Genetic Defects

1. Genetic Defects By Jazib Gohar: Powerpoint designer Anosh Akbar: Researcher Iris Schwartz: Researcher, and Katya Gribkova: Inventor

2. What Are Genetic Defects ? Genetic disorders are genes of a baby are corrupted. They occur when recessive and/or dominant genes are passed down to the baby from generation to generation. A genetic disorder could also occur when a baby has too many, too little, or damaged chromosomes. A baby with a genetic disorder has a certain problem such as a disease that is either in its genes to pass down to their children, or genes that are visible like paralysis.

3. Kinds of Genetic Defects Autism Cleft Lip and Cleft Palate  Sickle cell disease Cystic Fibrosis Down Syndrome

4. Genetic Defects: The bad things they do Imagine a baby with a spine outside of its body. Imagine a baby with an opening in its lip. Did the baby hit itself very hard to receive these characteristics? No, believe it or not, genetic defects are the real causes of this. Genetic defects are abnormalities in a baby’s health particularly in its body’s function or structure. This is why the babies have mental or physical problems. Did you know? When babies are living their first year of life, genetic defects are the leading cause of death. Most babies experience a shortened life if they inherit a genetic defect. Most genetic defects cannot be stopped from happening in a baby. Babies are born with genetic defects because of genetic and environmental reasons or because of damaged or more than enough chromosomes which babies inherit from their parents. These genetic and environmental reasons impact how the baby is born and produce genetic defects. It’s pretty hard to believe that each year in the United States, 120,000 babies are born with genetic defects. Genetic defects affect 1 out of every 28 babies. Until a child grows, most genetic defects aren’t clear. Not all genetic defects can be visible through an ultrasound. Some of them are invisible or not able to be seen. Genetic defects have caused many babies to suffer and many parents to cry.

5. Genes in parents affect how babies are born. There is a 3 to 4% chance that parents will have a baby with a genetic defect. The percentage rises if the baby has a family history of genetic defects. If both parents are carriers to a certain disease, their child has a 25% chance to have the disease when born. There are recessive and dominant genes in everybody. For example, brown eyes are dominant over blue eyes. These genes determine how severe or if the baby will have the genetic defect. There are many different types of genetic defects and the 70% of them don’t have a known cause. Examples of genetic defects include spina bifida, cystic fibrosis and Down syndrome. Cleft lip/ palate (a genetic defect that causes problems in speech, eating and language) and Down syndrome (a genetic defect that result in short limbs, almond shaped eyes, enlarged tongue, etc.) are the most common genetic defects in the United States. Genetic defects are continuing to affect babies and one day it is hoped that they could be tested and treated right when a woman gets pregnant to get a better feedback to worried parents.

6. Additional Facts • The cause of 60% of genetic defects are unknown • Some genetic defects aren’t visible which is why that ultrasounds cannot always be used • In the US, about 120,000 babies are born each year with genetic defects • When the babies are living their first year of life, genetic defects are the leading cause of death • Genetic defects can shorten the lives of babies

7. Main Problem: Why We Need to Scan For Genetic Defects Before Birth? It’s important to test for genetic defects before birth because sometimes we are able to cure the defect or even find out about the defect and find way some way to end the birth of the baby so the parents won’t have to face the agony of a sick child. There are many scans that can detect many kinds of genetic defects. Our idea is to make a device that could be stronger than an ultrasound and thoroughly search for the defect.

8. Screening Techniques There are a variety of 3 screening techniques to detect birth defects. The first one is ultrasound, which uses sound waves that can’t be heard by the human ear to detect genetic defects. It is a non-invasive way to detect big problems in growth development. The downside is that is that you cannot check for genetic defects because the ultrasound doesn’t zoom in unless we upgrade the ultrasound greatly. The second technique amniocentesis, which uses a large needle to collect 20 ML of amniotic fluid. It is an invasive once the fetus has been carried for 16 weeks and it takes 2-4 weeks to get the results. After deciding to use amniocentesis, you cannot consider to abort the birth though it can detect all abnormalities by mapping up chromosomes and gives a 0.5% of miscarriage. Miscarriage is the risk of damaging the fetus with the needle. An amniocentesis can also produce infection, leakage, and other complications such as preterm labor and delivery, respiratory distress, postural deformities, fetal trauma and alloimmunisation (rhesus disease). The final technique of testing is CVS. It is also invasive but it works 8-12 weeks of carrying the fetus. It can detect the same things as an amniocentesis but the risk of miscarriage is 1%. Not only there is a chance in miscarriage, but there is a chance of infection and amniotic fluid leak. The result of the leaking fluid causes olighydramnios which can end up as a baby having underdeveloped lungs (Hypoplastic lungs). If the baby develops hypoplastic lungs, the lungs don’t have a chance to mature, and the baby can die shortly after birth.

