Movie- The Ghost In Your Genes.docx

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Department
Biological Sciences
Course
BIOC14H3
Professor
Patrick Mc Gowan
Semester
Winter

Description
Movie: The Ghost In Your Genes  We are at the brink of uncovering a hidden world, a world that connects the past and future generation in ways we didn’t imagine before o Environmental exposure the genes that you grandmother has could cause a disease in you (even without exposure to toxin) and you will pass to grandkids o Discoveries have potential to affect lives and environment in early life of ancestor you are what you eat but you are what your parents are and grandparents and stress of grandmother and grandfather  Science of inheritance turned in its head and we are changing view of what inheritance is  Swedish town- Evidence for medical revolution in the edge of the Artic circle - remote area cut off from most of world’s history and Pembry came here to met colleague Begen and story in grave yard hold proof to radical ideas and these people can contribute and see changes in ways we think of inheritance  Find grandmothers and daughters and grandfather and grandsons connect people 100 years apart in new ways and uncovering links that confound scientific thinking  Inheritance is just the genes and DNA sequences and want to demonstrates inheritance is more than that and a combination of more than 20 years of work and the first time Pembry is confronting the magnitude of discovery  Marcus Pembry is one of a select band scientist who wants to challenge an orthodoxy and they believe that the lives of our parents and grandparents affect our wellbeing despite never experiencing these things ourselves  To many these ideas is regarded as a scientific herecy o you cannot predict what the important discoveries will be and the only thing you can do is follow your instinct  Conventional biology – believed genetic inheritance set in stone in the moment of conception– and at that instant we inherit a set of chromosomes from mother and father and within the chromosomes are genes strips of coded DNA the basic unit of inheritance and after conception the genes are locked away in the cells body and protected and untouched by the way you live (what you do affects you but genes remained untouched)  Classic genetics – parents and grandparents just pass on genes and experiences accumulated in life time are never inherited lost forever as the genes remain untouched from generation to generation  Biology of inheritance was a reassuringly pure process  Early 80s Marcus Pembry headed clinical genetics department for children- Treating families with abnormal genetic conditions coming across families that didn’t fit rules/patterns that genetics are suppose to fit so think of chromosome abnormalities but check the chromosomes and they are normal  So have to start imagine and what underlies this and driven to work it out since families need help – the more families seen more rules of inheritance broke down – diseases didn’t fit with textbook conventions  One condition in particular caught his eye called Angelmann syndrome – referred to them as happy puppet children and have a rather jerky movement when walking and children have no speech and severely incapacitated when learning and always happy and smiling all the time o Caused by genetic fault and the key sequence of DNA was missing from chromosome 15  Then Came across paradox – at the Same time same change and deletion clearly associated with a different syndrome much milder in terms of intellectual impairment, the Prader-Willi syndrome – floppy at birth, when eating properly at birth have an insatiable appetite and grew very large o What pembry saw was two completely different diseases caused by same genetic fault  Simple view of inheritance was beginning to unravel but doubts were contradictory to the scientific community  In early 1990s the biggest project in biology captivated in the world ( was seen as the greatest achievement of the history of mankind) o the human genome project pinnacle to the century of work on genes and genetics and seemed that the secrets to life were at our fingertips o Genetic blue printing of life/Mapping out maybe human genetic code/ Set of instructions to make a human being  like a bible were everything was written down and hope is once we have in front of us the letters we read down pages and we would understand how body was put together  Have a complete understanding of human biology at the molecular level and hope was that scientist would find the cure for every disease (leading to the end of diseases cancer/AD parkinson’s diabetes) o thinking of genes in a chemical way in the term sequence of letters (work out letters in book) - human genome contains 100,000 genes and when they started sequencing found it went down to 60K then to 50K and down to a much smaller number and found that the human genome is not as complex and don’t as much genes as plants do and now question if our genome has less genes than this species and we are more complex potentially what is going on here o and now scientist estimate we have probably less than 30,000 genes  Believed that we would be able to find the genetic components of common diseases – and proven to be very difficult, the idea of 1 gene one disease doesn’t explain it all o Humans have about 30000 genes and this doesn’t explain human complexity so it had to be something they missed  First hints of what was missing was in the paradox of PW and AS – two different diseases caused by the same genetic fault o when Pembry look at the inheritance patterns he saw something stranger and what really mattered is the origin of chromosome 15 that had the deletion  if the deletion was on chromosome 15 that the child inherited from the father then you would have Prader-Willi and deletion was inherited from the mother you would have the Angelman syndrome o Was a surprise that the same strip of DNA causes one syndrome when it came from the father and completely