1. Implications of Tay-Sachs Disease: A Case Study for Public Knowledge By: Adam Green Wake Forest University Department of Biology

2. What am I doing? My goals are to explain: What is Tay-Sachs Disease? 3. What am I doing? My goals are to explain: What is Tay-Sachs Disease How is it determined? 4. What I am doing? My goals are to explain: What is Tay-Sachs Disease How is it determined? Who can have it and how lethal is it? 5. What am I doing? My goals are to explain: What is Tay-Sachs Disease How is it determined? Who can have it and how lethal is it? What are the treatment options? 6. What am I doing? My goals are to explain: What is Tay-Sachs Disease How is it determined? Who can have it and how lethal is it? What are the treatment options? How can it be prevented? 7. Patient Case Study and Ethics Afterwards, I will present a mock patient case study and an ethical dilemma. 8. Interactive Quiz Bowl At the end of each section, there will be quiz questions. 9. Interactive Quiz Bowl You will work in teams and you will have two minutes to answer each question. 10. Note of Warning Before Beginning: You should have a competent understanding of DNA, RNA, and the Central Dogma 11. Note of Warning Before Beginning: You should have a competent understanding of DNA, RNA, and the Central Dogma Genes and the types of mutations 12. Notes of Warning Before Beginning: You should have a competent understanding of DNA, RNA, and the Central Dogma Genes and the types of mutations The endomembrane system 13. Note of warning Before Beginning: You should have a competent understanding of DNA, RNA, and the Central Dogma Genes and the types of mutations The endomembrane system The Plasma Membrane 14. Notes of Warning Before Beginning: You should have a competent understanding of DNA, RNA, and the Central Dogma Genes and the types of mutations The endomembrane system Plasma Membrane Here are some helpful links: http://www.ncbi.nlm.nih.gov/Class/MLACourse/Modules/ MolBioReview/slide_list.html http://www.youtube.com/watch?v=UAaTEjYmxso http://en.wikipedia.org/wiki/Cell_membrane 15. Lets Begin! Please spilt into teams 16. What is TaySachs Disease It is a lysosomal storage disorder due to genetic mutations in the HEX A gene. 17. What is TaySachs Disease? One common mutation is a 4 base insertion in the HEX A gene. 18. What is TaySachs? As we know, this could change how the RNA is transcribed and the resultant protein. 19. What is TaySachs Disease? And in fact, it does change the protein. The HEX A gene is responsible for the production of an enzyme(protein) called hexsaminidase A that is responsible for breaking down fatty substances called GM2 gangliosides that can accumulate in our brains and spinal cords. 20. What is TaySachs Disease? These enzymes(proteins) are made on ribosomes attached to the rough ER and sent to lysosomes that act as recycling centers to break down toxic substances such as fatty substances called GM2Gangliosidies that accumulate in our nervous system. Often lack of function of these enzymes results in death. 21. What is TaySachs Disease? GM2 gangliosides contain a long hydrophobic tail that inserts itself into the plasma membrane of ganglion cells in neurons surrounding the retina of our eyes.Pictures: (top) Hexsaminidase with both alpha and beta subunits. Only the alpha subunit is involved in Tay-Sachs Disease. (bottom) is a depiction of a GM2-ganglioside. 22. What is TaySachs Disease? They also contain acidic groups called head groups that stick above the plasma membrane and can be involved in cell-cell recognition as a result. While the exact function of GM2 Gangliosides is unknown, it has been suspected that they serve as an intermediate in the synthesis of more complex gangliosides needed for normal brain development. 23. What is TaySachs Disease? This would explain why the enzyme HEX A cleaves part of the ganglioside and the absence of this enzyme results in improper brain development often culminating in death. 24. What is TaySachs Disease? On another note, this disease is known as an autosomal recessive disorder 25. What is TaySachs Disease? An autosomal recessive disorder means that the mutation in the HEXA gene exists in two alleles. Alleles are alternative form of a gene. Humans contain two sets of genes, one from their mother, and one from their father. The offspring must have two alleles, one from the mother and the father, in order for the disease to be expressed. 