9. What we studied Our group studied X-DNA, Quantum Dots, the Circulatory System forming in a baby inside a mother’s body, DNA, Genetics, Viruses, about the baby’s surroundings in a mother’s body. X-DNA is wider than regular DNA by 20%! Can Quantum Dots make the genetic defect in a cell light up? Will injecting a virus into a mother’s bloodstream be successful one day?

10. Possible Solution #1: X-DNA X- DNA What is X-DNA? X-DNA is a form of DNA but, it is 20% wider. Since it is wider, it would be easier to check for genetic testing using X-DNA because the size difference is bigger. Pros X-DNA is bigger than regular DNA so it would be easier to use to find genetic defects within the DNA. Cons X-DNA is not found in every body so if we developed a test for testing through X-DNA, it wouldn’t apply to every single person. Will This Solve the Problem? Checking for genetic defects using X-DNA may or may not work. It has not been tried yet. If someone would try it, we would use a very high powered microscope and look too check for genes affected with genetic defects. The reason we are trying to find a cure is because babies die a lot due to genetic defects and causes tragedy in people’s lives.

11. Possible Solution #2: Microscopes Using microscopes to check for genetic defects How would we do this? To do this, we would have to develop very powerful microscopes and use them to zoom into DNA and check for genetic defects. Pros No risk of miscarrige. Would work from beginning of pregnancy, as soon as fetus developed DNA Cons System has not been developed yet Microscopes with such power have not been made yet Will this solve the problem? If microscopes with such high power were made, then we would be able to look at DNA using them and there would be no risk of miscarrige when testing for genetic defects. Just the little risk of miscarrige in the tests for genetic defect testing that are already developed, (amnio. = .5% and CVS = 1%) is enough to scare the parents so they do the genetic defect testing. So if we did use very powerful microscopes, genetic testing would work without the risk of miscarrige, also at an earlier time than CVS and amniocenthesis. This encourages most people to get themselves checked and make sure their kids will not inheret a genetic defect.

12. Possible solution #3: Non-Invasive Method To Test For Genetic Defects Invasive methods of testing fetuses for genetic defects could cause a small risk in miscarriage that could have some people change their minds about testing. Other methods can be used that are non-invasive and pose no risk of miscarriage at all, especially a blood test for the mother. In the first five weeks of the baby’s development, the placenta starts to lose and shed its cells, which contain the baby’s DNA, into the mother’s bloodstream. If we take the mother’s blood and search for those cell fragments, we can find the baby’s DNA and test that for any genetic defects without using the invasive methods. But these fragments cannot determine the final gene set of the baby, because the gene activity in various organs can slightly change without reflecting that change in the placenta’s DNA. So for this reason this method would not substitute the invasive and alternate methods, since it will not determine the baby’s resulting DNA set, compared to getting the original set from the baby’s own cells.

13. Final Solution For this method we will take a non pathogenic virus, which will target a specific cell, and insert it into the mother’s bloodstream. It will then pass through to the baby and into one of its cells.

14. Description of the Process This new method for testing for genetic defects in fetuses will be done by using a non-pathogenic and harmless Virus Vector, which will target a specific cell in the body of the fetus. This virus will contain polymerase to break apart the strands of DNA on the needed gene, artificial RNA that would render a translated protein useless, and possibly Ribozyme (an enzyme that can join two segments of RNA). To transport the virus to the fetus, it will be injected into the mother’s bloodstream where it will, in about 30 minutes, pass through the mother’s placenta unnoticed (because the virus will be a kind that can’t be detected by the immune system) and enter one of the cells in the fetus. Upon entrance the virus will completely break apart in the nucleus and release all of its components. The Polymerase will separate two strands of DNA of a specific gene, and with the use of one of the DNA strands and free nucleotides, it will build one complementary strand called RNA (which in comparison to DNA will have Uracil in its sequence instead of Thymine). Meanwhile the artificial RNA from the virus will attach to the newly finished RNA right before the stop codon, possibly with the help of the Ribozyme from the virus. This altered RNA will mature into messenger RNA, which will then transport itself outside the nucleus and to the nearest ribosome. This ribosome will translate the mRNA sequence and gather specific amino acids based on it, until it encounters the stop codon in the sequence. When the chain of amino acids is finished it will separate from the ribosome and fold itself into a protein. Since this protein was translated from the specifically altered RNA, it will be dysfunctional and be ejected from the cell and into the bloodstream. Afterwards it can be detected by simple blood tests and decoded back into the original RNA sequence (of course you would also have to exclude the decoded sequence of the attached artificial RNA). Lastly, the RNA can be analyzed and checked for any genetic defects, and you can finally know if the fetus has any genetic defects on a specific gene.

