Posted on 01/23/2014 4:12:45 AM PST by Kaslin
My mother's father died of cancer before I was born. My mother was pregnant with me, but had not told her father that she was to have a second child. The story I've been told is that they opened him up to remove the cancer -- and found it everywhere. They closed him back up and sent him home to die.
Both of my mother's brothers died of cancer. All three of these men were heavy smokers, one ignored the signs of potential trouble for years, and all three died from cancer.
My mother was diagnosed with cancer in 1978 and beat it. She was diagnosed a second time in 2005, but again beat cancer. She went to heaven last fall, but not due to cancer. She was not a smoker -- so what was the cause?
Her sister, my aunt, has never had cancer. I've often wondered, what genetics, lifestyles and triggers can make a difference in the cause of cancer?
There are some scientific discoveries so mind blowing that when you first hear about them you know that they are really, really big. That there will be ramifications for decades, even though you don't know what the ramifications will be.
The grandness of the discovery captures your imagination and changes your thoughts about relationships and life, even thought you don't quite understand the details, the underpinnings of the discovery.
Such is the discovery noted in The New York Times article this week, "Seeing X Chromosomes in a New Light," by Carl Zimmer. The article captured my imagination and broadened my mind.
The last time that I dealt with chromosomes was in college biology, when I had the mistaken belief that biology was my future and my major. A few chemistry labs later and one histology class, and I knew that my future was not in biology, but in business, where getting an A did not involve donning goggles and aprons for hours at a time.
As a quick review, the female chromosomes are XX and males are XY. Children receive one of their mother's X-chromosomes and either the X, or Y-chromosome from their father. The transmission of the father's chromosome determines whether the child is a male or female. This is not new news, but old.
Females, having two X-chromosomes, shut down one of the chromosomes at a cellular level. Which X-chromosome is shut down varies by cell -- in some it's the one passed down by the father, in others it's the chromosome that is passed down by the mother.
OK -- so scientists have known about this for over five decades, and it's just now coming to my attention -- but why the press now?
A recent study was published in "Neuron," that included maps of the X-chromosome inactivation. "They found a remarkable complexity to the pattern in which the chromosomes were switched on and off," according to Zimmer.
Females have two copies of the X-chromosome, each of which has different versions of the genes not found on the other. This allows for one or the other to be used in the cell, leading to more genetic diversity than males. If one of the genes has a weakness -- the other can be used.
"Females simply have access to realms of biology that males do not have," Huntington Willard, the director of Duke University's institute of Genome Sciences & Policy noted.
The recent published research led by Dr. Nathans showed illuminated maps of where different X-chromosomes were activated in various cells within the bodies of mice. Nathans "speculates that using chromosomes from both parents is especially useful in the nervous system. It could create more ways to process information. 'Diversity in the brain is the name of the game.'"
What shuts down the second X-chromosome? It's a number of molecules, led by what has been named the Xist.
Dr. Lee, a Howard Hughes Medical Institute investigator at Harvard Medical School, has found that when the Xist is inactivated and the second X-chromosome is allowed to be active, it creates extra proteins. These extra proteins can drive a cell to grow uncontrollably. This additional uncontrollable growth makes cancer is more likely.
Women's brains are created differently, on the molecular, cellular level. What does this mean? I'm not sure, but I'm fascinated. Now that we know Xist exists, maybe we can determine how it becomes inactive -- and ensure it remains inactive.
To me, this new research is both mind-blowing and potentially life-saving.
Add on top of that that humans are a diploid species. Each of our 23 chromosomes have a duplicate backup copy in the cell giving us a total of 46.
My mother has survived breast cancer twice now.
Congratulations to your mother
She just turned 81.
Seen a show on the science channel and it touched on this. It also stated that the Y is prone to “corruption” when it replicates, which is the reason males are more prone to genetic diseases.
Yes, some real interesting research going on in genetics..
Anyone who is curious about the patterns of X inactivation can learn about it by looking at a calico or tortoiseshell cat. In cats, the coat color genes are carried on the X chromosome. So a calico or tortoiseshell cat has one X with a black coat gene, and the other X with an orange coat gene. How varied the pattern of orange and black is, and how large the patches are, depend on when during development the extra X chromosome was switched off. If a specific X chromosome is turned off early in development, the resulting solid color patch will be larger than if it was turned off late.
What shuts down the second X-chromosome? It's a number of molecules, led by what has been named the Xist.
Dr. Lee, a Howard Hughes Medical Institute investigator at Harvard Medical School, has found that when the Xist is inactivated and the second X-chromosome is allowed to be active, it creates extra proteins. These extra proteins can drive a cell to grow uncontrollably. This additional uncontrollable growth makes cancer is more likely.
Women's brains are created differently, on the molecular, cellular level. What does this mean? I'm not sure, but I'm fascinated. Now that we know Xist exists, maybe we can determine how it becomes inactive -- and ensure it remains inactive.
