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These are the user uploaded subtitles that are being translated: 0 00:00:00,000 --> 00:00:03,480 MICHAEL HEMANN: So what happens after a nondisjunction events? 1 00:00:03,480 --> 00:00:07,920 Well, in general aneuploidy meaning 2 00:00:07,920 --> 00:00:15,750 having a non-normal chromosome number is not tolerated. 3 00:00:15,750 --> 00:00:19,550 4 00:00:19,550 --> 00:00:32,659 So one in 800 live births has trisomy 21, 5 00:00:32,659 --> 00:00:33,740 which is Down syndrome. 6 00:00:33,740 --> 00:00:37,860 7 00:00:37,860 --> 00:00:40,470 And Down syndrome is really the only aneuploidy, 8 00:00:40,470 --> 00:00:42,210 is the only abnormal chromosome number 9 00:00:42,210 --> 00:00:46,620 for an autosome that is reasonably tolerated. 10 00:00:46,620 --> 00:00:55,020 So people with Down syndrome can grow and have a long life, 11 00:00:55,020 --> 00:00:58,470 but other trisomies are generally not tolerated. 12 00:00:58,470 --> 00:01:09,270 So trisomy 13 and 18 are viable, but they don't survive. 13 00:01:09,270 --> 00:01:13,010 So in general, these kids are not born. 14 00:01:13,010 --> 00:01:16,790 And if they are born, generally live less than a year. 15 00:01:16,790 --> 00:01:23,090 16 00:01:23,090 --> 00:01:32,440 Haploidy for autosomes is not tolerated. 17 00:01:32,440 --> 00:01:36,550 So nobody is born with only a single chromosome, 18 00:01:36,550 --> 00:01:38,530 a single autosome. 19 00:01:38,530 --> 00:01:40,450 These are all embryonic lethal. 20 00:01:40,450 --> 00:01:44,680 We actually in humans, we need two copies of every chromosome 21 00:01:44,680 --> 00:01:47,170 and rarely, rarely, rarely can tolerate 22 00:01:47,170 --> 00:01:48,910 three copies of a chromosome. 23 00:01:48,910 --> 00:01:51,280 There are a lot of interesting explanations 24 00:01:51,280 --> 00:01:57,280 in terms of dosage, appropriate gene dosage underlying 25 00:01:57,280 --> 00:02:01,040 the reason why this may occur. 26 00:02:01,040 --> 00:02:04,780 And there are also explanations why trisomy 21 may be viable. 27 00:02:04,780 --> 00:02:06,910 I mean, it's the smallest chromosome, so, perhaps-- 28 00:02:06,910 --> 00:02:10,240 or it may have the most minimal effect along 29 00:02:10,240 --> 00:02:13,630 with chromosome 22, but those are somewhat-- 30 00:02:13,630 --> 00:02:15,950 I think still somewhat speculative. 31 00:02:15,950 --> 00:02:21,700 So we do tolerate some changes in the numbers 32 00:02:21,700 --> 00:02:23,630 of X chromosomes. 33 00:02:23,630 --> 00:02:29,980 So you can survive as an XO, so an X chromosome and no Y 34 00:02:29,980 --> 00:02:31,600 chromosome. 35 00:02:31,600 --> 00:02:36,960 This is called Turner syndrome. 36 00:02:36,960 --> 00:02:39,420 You can be XYY. 37 00:02:39,420 --> 00:02:41,190 So you can have two Y chromosomes. 38 00:02:41,190 --> 00:02:43,260 People used to think that this actually 39 00:02:43,260 --> 00:02:47,220 led to a predisposition for committing crimes. 40 00:02:47,220 --> 00:02:50,010 I think that's been disproven to having too many Y chromosomes, 41 00:02:50,010 --> 00:02:53,260 but it was actually argued for a very long, long time 42 00:02:53,260 --> 00:02:55,575 that it makes people more violent. 43 00:02:55,575 --> 00:02:58,100 44 00:02:58,100 --> 00:03:04,670 XXY is Klinefelter syndrome. 45 00:03:04,670 --> 00:03:06,560 You can be XXXY. 46 00:03:06,560 --> 00:03:07,700 You can be XXXXY. 47 00:03:07,700 --> 00:03:13,340 48 00:03:13,340 --> 00:03:18,560 So you can tolerate increased numbers of the X chromosome. 