improper segregation. Research in these areas has supported the idea that abnormalities during prophase (particularly during synapsis, recomination, and cohesion of sister chromatids) can cause errors during chromosome segregation. Extensive research has also been conducted on pre-disposing factors, such as environment and even in a chemical used during the manufacturing of plastics and resin.
The molecular background of meiotic nondisjunction has yet to be discovered, as are the reasons behind the increases in nondisjunction with increasing age. In order for this to occur, in vitro studies need to be used on meiosis, but we first have to produce gametes from stem cells. The collaboration between stem cell researchers and aneuploidy researchers may be beneficial. By looking at both fields, scientists may be able to generate in vitro systems that are capable of producing genetically normal eggs while also discovering why meiosis in human females is frequently faulty.
Click here to see where I found this resource. Click here to access the full article. Thanks for reading this unusually long article. I will make sure to make my next two posts a bit shorter to compensate!
Aneuploidy is both "the leading cause of miscarriage" and "the leading cause of congential birth defects and mental retardation". Research has been conducted on whether or not particular meiotic defects can be connected to aneuploidy or infertility. Most studies have involved males, which is mostly irrelevant to the understanding of human aneuploidy. Pairing of chromosomes, synapsis, and recombination need to be observed as they occur in fetal ovarian tissue. This can be challenging, particularly because there are years separating when the cells are in prophase and when they divide. Studies have been conducted on female oocytes instead to determine if chromosomes are already "set-up to mal-segregate" at the appropriate time. Several groups have concluded that in human oocytes there are high levels of defects during synapsis. This is not enough information to conclude that these defects during prophase relate to human aneuploidy. It needs to be determined whether or not chromosomes that are known to exhibit nondisjunction are also more prone to defects in synapsis and recombination.
A type of aneuploidy that you have most likely heard of before is trisomy, or trisomy 21 in particular. This is also known as Down syndrome.
 |
| A helpful image displaying aneuploidy caused by nondisjuncton |
Click here to see where I found this resource. Click here to access the full article. Thanks for reading this unusually long article. I will make sure to make my next two posts a bit shorter to compensate!
Thursday, February 9, 2012
Nucleotide Excision Repair
While we were talking about the types of repair in class, I was having difficulty picturing how the repair worked. This animation goes through the process of nucleotide excision repair, starting from when base damage is recognized and the multiprotein NER complex forms. Next, helicase unwinds the DNA and the complete complex is created. Afterwards, exonucleases cut the DNA and the fragment is excised. A repair synthesis complex is formed and new DNA is synthesized, which ligase binds to original DNA. After this, DNA returns to its normal configuration. Even though this is only a short animation, I found it useful just to help me picture how nucleotide excision repair worked.
While searching Youtube for actually useful material, I came across this:
Basically, this song is terrible but I found that it actually had accurate information on p53 and its actions as a tumor suppressor gene. The song explains how p53 can respond to genetic mutations and why it is important for the maintenance of "genome integrity". It also connects the topic to cancer, and how defects in p53 can lead to disease. So...just remember that "to keep your genome mutation free is the concentrated passion of p53!"
P.S. I may have posted this because its sorta stuck in my head now in all of its suckishness and I figured that I ought to inflict its damage upon someone else. I am such a philanthropist!
While searching Youtube for actually useful material, I came across this:
P.S. I may have posted this because its sorta stuck in my head now in all of its suckishness and I figured that I ought to inflict its damage upon someone else. I am such a philanthropist!
Secrets of a Salty Survivor
Well, one article on cancer is more than enough for me. An important part of our chapter was learning about DNA repair. DNA repair is necessary to minimize damage caused by mutations. There were several methods of DNA repair that we discussed in class, including direct repair, nucleotide excision repair, and methyl-directed mismatch repair. In this article, the author talks about a microbe called Halobacterium (pictured below) from the Dead Sea that has a highly developed DNA repair system.