This is *not* the entire story on cancer. It is only one small clue. The deactivation of Xist may be a consequence of the carcinogenic process, and not a driver of it. Cancer is multifaceted, and many genes and processes have been identified that contribute to it. Viruses cause cancer, as do certain chemical exposures, strong radiation exposures (including exposure to sunlight), and even random mutations. There is not a simple answer with a simple fix out there waiting to be discovered.
Thanks for posting.
My mother died 1-1/2 years ago. She had visible hardening Amyloid Protein deposits in here facial tissue. She had lung cancer, went through chemo, died of heart failure. She had some form of dementia. (not all dementia is Alzheimers)
They had treated her with drugs to enhance the pumping of her heart. We have thought that protein deposits in her heart tissue may have caused hear death. Her oxygen level dropped due to poor circulation of blood, not lung capacity.
I did not know about the dual X-chromosomes in women.
In my mind, one of the most ignored aspects of cancer is cancer cell nutrition. Most cancers are essentially failures in the cell’s energy metabolism. Cancer cells’ mitochondria malfunction, and they lose the ability to metabolize fatty acids. So they feed exclusively on glucose.
That’s why PET scans work - they inject a radioactive glucose into the body, and detect the gamma rays it emits. A disproportionate proportion of this glucose is absorbed into cancer cells.
The question is, if most cancer cells can feed only on glucose, would it not be an effective adjunct to cancer treatment to keep blood sugars low? In other words, to put the patient on a low-carbohydrate, ketogenic diet?
There have only been a very few studies on this, but the results look promising. (The biggest problem is that there isn’t any way for the pharmaceutical companies to profit from dietary protocols, so there’s little grant money available).
This is *not* the entire story on cancer. It is only one small clue.
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I was unable to find the section in the article wherein it was suggested that this *was* the entire story on cancer.
Like you say, it’s one more clue, one more step in the direction of understanding the disease.
I count that as a good thing, don’t you?
Well, ... sort of.
Just as the two X chromosomes which each female has are not identical, so too the other pairs of chromosomes do not consist of identical information. Genetic diseases can occur when one or both of such pairs are defective.
For those whose education in genetics was imparted in the 1960s, as mine was, it may come as a surprise that the simplistic models used at the time were not correct in some very interesting ways.
I was taught that half of my chromosomes came from my father and half from my mother. The simple model was that the sperm cell contained a random selection of one-half of each pair of my fathers chromosomes. It's evidently more complicated than that.
At the time that sperm cells are formed, each pair of a males chromosomes separate and only one half of each pair goes to a particular sperm cell.
The complication that wasn't known at the time is that there is another random distribution of material that goes on when the pairs separate. The two chromosomes in each pair can exchange information on a level below that of a complete chromosome. I believe that the same process occurs during the formation of the human egg cells.
The simplistic picture I had from years ago was that exactly half of my chromosomes were identical to 23 chromosomes in my father and the other 23 were identical to 23 chromosomes in my mother. Due to this mechanism of chromosomes exchanging information, this is evidently not true.
If there's a geneticist among us, I would be eager to hear more information about this and any consequences that such a mechanism might have.
You are correct, and I realized I simplified things after posting it.
Part of them come from the mother and part of them come from the father - as you say, sort of.
Even amongst and individual chromosome, part can be from either parent. That was I think the reason that gal won the Nobel prize way back over a sort of “genetic drift” or jumping genes.
Something I found totally fascinating was that recently, there was a woman with some kind of brain disease. They ran genetic testing on her and almost fell over, because they hit on a set of genes that weren’t even hers. In fact, they weren’t even female!
But they were a perfect match for one of her sons!
Seems during pregnancy, some of the childs cells can go the other way across the placenta!
Astounding finding, IMHO.
Would seem to me to be the other way around, since females do not have a Y chromosome. More explanation is clearly needed.
Actually, I'm not aware that any part of a particular chromosome can come from different parents. The process I was describing was that of a swap of parts between two paired chromosomes in the father, during meiosis I think it's called. Or, similarly, the swap of parts between two paired chromosomes in the mother.
Any other "jumping" is news to me.
Even more astounding, I think, than an pre-born infant's cells migrating across the placenta is a case I recall from somewhere in Europe.
According to Wikipedia, a mother and her children were given DNA tests in a suit to deny her public assistance.
The astounding result was that the woman was not the "biological mother" of any of her children. This was despite witnesses to the childrens' births.
The solution, long in coming and after considerable disruption to many lives, turned out to be that the mother was a "chimera". That is, some parts of her body had one DNA profile and other parts a completely different profile.
The woman's reproductive system had DNA different from the tissues from which the samples were taken for testing.
Given the oddities in how the other 22 pairs of chromosomes behave, I would agree, since 96% of the chromosomes (22 /23rds) behave the same.
Then there's the mitochondrial DNA which is only passed to an individual through the mother, which only further complicates an already very complicated issue.
I'm not a geneticist, but a biochemist/molecular biologist. Which means that I know all about the chemistry of biomolecules.
The exchange of genetic information between pairs of homologous chromosomes happens during formation of both male and female gametes. The only chromosome that does not exchange genetic information is the Y chromosome. As a result, the X and Y chromosomes that end up in the sperm are identical to the X and Y chromosomes the man inherited from his parents. Other than the X or Y chromosome contributed by the father, NO chromosome in a child is like any of their parents' chromosomes.