49 00:03:18,560 --> 00:03:20,140 Many sense for why-- 50 00:03:20,140 --> 00:03:23,430 51 00:03:23,430 --> 00:03:25,710 yeah, there's a question what is the difference 52 00:03:25,710 --> 00:03:29,040 between viability and survival. 53 00:03:29,040 --> 00:03:37,110 Essentially I think they can be used interchangeable. 54 00:03:37,110 --> 00:03:41,670 In the case of trisomy 13 and 18, in this case, 55 00:03:41,670 --> 00:03:43,490 they can be born. 56 00:03:43,490 --> 00:03:48,560 So they can reach embryonic maturity. 57 00:03:48,560 --> 00:03:54,260 They can be born, and ostensibly most of the organ systems 58 00:03:54,260 --> 00:03:55,970 are appropriate, but many of them 59 00:03:55,970 --> 00:03:59,510 have serious, serious problems. 60 00:03:59,510 --> 00:04:02,720 And so these kids, again, really never 61 00:04:02,720 --> 00:04:05,070 survive to one year of age. 62 00:04:05,070 --> 00:04:08,400 So by survival here, I mean durable survival. 63 00:04:08,400 --> 00:04:15,590 So it's almost always associated with early lethality, which, 64 00:04:15,590 --> 00:04:19,220 of course, is a really difficult thing for parents. 65 00:04:19,220 --> 00:04:21,589 So there's a lot of embryonic testing 66 00:04:21,589 --> 00:04:25,970 to look for the status of trisomies, particularly 67 00:04:25,970 --> 00:04:29,810 these trisomy 13 and 18 that can lead 68 00:04:29,810 --> 00:04:34,310 to really devastating consequences for children. 69 00:04:34,310 --> 00:04:37,880 So why is it that you think we can tolerate larger 70 00:04:37,880 --> 00:04:40,190 numbers of X chromosomes? 71 00:04:40,190 --> 00:04:48,340 72 00:04:48,340 --> 00:04:53,960 Yeah, so it's because of this process of X chromosome-- 73 00:04:53,960 --> 00:04:59,020 well, there's-- yeah, you only express one X in general, 74 00:04:59,020 --> 00:04:59,520 right. 75 00:04:59,520 --> 00:05:02,820 So there's this process called Lyonization or X chromosome 76 00:05:02,820 --> 00:05:05,070 activation where one of the X chromosomes 77 00:05:05,070 --> 00:05:06,940 is largely transcriptionally silenced. 78 00:05:06,940 --> 00:05:10,260 And so for people that have two or three or four X chromosomes 79 00:05:10,260 --> 00:05:12,150 generally have one or two or three 80 00:05:12,150 --> 00:05:15,510 of these actually silenced so that you only 81 00:05:15,510 --> 00:05:17,820 have expression off of one, and you can essentially 82 00:05:17,820 --> 00:05:18,960 regulate dosage. 83 00:05:18,960 --> 00:05:22,350 And dosage compensation in the sex chromosomes 84 00:05:22,350 --> 00:05:24,720 is a really interesting thing, sort of, 85 00:05:24,720 --> 00:05:27,330 how that works overall. 86 00:05:27,330 --> 00:05:37,230 So lastly, let me just introduce this issue of aneuploidy 87 00:05:37,230 --> 00:05:42,900 and development, and let's think about having a gamete that 88 00:05:42,900 --> 00:05:49,220 has two chromosome 15s, right. 89 00:05:49,220 --> 00:05:52,820 And this would be from a male, and then we 90 00:05:52,820 --> 00:06:00,230 have a female gamete that has the appropriate just 91 00:06:00,230 --> 00:06:02,690 one copy of chromosome 15. 92 00:06:02,690 --> 00:06:05,990 You'd have fertilization here. 93 00:06:05,990 --> 00:06:10,150 You have a resulting embryo, and this resulting embryo 94 00:06:10,150 --> 00:06:16,920 has three copies of chromosome 15, right. 95 00:06:16,920 --> 00:06:18,540 Now one of the ways that this can 96 00:06:18,540 --> 00:06:21,300 be dealt with during development to actually result 97 00:06:21,300 --> 00:06:25,470 in a viable offspring-- because trisomy 15 does not 98 00:06:25,470 --> 00:06:28,290 result in a viable pregnancy-- is that you can actually 99 00:06:28,290 --> 00:06:33,938 lose one of these chromosomes during development, very early 100 00:06:33,938 --> 00:06:35,230 in development actually, right. 