26. What is TaySachs Disease? The actual enzyme activity required by -hexosaminidase is very small in order to sufficiently break down GM2gangliosides. Thus, some individuals may only have one mutant copy of the HEXA gene. These individuals will have abnormally low enzyme activity levels, but still enough to break down fatty substances in your nervous system. They are called heterozygous carriers. 27. What is TaySachs Disease? If two of these heterozygous carriers with abnormal enzyme levels mate, they have a 25% chance of having a child affected with Tay-Sachs Disease. This would mean that each parent has 1 mutant copy out of two (1/2) and the child has both copies; thus the probability is x = or 25% that the child will be affected. This is the basis for a recessive disorder. We see in this family tree, the offspring ratio is 3:1 and 25% chance of being affected. 28. What is TaySachs Disease We can also illustrate this concept through a punnett square. Lets represent A as the normal HEX A allele(alternative form of gene) and a as the mutant allele that produces abnormal HEX A enzyme levels. 29. What is TaySachs Disease? As you can see, when you cross two heterozygotes, you get a 25% chance of being affected. 30. What is TaySachs Disease? Now, to further complicate matters, it is important to realize that more than 120 mutations have been found in the HEX A gene. These mutations vary in the amount of -hexosaminidase they produce and thus lead to less severe forms of the disease. 31. What is TaySachs Disease This leads to two subtypes of Tay- Sachs Disease: 1) Early-onset Infantile: the child possesses two mutant copies of the HEX A and produces no functional enzyme. This the most severe. 32. What is TaySachs Disease? This leads to two subtypes TaySachs Disease: 1) Early-onset Infantile: the child possesses two mutant copies of the HEX A and produces none of the functional enzyme. This the most severe. 2) Late onset adult: disease caused at times by compound heterozygosity that I will explain later. Patient has abnormal enzyme levels resulting in late-onset disease.The images present a young child with Tay-Sachs and an adult with Tay-Sachs 33. Time for Quiz Questions!! Ready your teams! 34. Quiz Question 1 The following Base Sequence is the normal gene sequence: AGTCGTTAACCAG Although the above sequence is not the HEX A gene, what mutational sequence below could be analogous to Tay-Sachs? A. AGTCGTTCAACCAG B. AGTCGTTCCAACCAG C. AGTCGTTCCGGAACCAG D. : AGTCGTTAACCAG 35. Quiz Question 1 Times up! Report your answers 36. Quiz Question 1 The following Base Sequence is the normal gene sequence: AGTCGTTAACCAG Although the above sequence is not the HEX A gene, what mutational sequence below could be analogous to TaySachs? A. AGTCGTTCAACCAG B. AGTCGTTCCAACCAG C. AGTCGTTCCGGAACCAG D. : AGTCGTTAACCAG THE ANSWER is C. A common mutation found in the HEX A gene can result from a 4 base pair insertion! Give yourself 2 points if you got it right. But note, that other mutations are also possible. 37. Quiz Question 2 Brace yourselves! 38. Quiz Question 2 If a male contains one mutant allele for the HEX A gene (Aa) and the female contains two normal alleles(AA), then what is the chance that they will have an offspring with Tay-Sachs? Hint: Draw a Punnett Square. A. 75% B. 60% C. 25% D. None of the above 39. Quiz Question 2 Times up! Report your Answers! 40. Quiz Question 2 If a male contains one mutant allele for the HEX A gene (Aa) and the female contains two normal alleles(AA), then what is the chance that they will have an offspring with Tay-Sachs? Hint: Draw a Punnett Square. A. 75% B. 60% C. 25% D. None of the above THE ANSWER IS D. Tay-Sachs is a recessive disorder meaning that the offspring has to have two mutant alleles. Only one mutant allele is available. The answer should be 0%. 41. Question 2: mathematics explained Here is an example of how this problem could be solved. 