15. Virus(enlarged) Virus Enters Target Cell Cell Artificial RNA and polymerase Inside Nucleus Polymerase is released from virus, which breaks apart the DNA strands Free nucleotides Free nucleotides The DNA separates DNA of one gene of a targeted cell Virus breaks apart and releases polymerase and artificial RNA Free nucleotides pair up with one of the strands of separated DNA to make a complementary strand

16. Formerly separated DNA strands rejoin Artificial RNA from virus attaches itself to original RNA Complementary strand separates from DNA strand and is now RNA RNA forms Into mRNA Amino Acids That will form protein Newly formed RNA which matures into mRNA Ribosome Cell The ribosome translates the altered mRNA, and according to its code, it will collect and form a chain of amino acids based on it. Altered mRNA exits nucleus and goes to nearest ribosome Virus’s artificial mRNA Ribosome Ribosome

17. Protein (enlarged) Amino Acids are formed into protein. This protein will not serve any function in the cell, because of the encoded amino acids from the artificial mRNA. Without any function to serve, the protein is sent outside the cell. The protein will eventually travel from the baby into the umbilical cord, into the placenta, and finally into the mother’s blood where it can be tested, and decoded to see what the gene’s DNA was.

18. The Solution….Animated

19. When To Start the Process • Blood vessels start form in the placenta: Day 13 • Blood cells already formed, begin to develop channels: • Day 17 - 19 • Secondary blood cells come into view in the placenta: Day 19 – 21 • Blood vessels continue to shape: Day 23 – 30 • Blood flow is entirely purposeful: Week 16 • Blood vessels are beneath skin: Week 22 • Blood vessel comes further near skin: Week 24 • To inject a virus and check for genetic defects through that, we must wait for blood vessels and the placenta to form in the fetus. At least half of the blood vessels should be formed for safety of the baby, but is not necessary, so if even if some of the cells are taken from the fetus, the fetus won’t be harmed.

20. What We Learned From brainstorming world problems to squeezing information into a power point, we have learned a lot about cooperation, genetic defects, and about how we function. We all strived for perfection by working hard and we learned that not only does perseverance pays off, but also learned to trust our teammates and divide tasks. It was hard to put everything that we brainstormed into a power point but we managed based on taking turns adding slides and lots of time trying to make it as organized and as thorough as possible. We took lots of notes beforehand even though at first, we did not know where we were heading. We researched many unnecessary things, some though lead us into coming up with a solution for how genetic defects could be tested as early as possible. We had lots of ideas, but not a specific answer. Finally, Katya came up with a detailed solution and we learned so much about it. We learned to admire our comrades with whatever ideas they came up with. We learned to respect each others way of thinking. We understood that some can comprehend things faster than others and we found out that being patient helps. We helped each other out when they were stuck. We learned how to work our way up to the deadline when it was near. Everyone understood that our goal was not only to finish a project, but to lead scientists into a path, a path that could one day help families, parents and babies live a healthy, happy life. We know that how hard you must work to accomplish a goal and we thank TeXplore for that.

21. Who Are We? Who Are We? Who Are We? Who Are We? WHO ARE WE? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? WHO ARE WE? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We? Who Are We?

22. It’s a me, Jazib and I’m 11 years old. I like to play video games and read books by Darren Shan Like Cirque Du Freak series, Lord Loss series and other books and I like to sleep………… a lot. I’m a computer whiz who does a lot with the programs and making my own things. My cousin Anosh is also doing Tech X-Plore with me and we are such good friends (SHE ROCKS)! I play a lot of Speed-a–Way, soccer, badminton, tennis, and basketball. I really want to be a doctor when I grow up and my favorite school subjects are science, math, and gym. I love the color green and I love Donkey Kong, Mario, Legend of Zelda, and other Nintendo Wii games. I study a lot and I get very pleased when I get As and A+s. I LOVE to watch cartoons all day in pajamas on free days. I Love to watch Looney Toons, Tom and Jerry, Family Guy, and the Simpsons, (HOMER IS MY IDOL!). I like to play play guitar and piano, I take piano, guitar, voice, Hip-Hop, Ballroom lessons and I go to John Robert Powers acting and modeling school. I had a photo shoot for a Scott Foresman Pearson textbook for reading in a 2010 edition. So basically, I am a fun guy who does many, many things. I also love to see penguins waddle left to right and move their cute little tushes (GO PENGUIN TUSHIES)!I LOVE PENGUINS, KOALAS, KANGAROOS,KUMQUATS, AND FURRY ANIMALS! I LOVE THE SCENTS AND TASTES OF PUMPKIN, PUMPKIN SPICE, AND SEAWEED!! THE BEST MOVEMENT I’VE EVER SEEN IS WADDLING PENGUIN TUSHIES!! Jazib

