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These are the user uploaded subtitles that are being translated: 0 00:00:00,000 --> 00:00:00,905 1 00:00:00,905 --> 00:00:02,510 MICHAEL HEMANN: Today, we're going 2 00:00:02,510 --> 00:00:07,660 to talk about chromosomes. 3 00:00:07,660 --> 00:00:11,290 We're going to talk about mitosis and meiosis. 4 00:00:11,290 --> 00:00:14,080 And it's really an attempt to start 5 00:00:14,080 --> 00:00:19,880 placing genes in particular places in the genome. 6 00:00:19,880 --> 00:00:21,530 So in the past number of lectures, 7 00:00:21,530 --> 00:00:23,650 we've been talking about the gene, 8 00:00:23,650 --> 00:00:27,370 essentially, as a unit of function and phenotype, 9 00:00:27,370 --> 00:00:29,762 looking at pedigrees and crosses, 10 00:00:29,762 --> 00:00:31,720 and learning what we could learn without really 11 00:00:31,720 --> 00:00:35,380 having any concept of what a gene is or where it is. 12 00:00:35,380 --> 00:00:38,660 Now we're going to start placing genes within the genome. 13 00:00:38,660 --> 00:00:39,800 And so why do we do that? 14 00:00:39,800 --> 00:00:44,110 We do that because we actually want to be able to map the gene 15 00:00:44,110 --> 00:00:46,090 and identify the alteration. 16 00:00:46,090 --> 00:00:49,570 We want, in the end, to be able to sequence the gene 17 00:00:49,570 --> 00:00:51,790 to understand, what is the etiology of the phenotype 18 00:00:51,790 --> 00:00:53,500 that we're looking at? 19 00:00:53,500 --> 00:00:55,630 That tells us about the molecular mechanisms 20 00:00:55,630 --> 00:00:57,430 by which it's doing what it's doing 21 00:00:57,430 --> 00:01:00,670 and also potential therapeutic options 22 00:01:00,670 --> 00:01:03,550 for what we can do about it if we don't like the phenotype 23 00:01:03,550 --> 00:01:04,390 that we're seeing. 24 00:01:04,390 --> 00:01:06,130 So it really starts with the ability 25 00:01:06,130 --> 00:01:11,110 to map a particular phenotype to a particular place 26 00:01:11,110 --> 00:01:13,670 in the genome. 27 00:01:13,670 --> 00:01:18,430 And so let's start by thinking about the kinds of crosses 28 00:01:18,430 --> 00:01:20,810 that we've been working on recently. 29 00:01:20,810 --> 00:01:23,860 So let's just say that we have a cross that's 30 00:01:23,860 --> 00:01:33,670 between true-breeding wild-type organisms of some type 31 00:01:33,670 --> 00:01:37,640 and a true-breeding homozygous recessive. 32 00:01:37,640 --> 00:01:40,270 So let's say there are two different traits, so 33 00:01:40,270 --> 00:01:44,800 two distinct phenotypes, that are both 34 00:01:44,800 --> 00:01:48,310 caused by being recessive homozygous 35 00:01:48,310 --> 00:01:49,660 for a particular allele. 36 00:01:49,660 --> 00:01:51,730 So the little a, little a, little b, little b 37 00:01:51,730 --> 00:01:53,060 have a different phenotype. 38 00:01:53,060 --> 00:01:56,860 So we can cross these organisms together, and we get an F1. 39 00:01:56,860 --> 00:02:03,070 And the F1's are all heterozygous at this locus. 40 00:02:03,070 --> 00:02:07,270 And we can cross these heterozygotes together 41 00:02:07,270 --> 00:02:11,820 and get an F2 generation. 42 00:02:11,820 --> 00:02:14,500 And this F2 generation, as we've talked about before, 43 00:02:14,500 --> 00:02:18,210 has this phenotypic ratio of 9 to 3 to 3 to 1, 44 00:02:18,210 --> 00:02:20,730 where nine would be wild type, three 45 00:02:20,730 --> 00:02:23,850 would show one of the mutant phenotypes. 46 00:02:23,850 --> 00:02:25,590 If these are independent traits, three 47 00:02:25,590 --> 00:02:27,120 would show the other trait. 48 00:02:27,120 --> 00:02:29,310 And one of them, one out of 16, would 49 00:02:29,310 --> 00:02:31,320 show both of these traits. 50 00:02:31,320 --> 00:02:38,750 And so one of the key ways of examining this F1 generation, 51 00:02:38,750 --> 00:02:40,970 these heterozygotes, and the gametes 52 00:02:40,970 --> 00:02:44,840 that they're actually generating to go into the F2 generation 53 00:02:44,840 --> 00:02:47,280 is to perform a test cross. 54 00:02:47,280 --> 00:02:50,120 And so a test cross is generally a cross 55 00:02:50,120 --> 00:02:51,810 to a homozygous recessive. 56 00:02:51,810 --> 00:02:56,230 So if we take these F1 heterozygotes 57 00:02:56,230 --> 00:03:03,230 and we cross them with homozygous recessives, 58 00:03:03,230 --> 00:03:07,940 we can actually identify in this cross all of the gametes 59 00:03:07,940 --> 00:03:10,070 that this F1 is generating. 