1) Make a punnett square.A AAAAAa AAaAa2)Perform data analysis. For example, we can say that 2/4 of the offspring or 50% will be heterozygous carriers. The remaining 50% will be homozygous dominant; thus, since there are no homozygous recessive offspring, we can say there is a 0% probability of the offspring having a recessive disease such as Tay- Sachs. 42. Quiz Question 3 Brace yourselves! 43. Question 3 The following blood test was conducted on a patient. The lab found his -hexosaminidase levels to be operating at 15%. This means that 15% of the enzymes were functioning normally. Can we conclude the patient has Tay-Sachs? A. Yes B. No C. Not sure yet. 44. Question 3 Time is up! Report your answers 45. Question 3 The following blood test was conducted on a patient. The lab found his -hexosaminidase levels to be operating at 15%. This means that 15% of the enzymes were functioning normally. Can we conclude the patient has Tay-Sachs? A. Yes B. No C. Not sure yet. THE ANSWER IS B. Remember that the enzyme only requires small amounts to function normally. This also ties in to our discussion about different mutations producing different activity levels. We will discuss more about critical thresholds in the next section. 46. Tally your scores Tally your points. The maximum score is 6 and the minimum score is 0. 47. How is TaySachs Disease determined? Now that we know what this disease is. We need to know how is it determined in the lab. 48. How is TaySachs Determined? Tay-Sachs is primarily determined by a blood test. An individual with a family history of Tay-Sachs can consult their physician and receive a simple blood test that measures hexosaminidase levels. 49. How is TaySachs Disease Determined? Remember Quiz Question 3? Well, it turns out that individuals affected with TaySachs Disease have between 0% activity to 10% activity. Infantile Tay-Sachs patients have 0%. Adult patients have an activity level between 510% to produce symptoms. Any amount greater than 10% will result in no symptoms. 50. How is TaySachs Determined? Individuals with blood levels at or below this critical threshold possess visible symptoms such as: 51. How is TaySachs Disease Determined? Individuals with blood levels at or below this critical threshold possess visible symptoms such as: 1) Cherry red- spot: results from the accumulation of GM2gangliosides that can block blood supply, disrupt a patients vision, and inhibit normal brain development. Prime indicator of Tay-Sachs. 52. How is TaySachs Disease Determined? Individuals with blood levels at or below this critical threshold possess visible symptoms such as: 1) Cherry red- spot: results from the accumulation of GM2gangliosides that can block blood supply and disrupt a patients vision. Prime indicator of Tay-Sachs. 2) In children, symptoms arise within 3 to 6 months. Children lose motor skills such as the ability to crawl. 53. How is TaySachs Disease Determined? Individuals with blood levels at or below this critical threshold possess visible symptoms such as: 1) Cherry red- spot: results from the accumulation of GM2gangliosides lipids that can block blood supply and disrupt a patients vision. Prime indicator of Tay-Sachs. 2) In children, symptoms arise within 3 to six months. Children lose motor skills such as the ability to crawl. 3) Eventually, affected individuals can experience seizures, paralysis, and loss of intellectual abilities due to their nerve cells dying. 54. How is TaySachs Disease Determined? Individuals with blood levels at or below this critical threshold possess visible symptoms such as: 1) Cherry red- spot: results from the accumulation of GM2gangliosides lipids that can block blood supply and disrupt a patients vision. Prime indicator of Tay-Sachs. 2) In children, symptoms arise within 3 to six months. Children lose motor skills such as the ability to crawl. 3) Eventually, affected individuals can experience seizures, paralysis, and loss of intellectual abilities due to their nerve cells dying. 4) Microscopic Analysis can also find the retinal neurons to be bloated from excess ganglioside storage.Pictures: The top image represents bloated retinal neurons from excess ganglioside storage due to hexosaminidase deficiency. 55. How is TaySachs Determined? My next concern is how can a mutation or mutations in the Hex A gene be determined? 