23. Anosh My name is Anosh. I am 11 years old and a 6th grader at Old Orchard Jr. High. I have a cousin doing TechXplore as well. His name is Jazib. He came to America when he was only 9 months old. Jazib is in the acting business. I came to America from Pakistan at age 5. I have a little brother, age 10. He is in the 4th grade. In my free time I like to read and play sports. My favorite series is The Cirque Du Freak and I am in the middle of it right now. I like to read suspenseful or scary books. I learned to read and write at age 3. My dad is a high school math teacher and my mom is a doctor. My favorite color is red. That’s pretty much it. This is all about me!

24. Iris My name is Iris. This is my first year doing TechXplore and I really enjoy researching on my topic. Outside of school I like to read, watch T.V and spend time with my family. I take swimming, dancing, Spanish and voice lessons. I’m not sure what I want to be when I grow up but teaching sounds fun and I’m very interested in the human body and other medical-like things. My favorite food is spaghetti and my favorite desert is ice-cream. If I got to travel to one place in the world for free, I’d go to New Zealand because there are a lot of different types of penguins there and I’d like to come face to face with a penguin. My favorite subject is writing because I find it very exciting. My favorite types of essays are persuasive essays because I love arguing for something I believe in. For these types of essays, I could write two or three pages or more because it’s fun! I really liked reading the Harry Potter series and can’t wait for the last movies! One of my favorite books is Stargirl because I liked the lesson, that’s it’s O.K. to be yourself.

25. Katya My name is Katya Gribkova, and I live in Skokie Illinois, even though I was originally born in Moscow, Russia on January 13, 1994. I like to play tennis, piano, and study science and mathematics. I go to Old Orchard Junior High School as an eighth grader, where I also participate in Science Olympiad. Sometimes I enjoy writing narrative essays and just writing poems in my spare time. My favorite sports in the summer are playing tennis, soccer, and swimming. In the winter, I go skiing on snowy hills in Kenosha, Wisconsin. I have enjoyed this wonderful school year so far, and it has been a pleasure being in TechXplore.

26. Our Advisors Mrs. Gaffney Mr. Lakdawala Mr. Lakdawala is our mentor for TechXplore He is an electrical engineer working for Hewlett-Packard (HP) for almost13 years. He has 20 years of experience as Hardware design engineerdesigning laptop computers. Mrs. Gaffney is the teacher at our group’s school who is in charge of the gifted program. She is our teacher advisor.

27. Conversations With Mr. Lakdawala We have some questions for you:1)Can we use nanotechnology to go and take amniotic fluid without therisk of miscarriage?2)We know that if the baby's parents are both carriers, the baby has a25% chance to inherit the disease, but what if both parents or only oneparent had a genetic defect. What would be the percentage of the baby'schance for the genetic defect the parent(s) had?3)How many genetic defects so far can be tested and cured before thebaby's birth?4)Could we test the umbilical cord for a genetic defect instead oftaking a sample of amniotic fluid from the amniotic sac?5)What do you do for a living and how long have you been doing you job?6)Are there any alternate ways instead of sampling amniotic fluid totest for genetic defects?Thank you so much for your time and for being our mentor.Sincerely,Anosh, Katya, Iris, and Jazib • Sent: Friday, October 19, 2007 2:04 PM • Hello, we are students from Old Orchard Jr. High School and are part ofthe TechXplore project. We wanted to introduce ourselves:Anosh likes to play soccer and read.Jazib likes to play video games, play guitar, and sleep.Iris likes to swim and to dance.Katya likes to play tennis and she is in Science Olympiad.Mrs. Gaffney is the Gifted Ed teacher here who is serving as our coach.We are all 6th graders, and Katya is an 8th grader.We are so excited to do Tech Xplore this year. We are trying to findmore and cheaper ways to test for genetic defects before a baby is born.We are also trying to find out how to take amniotic fluid and/orplacenta to test for genetic defects without the risk of miscarriage. Weknow that if someone is over 35 the risk of the person's child having agenetic defect increases and if they have a history of genetic defectsin their family, the risk of the baby being born with the genetic defectgoes up also.  We saw that Down Syndrome popped up a lot as weresearched the subject of genetic defects. Iris found out that DownSyndrome is caused by not enough, more than needed or damagedchromosomes. We also know that if someone abuses alcohol duringpregnancy, the risk of the baby being born with a genetic defect goesup.