60 00:03:10,070 --> 00:03:12,530 And this is going to be really key in understanding 61 00:03:12,530 --> 00:03:15,380 whether there's truly independent assortment of genes 62 00:03:15,380 --> 00:03:18,980 or whether these genes are in close approximation with one 63 00:03:18,980 --> 00:03:22,220 another on the same chromosome, whether they're linked. 64 00:03:22,220 --> 00:03:26,660 So this F1 heterozygote-- 65 00:03:26,660 --> 00:03:29,390 double heterozygote-- can generate four different kinds 66 00:03:29,390 --> 00:03:30,800 of gametes. 67 00:03:30,800 --> 00:03:35,860 It can generate big A, big B. They can 68 00:03:35,860 --> 00:03:39,760 generate little a, little b. 69 00:03:39,760 --> 00:03:42,550 They can generate big A, little b. 70 00:03:42,550 --> 00:03:45,910 Or they can generate little a, big B. 71 00:03:45,910 --> 00:03:48,910 So these are the four kinds of gametes that this F1 72 00:03:48,910 --> 00:03:50,440 heterozygote is generating. 73 00:03:50,440 --> 00:03:56,840 And we can designate these, basically, in two groups. 74 00:03:56,840 --> 00:03:58,430 One of them is parental. 75 00:03:58,430 --> 00:04:01,010 And parental simply means that these were the alleles 76 00:04:01,010 --> 00:04:05,630 that they inherited from one of these first-generation parents. 77 00:04:05,630 --> 00:04:06,830 So they could have gotten-- 78 00:04:06,830 --> 00:04:09,110 the only alleles you can generate from this parent 79 00:04:09,110 --> 00:04:10,970 is big A, big B. The only alleles 80 00:04:10,970 --> 00:04:17,089 you can generate from this parent are little a, little b. 81 00:04:17,089 --> 00:04:20,690 So these we call parental. 82 00:04:20,690 --> 00:04:23,390 And the other two-- big A, little b and little a, 83 00:04:23,390 --> 00:04:27,200 big B-- we're going to call recombinant. 84 00:04:27,200 --> 00:04:33,290 Because it's some mixture of these first-generation alleles. 85 00:04:33,290 --> 00:04:38,660 It means that they got a big A from one of the parents, 86 00:04:38,660 --> 00:04:41,000 or they're passing on one big A from one 87 00:04:41,000 --> 00:04:43,920 of the parents and a small b from the other parent. 88 00:04:43,920 --> 00:04:46,010 So somehow, these are recombining 89 00:04:46,010 --> 00:04:48,110 in their germ cells. 90 00:04:48,110 --> 00:04:50,000 And they'll produce, when we cross them 91 00:04:50,000 --> 00:04:53,420 with the homozygous recessive in the test cross, 92 00:04:53,420 --> 00:04:56,900 they'll produce four kinds of progeny. 93 00:04:56,900 --> 00:05:04,415 One is big A, little a, big B, little b. 94 00:05:04,415 --> 00:05:07,340 It's just if you actually cross this with little a, little b. 95 00:05:07,340 --> 00:05:11,315 Another will be little a, little a, little b, little b. 96 00:05:11,315 --> 00:05:16,040 The other will be big A, little a, little b, little b. 97 00:05:16,040 --> 00:05:20,570 And the final will be little a, little a, big B, little b. 98 00:05:20,570 --> 00:05:22,850 The cool thing with a test cross is you can actually 99 00:05:22,850 --> 00:05:23,930 see all of these things. 100 00:05:23,930 --> 00:05:26,270 They all look different. 101 00:05:26,270 --> 00:05:29,040 So little a, little a, little b, little b is homozygous 102 00:05:29,040 --> 00:05:29,540 recessive. 103 00:05:29,540 --> 00:05:31,040 They have two traits. 104 00:05:31,040 --> 00:05:34,250 Big A, little b, big B, little b, they're totally wild type. 105 00:05:34,250 --> 00:05:40,230 And in a test cross, we'd expect, 106 00:05:40,230 --> 00:05:42,430 if they are independently segregating genes, 107 00:05:42,430 --> 00:05:48,400 that we're going to have a ratio here of 1 to 1 to 1 to 1, 108 00:05:48,400 --> 00:05:50,800 so equal representation for all of these. 109 00:05:50,800 --> 00:05:53,050 And this is really the hallmark of the segregation 110 00:05:53,050 --> 00:05:55,870 of genes that are on distinct chromosomes. 111 00:05:55,870 --> 00:05:58,625 It suggests that the genes, in fact, are not linked together. 112 00:05:58,625 --> 00:05:59,750 They're not close together. 113 00:05:59,750 --> 00:06:02,480 But they're actually on distinct chromosomes. 114 00:06:02,480 --> 00:06:04,240 So again, today, we're going to talk 115 00:06:04,240 --> 00:06:07,840 about chromosome segregation and what that looks like 116 00:06:07,840 --> 00:06:09,400 and what it means and perhaps what 117 00:06:09,400 --> 00:06:12,570 happens when it goes wrong. 8960

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