The exchange of genetic material between homologous chromosomes leads to such effects as duplicated or deleted genes or parts of genes, and even whole chromosome arms being deleted or duplicated. On occasion, it can cause chromosomes to be fused or broken apart; one evolutionary difference between humans and chimps is a difference in chromosome number, caused by a fusion or breaking event. When large sections of chromosomes are deleted or duplicated, the effects can be drastic. If a gamete containing such a defect fuses with another gamete during fertilization, and the fertilized egg grows, the missing or excess genes typically cause severe growth problems in the fetus, usually ending in death. Only a couple of chromosome duplications are survivable--trisomy 21 (Downs syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). Downs syndrome is the least deleterious and most survivable of these conditions; most trisomy 18 and 13 babies die within days or weeks after birth.
One other source of genetic material is the mitochondria. The mitochondria, being a bacterium, has its own chromosome. All children receive mitochondria from their mothers; hence, the mitochondrial DNA is identical to that of their mothers.
Anyway, I think that is enough information to throw at you at one time. If you have specific questions, I will be glad to answer!
I was commenting (indirectly) on the author's "golly gee" attitude, which I see too often in reporting of medical matters.
Yes, this is another clue to understanding at least some cancers. Many such clues are revealed all the time. We have a long way to go before we understand everything about cancer.
What is the definition of "bacterium" that applies to mitochondrial DNA? Being an integral part of (most?) human cells, how can it be referred to as a "bacterium"?
Also, how much information has been developed about the "exchange of genetic information"? What is known about the mechanism?
Watson and Crick realized that the C and T were complementary to the G and A nucleotides and that this suggested a means for replication. It would seem that some of the coding constitute markers for delineating the extent of exchangeable sections of the chromosome. Is any of this understood yet?
Thanks for the clarifications. It's handy having a molecular biologist available. But then you've probably heard that before.
Some more interesting conversation on this thread, too.
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The mitochondria of all eukaryotic cells, and the chloroplasts of plant cells, are both remnants of early bacteria that formed a symbiotic relationship with a larger unicellular organism. I do not know what kind of bacteria the chloroplast is, but there is evidence that the mitochondria are a type of rickettsia. (Note: other species of rickettsia (spread by ticks) are obligate intracellular parasites that can cause severe disease.) The mitochondrial chromosome has all the characteristics of a bacterial chromosome--it is circular, it contains no introns, and most of the DNA is coding (that is, it transcribes directly into message RNA for protein production). In addition, the mitochondrial DNA uses a slightly different triplet code than the nuclear DNA. Many of the mitochondrial genes have been integrated into the nuclear DNA (DNA tends to move around) over the course of evolution. At this point, the mitochondrial are absolutely incapable of independent living. We also cannot live without them.
Another interesting tidbit is that we also have thousands of viruses living in our genome. In some cases, we are dependent on those viruses--a protein necessary for placental development actually is encoded in a virus! A few years ago, I read about some researchers who were reconstituting one of those viruses from the information in our genome. Since they did not know what the virus might do, they did all this work in high biocontainment. Right now, koalas are being infected by a retrovirus that appears to be making itself a permanent part of their genome. The last such event in humans probably took place over 100,000 years ago.
Also, how much information has been developed about the "exchange of genetic information"? What is known about the mechanism?
Watson and Crick realized that the C and T were complementary to the G and A nucleotides and that this suggested a means for replication. It would seem that some of the coding constitute markers for delineating the extent of exchangeable sections of the chromosome. Is any of this understood yet?
There are several mechanisms for genetic information exchange. One is the crossing-over that happens during gametogenesis. I won't talk about all of the mechanisms, but I will discuss one discovered by my hero, Dr. Barbara McClintock. She is my hero because people didn't believe her research was valid, and they were mean to her (in the scientific way, meaning they used big words to insult her), yet she persevered with her work and eventually won the Nobel Prize. What happens is that little pieces of DNA excise themselves from the chromosome and insert themselves somewhere else, either in the same chromosome or a different one. There are enzymes involved that facilitate this process. This system uses the fact that some DNA sequences are repeated throughout the genome; it inserts and removes itself wherever it finds a matching sequence. These transposons, as they are called, can disrupt gene function if they insert themselves into the gene's control region. In corn--the system that McClintock studied--the action of transposons causes the colors of kernels on the same ear to be different. This is especially noticeable in "Indian corn." When a transposon inserts itself into the pigment gene in the germ cell, the resulting kernel is white. All eukaryotes, including humans, have transposons, and those transposons are (IIRC) always moving around.
And, in answer to your question, I will say that yes, quite a bit is understood about how DNA is exchanged between chromosomes. Homologous chromosomes line themselves up on the basis of matching DNA sequences. Hmm, I will have to cut the explanation short, partly because I must go to work, and partly because this explanation really needs pictures.
Thanks for the clarifications. It's handy having a molecular biologist available. But then you've probably heard that before.
Thank you!
:)
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