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Would you like to inspect the original subtitles? These are the user uploaded subtitles that are being translated: 0 00:00:00,000 --> 00:00:01,417 MICHAEL HEMANN: Today, we're going 1 00:00:01,417 --> 00:00:09,870 to continue our discussion on mapping genes in the genome. 2 00:00:09,870 --> 00:00:13,860 We talked about mapping phenotypes relative to one 3 00:00:13,860 --> 00:00:20,370 another, which we can do, and we can 4 00:00:20,370 --> 00:00:25,200 identify a genetic distance, which correlates roughly 5 00:00:25,200 --> 00:00:28,470 with the physical distance between two different genes. 6 00:00:28,470 --> 00:00:32,040 But we noticed that this relationship breaks down 7 00:00:32,040 --> 00:00:35,520 at a long distance, and that really the longest 8 00:00:35,520 --> 00:00:39,090 distance that we can measure between two genes 9 00:00:39,090 --> 00:00:40,680 is about 50 centimorgans. 10 00:00:40,680 --> 00:00:43,170 It's actually less than 50 centimorgans, 11 00:00:43,170 --> 00:00:45,030 because we're getting multiple recombination 12 00:00:45,030 --> 00:00:46,470 events between these two genes. 13 00:00:46,470 --> 00:00:51,990 And so we are frequently underestimating distances. 14 00:00:51,990 --> 00:00:54,965 And we're not able to do fine mapping the way 15 00:00:54,965 --> 00:00:57,090 that we need to, because the whole purpose of doing 16 00:00:57,090 --> 00:00:59,790 this is we actually want to find a gene that we're 17 00:00:59,790 --> 00:01:02,890 looking for that has some alteration that we care about. 18 00:01:02,890 --> 00:01:06,450 So today we're going to talk about how we do fine mapping 19 00:01:06,450 --> 00:01:08,640 and how we use DNA markers to actually do 20 00:01:08,640 --> 00:01:11,860 that mapping in place of clear phenotypes. 21 00:01:11,860 --> 00:01:15,360 And so again, an example of the problem that we have 22 00:01:15,360 --> 00:01:17,590 is that we have intervals in the genome. 23 00:01:17,590 --> 00:01:22,230 So we have an interval here that's about nine centimorgans. 24 00:01:22,230 --> 00:01:26,010 And so that's roughly about three megabases in Drosophila. 25 00:01:26,010 --> 00:01:29,970 26 00:01:29,970 --> 00:01:32,460 So that's three million bases, and so that 27 00:01:32,460 --> 00:01:35,290 would be about 30 genes. 28 00:01:35,290 --> 00:01:37,038 So we're looking for an alteration, 29 00:01:37,038 --> 00:01:38,830 and we have a choice of 30 different genes. 30 00:01:38,830 --> 00:01:40,900 And that's really too many, again, 31 00:01:40,900 --> 00:01:43,180 when we want to have a good sense of where to look. 32 00:01:43,180 --> 00:01:45,730 And this is an even bigger problem 33 00:01:45,730 --> 00:01:47,440 when we talk about people, because we 34 00:01:47,440 --> 00:01:49,300 can't do crosses between people, and we 35 00:01:49,300 --> 00:01:52,930 can't look at phenotypes and the segregation 36 00:01:52,930 --> 00:01:55,322 of different phenotypes in clear ways. 37 00:01:55,322 --> 00:01:57,280 There are some ways that we'll talk about later 38 00:01:57,280 --> 00:01:58,655 on in the class where we can look 39 00:01:58,655 --> 00:02:00,790 at some fine mapping in phenotypes, 40 00:02:00,790 --> 00:02:04,360 but we need a strategy to do fine resolution mapping when 41 00:02:04,360 --> 00:02:07,570 we do crosses that allows us to identify 42 00:02:07,570 --> 00:02:09,550 very specific regions of the genome 43 00:02:09,550 --> 00:02:11,500 where we want to have a deep dive 44 00:02:11,500 --> 00:02:14,110 to look for the alterations, and then 45 00:02:14,110 --> 00:02:16,090 do functional studies to try to identify 46 00:02:16,090 --> 00:02:18,880 whether the alterations that we find account for the phenotypes 47 00:02:18,880 --> 00:02:20,150 that we see. 48 00:02:20,150 --> 00:02:25,480 So the real challenge is how do we do fine mapping? 49 00:02:25,480 --> 00:02:29,320 50 00:02:29,320 --> 00:02:33,970 So high resolution mapping in the genome. 51 00:02:33,970 --> 00:02:40,540 And the approach that we take is to use DNA markers. 52 00:02:40,540 --> 00:02:43,030 So what are DNA markers? 53 00:02:43,030 --> 00:02:48,730 Well, DNA markers are essentially just signposts 54 00:02:48,730 --> 00:02:49,840 in the genome. 55 00:02:49,840 --> 00:02:52,330 They're basically mile markers. 56 00:02:52,330 --> 00:02:56,720 They may actually have no functional relevance at all. 57 00:02:56,720 --> 00:03:00,220 They just define specific places in the genome 58 00:03:00,220 --> 00:03:03,100 that we can map next to. 59 00:03:03,100 --> 00:03:10,610 So you can really think of DNA markers 60 00:03:10,610 --> 00:03:13,240 as places in the genome. 61 00:03:13,240 --> 00:03:18,000 4630

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