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Research into this topic can potentially help protect astronauts from DNA damage that results from interplanetary space radiation. As we learned in class, DNA molecules are sensitive to radiation. According to a researcher studying Halobacterium, her research group fragmented the bacteria's DNA completely through radiation only to find that it had reassembled its chromosome to working condition in several hours. Um, whoa!
Naturally, Halobacteria live in the extremely salty conditions of the Dead Sea (which is actually a lake), where most sea life would find inhospitable. This is because the salt causes the DNA to become damaged and even die in normal organisms because the extreme saltiness would lead to the same lesions as those created by exposure to radiation. In a series of experiments funded by NASA, researchers subjected this bacteria to the most dangerous form of UV radiation, and 80% of the bacteria survived while other bacteria, such as E. coli, would have been completely obliterated.
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| Each dot represents a gene while the color of each dot represents the level of activity |
A DNA microarray (pictured above) was created to fully picture the response of Halobacteria to radiation. In response to radiation, a set of pre-created repair enzymes quickly began to repair the DNA, after which more repair enzymes were produced. This bacteria has several DNA repair mechanisms, some of which are similar to plant, animal, Archaeal, and other bacterial repair methods.
Studies such as these can help researchers determine how DNA repair functions in humans and how it could possible by enhanced.
Tumor-Suppressor Protein Helps Keep Breast-Cancer Protein at Bay
In Chapter 14, we have been learning about mutation, DNA repair, cancer, and the possible interconnection of the three. One of our topics was tumor-suppressor proteins, which code for proteins that fix DNA damage and down-regulate cell division, acting as inhibitors. This article talks about a protein coded for by a tumor-suppressor protein called BRCA1. This protein by keep ovarian and breast cancer at bay be preventing the transcription of repetitive DNA segments. It has long been known that there is a connection between defective BRCA1 and breast and ovarian cancer.
Researchers have been attempting to discover how BRCA1 could play a role in ceasing the cancerous activities of cells. A study was conducted by a research group on mice that lack the BRCA1 gene. They found the expected defects with DNA repair and cell cycle regulation in association with a non-functioning BRCA1 gene. In addition, they found that these cells are scarce in heterochromatic centers, which are areas of compacted, untranscribed DNA located by a chromosome's centromere. Rather, these areas were highly active and produced "satellite repeats", which are many RNA transcripts. BRCA1 proteins in normal cells keep these areas untranscribed by tagging histones with ubiquitin. When this was artificially added, the cells were able to recover.
Therefore, it was determined that BRCA1 proteins prevent genomic instability. It still remains to be discovered why BRCA1 is so specific to breast and ovarian cancer. Further research has shown that satellite repeats can be found in many types of tumor tissues, and there are most likely several factors that contribute to the inability to maintain heterochromatin. Studies also have yet to determine why people with a defective BRCA1 gene are more likely to get cancer initially, while it now know why tumors develop after BRCA1 becomes defective.
Researchers have been attempting to discover how BRCA1 could play a role in ceasing the cancerous activities of cells. A study was conducted by a research group on mice that lack the BRCA1 gene. They found the expected defects with DNA repair and cell cycle regulation in association with a non-functioning BRCA1 gene. In addition, they found that these cells are scarce in heterochromatic centers, which are areas of compacted, untranscribed DNA located by a chromosome's centromere. Rather, these areas were highly active and produced "satellite repeats", which are many RNA transcripts. BRCA1 proteins in normal cells keep these areas untranscribed by tagging histones with ubiquitin. When this was artificially added, the cells were able to recover.
Therefore, it was determined that BRCA1 proteins prevent genomic instability. It still remains to be discovered why BRCA1 is so specific to breast and ovarian cancer. Further research has shown that satellite repeats can be found in many types of tumor tissues, and there are most likely several factors that contribute to the inability to maintain heterochromatin. Studies also have yet to determine why people with a defective BRCA1 gene are more likely to get cancer initially, while it now know why tumors develop after BRCA1 becomes defective.
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