56. How is TaySachs Determined? The answer can be solved through three related methodologies: 1) PCR 57. How is TaySachs Disease Determined? The Answer can be solved through three related methodologies: 1) PCR 2) Gel Electrophoresis 58. How is TaySachs Disease Determined? The Answer can be solved through three related methodologies: 1) PCR 2) Gel Electrophoresis 3) DNA Sequencing 59. How is TaySachs Disease Determined? PCR stands for polymerase chain reaction. This is done to amplify a specific segment of a chromosome such as the HEX A gene or even a specific segment of the Hex A gene. The process can occur in 4 easy steps: 60. How is TaySachs Disease Determined? PCR stands for polymerase chain reaction. This is done to amplify a specific segment of a chromosome such as the HEX A gene or even a specific segment of the Hex A gene. The process can occur in 4 easy steps: 1) RNA isolation: You have to isolate the RNA from your sample and covert it back to DNA using enzymes known as reverse transcriptases. This allows you to only amplify the region that is expressed. 61. How is TaySachs Determined? PCR stands for polymerase chain reaction. This is done to amplify a specific segment of a chromosome such as the HEX A gene or even a specific segment of the Hex A gene. The process can occur in 4 easy steps: 1) RNA isolation: You have to isolate the RNA from your sample and covert it back to DNA using enzymes known as reverse transcriptases. This allows you to only amplify the region that is expressed. 2) You then apply heat to your DNA to pull the strands apart. 62. How is TaySachs Determined? PCR stands for polymerase chain reaction. This is done to amplify a specific segment of a chromosome such as the HEX A gene or even a specific segment of the Hex A gene. The process can occur in 4 easy steps: 3) Anneal primers: attach thermostable DNA sequences to your DNA to begin the process of amplification 63. How is TaySachs Determined? PCR stands for polymerase chain reaction. This is done to amplify a specific segment of a chromosome such as the HEX A gene or even a specific segment of the Hex A gene. The process can occur in 4 easy steps: 3) Anneal primers: attach thermostable base DNA sequence to your DNA to begin the process of amplification 4) Add a thermostable polymerase to attach to your primers and begin replication. 64. How is TaySachs Determined? PCR stands for polymerase chain reaction. This is done to amplify a specific segment of a chromosome such as the HEX A gene or even a specific segment of the Hex A gene. The process can occur in 4 easy steps: 3) Anneal primers: attach thermostable base DNA sequence to your DNA to begin the process of amplification 4) Add a thermostable polymerase to attach to your primers and begin replication 5) Repeat to desired amplification. Picture: Diagram explaining PCR. 65. How is TaySachs Determined? Now that you amplified DNA, you can place it on a gel and run an electric field through your DNA segment. The amplified DNA will show up on the gel and move along the gel against the negative electrode since DNA contains negatively charged phosphate groups. 66. How is TaySachs Determined? Mutant Hex A can be the result of a 4 base pair insertion; thus, it would have more phosphate groups and move less along the gel than a normal HEX A DNA due to larger molecules getting stuck in the gel. Think of the gel as a sieve.The following picture is an example of data from a gel electrophoresis experiment. Smaller DNA fragments move farther than larger DNA fragments. 67. How is TaySachs Determined? Since Tay-Sachs is caused by mutations, you can sequence the HEX A gene of a normal individual and an affected individual and see the DNA change. This is done in two ways: Sanger Sequencing and Cycle Sequencing via primers. Attached are two videos to watch that explains it in more detail:1) http://www.dnalc.org/resour ces/animations/sangerseq.ht ml 2) http://www.dnalc.org/view/1 5923-Cycle-sequencing.html Picture on right depicts Fred Sanger who developed Sanger Sequencing. He recently died at the age of 95. 68. QUIZ TIME!! Now that you understand how mutations in the HEX A gene can be determined, you can answer these questions! Ready your troops! 