101 00:06:35,230 --> 00:06:44,190 So you can get three different possible offspring, 102 00:06:44,190 --> 00:06:52,020 one with two chromosomes from dad 103 00:06:52,020 --> 00:06:55,460 and the other with a chromosome from dad and a chromosome 104 00:06:55,460 --> 00:06:57,110 from mom. 105 00:06:57,110 --> 00:07:06,500 Do you think it matters which of these outcomes exist? 106 00:07:06,500 --> 00:07:11,980 107 00:07:11,980 --> 00:07:14,170 Any guesses? 108 00:07:14,170 --> 00:07:16,560 Yes? 109 00:07:16,560 --> 00:07:17,060 No? 110 00:07:17,060 --> 00:07:18,458 Two possibilities? 111 00:07:18,458 --> 00:07:21,270 112 00:07:21,270 --> 00:07:24,080 It does matter actually so. 113 00:07:24,080 --> 00:07:31,260 If you have two chromosomes from a parent, a father or a mother, 114 00:07:31,260 --> 00:07:38,470 you had what's called uniparental disomy, right, 115 00:07:38,470 --> 00:07:40,780 meaning you just got two chromosomes, 116 00:07:40,780 --> 00:07:42,790 disomes from one parent, right. 117 00:07:42,790 --> 00:07:45,700 And this matters in the context of a number of conditions 118 00:07:45,700 --> 00:07:47,290 called imprinting disorders. 119 00:07:47,290 --> 00:07:50,650 Now interestingly, you have differential gene expression 120 00:07:50,650 --> 00:07:53,050 depending upon the alleles that you inherit from your mom 121 00:07:53,050 --> 00:07:56,200 or your dad for some genes, a subset of genes, 122 00:07:56,200 --> 00:08:00,950 probably less than 50 genes in people. 123 00:08:00,950 --> 00:08:04,480 And so sometimes a gene that you inherit from your father 124 00:08:04,480 --> 00:08:09,010 is turned on, but the maternal allele is turned off, right. 125 00:08:09,010 --> 00:08:12,040 And so if you have two genes that are turned on 126 00:08:12,040 --> 00:08:14,410 or two genes that are turned off, 127 00:08:14,410 --> 00:08:22,840 you have what's called an imprinting disorder, right. 128 00:08:22,840 --> 00:08:29,290 And in the case of chromosome 15, 129 00:08:29,290 --> 00:08:40,580 you have Angelman syndrome, which is actually 130 00:08:40,580 --> 00:08:44,620 a very severe syndrome that has a number 131 00:08:44,620 --> 00:08:45,950 of different phenotypes. 132 00:08:45,950 --> 00:08:48,940 So the genes that you inherit from both your parents 133 00:08:48,940 --> 00:08:50,830 are actually differently regulated. 134 00:08:50,830 --> 00:08:53,560 You need to actually have a maternal and a paternal allele 135 00:08:53,560 --> 00:09:00,010 to have appropriate dosing in the embryo. 136 00:09:00,010 --> 00:09:02,080 And there are lots of really weird explanations, 137 00:09:02,080 --> 00:09:06,280 anthropological explanations for why males and females have 138 00:09:06,280 --> 00:09:09,130 different genes off and on. 139 00:09:09,130 --> 00:09:11,080 There are ideas of sexual antagonism 140 00:09:11,080 --> 00:09:14,860 that are from fly studies, and I'd 141 00:09:14,860 --> 00:09:16,990 be happy to tell you about some of these 142 00:09:16,990 --> 00:09:19,970 if you're interested, but know this does occur. 143 00:09:19,970 --> 00:09:23,410 So on Wednesday, we're actually going 144 00:09:23,410 --> 00:09:25,990 to start talking about this issue of recombination 145 00:09:25,990 --> 00:09:30,160 and how we can link two genes together and think 146 00:09:30,160 --> 00:09:31,840 about how this is occurring in meiosis 147 00:09:31,840 --> 00:09:34,030 and how we can use this to actually map 148 00:09:34,030 --> 00:09:37,140 the fine location of different genes. 10974

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