different disease when it came from the mother and as if the genes knew where it came from o If you have a developing fetus manifest this condition, how does the chromosome 15 know where they came from? Must have been a tag/imprint placed on chromosome joining either egg or sperm from previous generation that came from the mother and father and were functioning differently key thing that although DNA sequence are the same the different sets of genes were being silenced whether it is from mother or father  it showed that there was more to inheritance than the coding sequence of DNA. We then realize we are dealing with genomic imprinting and what genomic imprinting is that genes have a memory of where they came from and something other than DNA was capable of moving between generations  a glimpse of the world and a hidden layer that controls how our genes function and inheritance is not only about which genes are inherited but which genes are silenced switched on or off and like a light switch, switch on the gene the light is shining the gene is active and makes cell do a certain thing and the light switch is off everything is dark the gene is off and the switches remains on or off and gives the cell an identity  and the activity of genes was being controlled by a switch and attachment of a chemical that dictates when a switch is on or off o whether genes turned on or off is epigenetics  not only is the sequence of DNA important in addition there is overlying epigenetics that allows the genes to turn on or off and epigenetics explains why a humans can be created with less than 30,000 genes and how the human genome project didn’t give us all the answers  Now if we put epigentics on top of it is more complicated in terms of whether genes are activated to a certain level then we have complexity that explains biology much more effectively than the simple sequence of DNA o now we have additional levels of complexity that we need to understand that are well beyond the sequences of DNA o the next huge challenge for modern biology is to decipher the epigenetic code and understand all the combinations of switches that exists o an accurate chemical map of the genome tells little how it works and transcribing the code of the genes of the genome project is not an end but simply a beginning  if inheritance not just about DNA and if switches important just what turns them on or off  Stephanie – pregnant and doctors recommended ivf treatment and in the UK around 8000 babies are conceived every year using reproductive techniques like ivf treatment are and after 3 attempt become pregnant and they didn’t really highlight risk o Went for a routine scan and scan was taken for a long time and found exopholus and part of the bowel is on the outside of the abdomen and doctors suspected suffers from bv syndrome where babies are large and oversized tongues and high risk of developing childhood cancers o They couldn’t say 100% certain that he has this condition but saw his tongue protruding and on the scan they said he has big thighs and didn’t know how severely affected he was o when he was born was clear that he indeed had bv syndrome - Within a few hours did surgery for bowel outside to put it inside and also had surgery to reduce size of tongue and did scans to check for tumors monthly  Cases of bv syndrome caught the attention of Wolf wright- worked in developmental genetics and was fascinated by the epigenetic ghost world o wanted to know what could throw switch on or off and found placing mouse embryo in a cultured dish to trigger genes to switches off and found relatively easy to change switches in mouse embryo the same could also be true in human embryo o in ivf treatment you have an embryo for a brief period of time in a cultured dish and were asking the question in the mouse embryo the mere fact of human embryos in a cultured dish or being manipulated could alter their epigenetic switches  Wright knew that bv syndrome was caused by a faulty switch and looked at babies children with bv o what proportion were conceived with ivf and could ivf treatment switching genes on or off or cause syndrome o we see an increased occurrence of bv syndrome in the ivf population and although the disease risk increased 3-4X with ivf treatment removing the embryo from natural environment could triggers disease o Look at ivf procedures conditions used and carry out more precise experiments too see how we can avoid throwing these epigenetics switches o Wright showed a simple change in environment is enough for turning gene on or off  Any altered switches could not be inherited and took some mice with altered gene sequences and bred them and expectation was that as the altered genome was passed to children the epigenetic changes would be wiped clean o looked at profile of offspring and was amazed and have dots and dots means a gene is on and the epigenetics switch in one gene is present in second generations  this meant the Genes not locked away and simple environment affect how genes worked and that could be inherited and as if a memory of an event passed down through generations o scientists regarded this as impossible and if seen in humans implications were profound so what we experience could affect our children and grandchildren  Pembry- Why link between generations would exist and speculated outside main career and speculated why genes would carried memory from one generation to the next, what evolutionary purpose it served and imprinting was used to for some sort of transgenerational adaption  thought it could be used for a mother to send messages to baby in the next generation and question was what stops the baby’s head jamming in the head canal o e.g. Mother was starving small pelvis maybe egg captured that information and were instructing babies not to too grow and jam up birth canal so there was some sort of coordination between the 2 generations but there was no evidence and pure speculation. 
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