69. Quiz Question 4: A mother reports to her physician that her 4 month year old just sits in one place for hours with no movement. She has to be the one to move him at all times. She suspects he may be paralyzed. What should the doctor suggest first in his/her diagnosis? A. Look for observational clues such as a cherry red spot B. Perform a Microscopy Analysis to search for distended neurons C. Order a blood test to look for decreased hexosaminidase activity levels. D. Nothing. The woman is just a paranoid new mother. 70. Question 4 Times up!! Report your Answers!! 71. Question 4 A mother reports to her physician that her 4 month year old just sits in one place for hours with no movement. She has to be the one to move him at all times. She suspects he may be paralyzed. What should the doctor suggest first in his diagnosis? A. Look for observational clues such as a cherry red spot B. Perform a Microscopy Analysis to search for distended neurons C. Order a blood test to look for decreased -hexosaminidase activity levels. D. Nothing. The woman is just a paranoid new mother. THE ANSWER IS A. While B and C are also possible, A is a prime indicator of Tay-Sachs and is the easiest and probably most convenient way to confirm Tay-Sachs. 72. Quiz Question 5 Brace yourselves!! 73. Question 5 What feature of DNA structure dictates our rationale that HEX A mutants with base pair insertions will result in shorter distances along a gel? A. Phosphate groups. B. Sugar groups C. Base pairs. D. acridine ligands 74. Question 5 Times up! Report your Answers! 75. Question 5 What feature of DNA structure dictates our rationale that HEX A mutants with base pair insertions will have shorter distances along a gel? A. Phosphate groups. B. Sugar groups C. Base pairs. D. acridine ligands THE ANSWER IS A. While The phosphates in the DNA backbone contain a negatively charged oxygen that cause the DNA to repel against the negative charged electrode, larger DNA fragments get stuck in the gel more than smaller fragments and thus move less. 76. Tally your scores! The most points awarded up to this point are 10 points(2 points per question). The least points awarded are 0 points 77. How lethal is this disease? Now that we understand what Tay-Sachs disease is and how it can be determined, we still need to understand one other factor before we can do a patient case study. This last factor is lethality. 78. How lethal is this disease? The most common form of TaySachs disease is infantile TaySachs. Symptoms normally appear around 3 to 6 months. The maximum longevity is sadly only about 4 years or simply a brief extent into early childhood. 79. How lethal is this disease? Adult onset disease is more variable depending on the mutation and actual amount of -hexosaminidase activity present in the cell. 80. How lethal is this disease? Another factor for adult onset Tay-Sachs disease is the issue of compound heterozygosity that I mentioned previously. 81. How lethal is this disease? Compound Heterozygosity is just weird. It occurs when an individual has two recessive allele mutations in the HEX A gene at different locations in the genome. This is indicative of the fact that there are over 120 mutations found in the HEX A gene. This can contribute to adult onset Tay-Sachs as a result. 82. How lethal is this disease? Another aspect of lethality is the prevalence. According to recent studies, 1 out of every 300 people in the population is a heterozygous carrier for Tay-Sachs disease. However, for individuals who belong to a certain ethnic group known as the Ashkenazi Jews, the prevalence increases from 1 in 300 people to 1 in 30 people who will be a heterozygous carrier.Picture on the right depicts women of Ashkenazi Jewish heritage. They are genetically European. 83. How lethal is this disease? The reason why the ratio is so much greater for Ashkenazi Jews is likely due to geographic distributions. A paper published in the American Journal of Human Genetics found the frequency of the HEX A mutation to be greater in geographically isolated regions with the highest frequencies in countries such as Russia, Lithuania, and other central and eastern European countries where the Ashkenazi Jews originated. As a result, the ratio is likely just bad luck.Figure. The geographic locations of the Ashkenazi Jews located in western and eastern Europe including Russia.Russia 84. Quiz Time!! Brace yourselves!! 