28. Sent: Tuesday, October 23, 2007 1:55 PM Hello Everyone,Thank you for contacting me for the project. I am happy to know all ofyou and excited about being a part of TechXplore project.At the moment, I don't have answers to all your questions however I willtry to help address each as quickly as I could.I can answer your one question below:5)What do you do for a living and how long have you been doing you job?I am an electrical engineer working for Hewlett-Packard (HP) for almost13 years. I have 20 years of experience as Hardware design engineerdesigning laptop computers.Genetic is new topic for me so I will need to research before I can helpyou with all the questions.These are very good questions!I like to know following:1) Do you have any timeline or project guideline defined for thisproject?2) Do you have focus statement for the project?3) Have you put any material on TechXplore website that I can getfamiliarizes with?Please reply back with the answers to my question and any additionalquestions you may have.Thank you!Rahul Lakdawala ii) There are many different genetic defects that can be detected beforebirth, but very few can be cured.  One condition, Rh incompatibility canbe treated through Rh-immune globulin injections.Some of the questions that  parents need to ask themselves with geneticresults are:-How accurate are the test results? (is it possible there is a mistake?)-Can the baby survive this condition?  How long will he live?-What problems might be caused by the condition?-What is involved in caring for the child with this condition? etc4)Could we test the umbilical cord for a genetic defect instead oftaking a sample of amniotic fluid from the amniotic sac?i) Yes, there are cells from the child in the umbilical cord (like stemcells).  But I think it is much more difficult to remove cells from theumbilical cord then amniotic fluid.ii) Percutaneous umbilical blood sampling is used when rapid chromosomeanalysis is needed, particularly toward the end of pregnancy whenultrasonography has detected abnormalities in the fetus. Often, resultscan be available within 48 hours.There are greater risks to mother & fetus than testing amniotic fluid.5)What do you do for a living and how long have you been doing you job?6)Are there any alternate ways instead of sampling amniotic fluid totest for genetic defects?i) For inheritable diseases, yes.  The genetic make-up of each parentcan be determined and the risk of the child having the disorder can beobtained (I think a lot of couples do this to test for tourettessyndrome).  Or after the child has been born, there can be genetictesting to determine if there are any genetic defects.ii) Another common method takes a biopsy of the placenta (called CVS).The risks were thought to be higher in the past, but are proving to beequivalent to sampling amniotic fluid.Thank you!Rahul Lakdawala i) We can probably test for any genetic disorder that scientist know thecause of, for example which gene is defective in CF or which chromosomeis extra in down syndrome patients, then they can test for it.  But inorder to test for these diseases they must have cells from the baby,which is usually taken from the amniotic fluid or umbilical cord.Genetic disorders are not curable.  Genetic disorders are caused by adefect in every single cell in your body, it is at the genetic level.There has been some research attempts trying to use gene therapy to"cure" genetic disorders, but there are many challenges that researchersare trying to overcome.  One area of intense research is with diabetespatients (One type - I believe type II - is a genetic disorder).  Yetthere is still no current therapy on the market.  There are medicinesout there to help reduce the symptoms or side effects of some geneticdisorders.

29. Sent: Saturday, November 10, 2007 3:15 PM Hi Anosh,Thanks for responding to my email.I am still checking on one more thing on your question but so far this is what I have.Laser is used for destroying cell and can't be applicable to zoom in to view the cells.Microscopic technology can be used to view chromosome is possible but I don't believe at the level of genes. I am confirming that but at this point this is what I think.Let me know if this helps answer your question or not.How is project going?Are you on track?How can I find out more about the project status and what the team has developed so far?Please let me know....Thank you!Rahul Lakdawala Sent: Friday, November 09, 2007 12:55 PM Hi, I am Anosh replying for my team. One question my team had for youis: Do you know if laser or microscope techonology can zoom into celllevel so we can look at genes and check for genetic defects that way?Thank you so much for your answers so far.Sincerely, Anosh

30. Hi Everyone,I tried looking for different microscope technology however I didn't find anything that can meet this application.Please let me know your response to the questions I asked in last email. Thanks and let me know if I could be of any assistant.Happy Thanksgiving to all!Thank you!Rahul Lakdawala

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32. Closing As you can see, genetic defects are big problems that need to be detected as soon as possible. This is why, with our solution, we can detect genetic defects earlier than other tests and make parents happy also. We hope our idea can influence people to research thoroughly about genetic defects, how they can be treated and more.