85. Quiz Question 6 Which of the following pieces of evidence favors random bad luck for the HEX A mutation in the Ashkenazi Jewish population? A. The ratio for a carrier is 1 out of 30 instead of 1 out of 300. B. High mutation frequency in one location and no frequnecy in other locations. C. Heterozygous carriers are capable of producing subnormal enzyme activity levels to prevent symptoms from appearing. D. Some mutations in the HEX A are more deadly than others. 86. Quiz Question 6 Times up!!! Report your Answers! 87. Quiz Question 6 Which of the following pieces of evidence favor random founder effects over heterozygous advantage for the HEX A mutation in the Ashkenazi Jewish population? A. The ratio for a carrier is 1 out of 30 instead of 1 out of 300. B. High mutation frequency in one location and no frequency in other locations. C. Heterozygous carriers are capable of producing subnormal enzyme activity levels to prevent symptoms from appearing. D. Some mutations in the HEX A are more deadly than others. THE ANSWER IS B. Random founder effects occur from genetic breeding/sampling in isolated populations over long timespans. 88. Case Study of Alex Now that you understand the basis of Tay-Sachs Disease We can examine a mock case study. Lets begin 89. Meet Alex Alex, short for Alexander, is from Russia with two Russian parents. They are part of the Ashkenazi Jewish heritage. 90. Meet Alex Alex, short for Alexander, is from Russia with two Russian parents. They are part of the Ashkenazi Jewish heritage. He is 3 months old. 91. Meet Alex Alex, short for Alexander, is from Russia with two Russian parents. They are part of the Ashkenazi Jewish heritage. He is 3 months old. Alex is the first child of his parents. 92. Meet Alex Alex, short for Alexander, is from Russia with two Russian parents. They are part of the Ashkenazi Jewish heritage. Alex is 3 months old. Alex is the first child of his parents A physician observed an eye abnormality called a cherry red spot through a simple eye examination. 93. Quiz Question 7 Brace yourselves! 94. Quiz Question 7 What should the doctor order based on these evaluations? A. blood test to measure -hexosaminidase levels. B. motor skills test. C. Microscopy analysis of bloated nerve cells. D. blood test to measure - hexosaminidase levels. 95. Quiz Question 7 Times up! Report your Answers! 96. Quiz Question 7 What should the doctor order based on these evaluations? A. blood test to measure -hexosaminidase levels. B. motor skills test. C. Microscopy analysis of bloated nerve cells. D. blood test to measure - hexosaminidase levels. THE BEST ANSWER IS D. Currently, the evidence is strong for Tay-Sachs Disease, but we need to see if the enzyme activity levels are below the critical threshold levels. 97. Tally your scores! The maximum points possible are now 14 points. 98. Alex The Blood test results are in and the enzyme activity levels are immeasurable which indicates infantile TaySachs Disease. 99. Quiz Question 8 Brace yourselves! 100. Quiz Question 8 What should the doctors next recommendation be? A. Order the lab to characterize the mutation through PCR and gel electrophoresis B. Nothing. The blood test is enough evidence.C. Contact a genetic counselor D. Re-run the blood test to confirm accuracy. 101. Quiz Question 8 Times up! Report your answers 102. Quiz Question 8 What should the doctors next recommendation be? A. Order the lab to characterize the mutation through PCR and gel electrophoresis B. Nothing. The blood test is enough evidence. C. Contact a genetic counselor D. Re-run the blood test to confirm accuracy. THE ANSWER IS A. While one blood test is good evidence, it does not tell us anything about the genetics of the individual. Thus, it does not inform us if a mutation is actually present. 103. Quiz Question 9 The results are in: 104. Quiz Question 9 The results are in: PCR and gel electrophoresis confirm shorter PCR products indicating a base insertion. 105. Quiz Question 9 The results are in: PCR and gel electrophoresis confirm shorter PCR products indicating a base insertion. DNA Sequencing confirms a 4 base addition for the HEX A gene. 106. Quiz Question 8 The results are in: PCR and gel electrophoresis confirm shorter PCR products indicating a base insertion. DNA Sequencing confirms a 4 base addition for the HEX A gene. This agrees with the blood test and observational clues to confirm Tay-Sachs Disease. 107. Quiz Question 9 Now Brace yourselves! 108. Quiz Question 9 What are the possible treatment options given this new diagnosis? A. Gene therapy approaches that engineer viruses which will turn the nerve cells into micro factories that produce -hexosaminidase. B. Developing synthetic chaperones that guide the hexosaminidase to fold into its native 3D structure.C. Replace the -hexsaminidase enzyme just like diabetics undergo insulin replacement. D. Use alternative enzymes that catabolize GM2gangliosides 109. Quiz Question 9 Times up Report your answers! 110. Quiz Question 9 Patient X= The correct answer is none of the above. All of the answer choices exhibit examples of positive research results, but they are all still a long away from actual clinical treatment. So for now, Tay-Sachs disease, in particular the more common Infantile TaySachs Disease is a genetic death sentence that will shut down a childs nervous system before he/she reaches kindergarden. 111. Quiz Question 9 As a result, when it comes to Tay-Sachs Disease, especially infantile Tay-Sachs, no one is a winner and thats why no points are awarded for this question. 112. Quiz Question 9 As a result, when it comes to Tay-Sachs Disease, especially infantile Tay-Sachs, no one is a winner and thats why no points are awarded for this question. Since Alex is afflicted with this disease, he will die and his parents will be left childless. 113. Can this disease be prevented or minimized? 1) Pre-natal genetic diagnosis: The parents can be tested to see if they are carriers and if their offspring is carrying both recessive alleles within 10 to 14 weeks. The parents could then opt for abortion. 114. Can this disease be prevented or minimized? 1) Pre-natal genetic diagnosis: The parents can be tested to see if they are carrier and if their offspring is carrying both recessive alleles within 10 to 14 weeks. The parents could then opt for abortion. 2) Pre-implantation diagnosis: during in vitro fertilization, you simply discard embryos that test positive for Tay-Sachs disease. 115. Can this disease be prevented or minimized? 1) Pre-natal genetic diagnosis: The parents can be tested to see if they are carrier and if their offspring is carrying both recessive alleles within 10 to 14 weeks. The parents could then opt for abortion. 2) Pre-implantation diagnosis: during in vitro fertilization, you simply discard embryos that test positive for Tay-Sachs disease. 3) 3) Mate Selection: Some Orthodox Jewish groups such as Dor Yeshorim perform a genetic screening program that allows couple who test positive as carriers can avoid conception. 116. Can this disease be prevented or minimized? These three strategies are pretty drastic and indicate that we may still be a while away from actual treatment options for this rare deadly disease. As a result, these strategies have presented us with two ethical dilemmas. 117. Ethical Dilemma? Does the current situation make an appropriate case for abortion given that not all Tay-Sachs patients die in infancy or childhood? In this particular case, is knowledge good, bad, or ambivalent? 118. Ethical Dilemma? These are the important questions that we must address and I leave them for you to decide the answer. 119. Thanks for participating! 120. Assorted Links and Works Cited http://www.cdc.gov/mmwr/preview/mmwrhtml/000383 93.htm http://omim.org/entry/272800 http://link.springer.com/article/10.1007%2Fs00439003-1072-8 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1685578/ http://www.nature.com/mt/journal/v19/n6/full/mt20112 7a.html http://informahealthcare.com/doi/abs/10.1517/1354378 4.10.3.455 http://www.jbc.org/content/279/14/13478.long 121. Assorted Links and Works Cited http://www.ninds.nih.gov/disorders/taysachs/taysachs.h tm http://ghr.nlm.nih.gov/condition/tay-sachs-disease http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH000239 0/ http://www.genome.gov/10001220 http://commonhealth.wbur.org/2011/11/tay-sachshuman-trial http://newhoperesearch.org/GM2_gangliosidosis.html