1 00:00:00,000 --> 00:00:00,990 [Instructor] All right, you made it 2 00:00:00,990 --> 00:00:04,080 to the last lecture in module five. 3 00:00:04,080 --> 00:00:07,320 Well, here we're gonna talk about some exceptions 4 00:00:07,320 --> 00:00:08,610 to the rule, as you know. 5 00:00:08,610 --> 00:00:11,103 I mean, I think genetics is, 6 00:00:12,420 --> 00:00:14,700 it's an interesting field of study 7 00:00:14,700 --> 00:00:17,370 because there are so many rules 8 00:00:17,370 --> 00:00:19,560 and it can be quite black and white, 9 00:00:19,560 --> 00:00:22,560 but then for every rule, there's at least one exception. 10 00:00:22,560 --> 00:00:24,570 And sometimes those are pretty important 11 00:00:24,570 --> 00:00:26,220 and you'll actually see them quite often. 12 00:00:26,220 --> 00:00:31,220 And so, as clear-cut as it was 13 00:00:31,230 --> 00:00:33,720 to explain Mendelian inheritance, 14 00:00:33,720 --> 00:00:35,370 and you can draw up these Punnett squares 15 00:00:35,370 --> 00:00:37,570 and that's wonderful, you can estimate risk, 16 00:00:38,460 --> 00:00:40,470 there are exceptions to each of those 17 00:00:40,470 --> 00:00:42,330 and it can become kind of confusing at times 18 00:00:42,330 --> 00:00:43,800 when you're looking at a pedigree and you're thinking, 19 00:00:43,800 --> 00:00:45,840 well, according to Mendelian inheritance, 20 00:00:45,840 --> 00:00:48,057 it should look like this, but it actually looks like that. 21 00:00:48,057 --> 00:00:51,330 And so, trying to understand why that might be the case 22 00:00:51,330 --> 00:00:52,800 where there would be some exceptions 23 00:00:52,800 --> 00:00:54,030 and what those exceptions are 24 00:00:54,030 --> 00:00:55,680 and giving you a few examples of that. 25 00:00:55,680 --> 00:00:58,110 So, that's the goal for this lecture. 26 00:00:58,110 --> 00:00:59,430 So, along with that, there's gonna be 27 00:00:59,430 --> 00:01:01,500 a number of different terms I'm going to use 28 00:01:01,500 --> 00:01:03,720 and wanted to provide you with a list of definitions 29 00:01:03,720 --> 00:01:05,760 right up here at the front. 30 00:01:05,760 --> 00:01:07,380 And I'm actually not gonna talk 31 00:01:07,380 --> 00:01:08,700 through each of these right now 32 00:01:08,700 --> 00:01:10,050 because I'm going to talk through each of them 33 00:01:10,050 --> 00:01:12,870 as I go through them in their slides, 34 00:01:12,870 --> 00:01:14,670 but wanted you to have a list 35 00:01:14,670 --> 00:01:16,650 so you can refer back to those, 36 00:01:16,650 --> 00:01:19,350 maybe keep it handy beside you 37 00:01:19,350 --> 00:01:20,610 if I'm starting to use a term 38 00:01:20,610 --> 00:01:22,020 that falls into one of these categories, 39 00:01:22,020 --> 00:01:23,720 you can look it up rather quickly. 40 00:01:24,960 --> 00:01:27,720 Let's first talk about dominance relationships. 41 00:01:27,720 --> 00:01:30,810 So, we categorized dominant or recessive 42 00:01:30,810 --> 00:01:33,120 as you have two alleles, 43 00:01:33,120 --> 00:01:36,270 and one of them is going to be dominant to the other, right? 44 00:01:36,270 --> 00:01:38,580 And it's the dominant one that you actually, 45 00:01:38,580 --> 00:01:40,170 that actually impacts the phenotype. 46 00:01:40,170 --> 00:01:43,740 So, you see that the phenotype come through. 47 00:01:43,740 --> 00:01:44,880 So, if it's recessive, 48 00:01:44,880 --> 00:01:46,080 the only way you're seeing the phenotype 49 00:01:46,080 --> 00:01:50,670 is if both alleles are the same recessive allele. 50 00:01:50,670 --> 00:01:55,290 Well, that, and that is the case the majority of the time. 51 00:01:55,290 --> 00:01:56,940 There are some exceptions to that, 52 00:01:56,940 --> 00:01:58,800 and you may hear these terms, 53 00:01:58,800 --> 00:02:00,900 and I just wanna make sure that it's clear 54 00:02:00,900 --> 00:02:02,520 what they're referring to. 55 00:02:02,520 --> 00:02:04,800 And these are just different dominance relationships. 56 00:02:04,800 --> 00:02:06,140 So, yes, dominant recessive 57 00:02:06,140 --> 00:02:08,640 is the main kind of relationship you'll see 58 00:02:08,640 --> 00:02:13,080 for single gene disorders or for single gene traits, 59 00:02:13,080 --> 00:02:15,720 but there are some others that do come up, 60 00:02:15,720 --> 00:02:18,210 and these would include incomplete dominance 61 00:02:18,210 --> 00:02:19,950 and codominance. 62 00:02:19,950 --> 00:02:21,630 So, what do I mean by that? 63 00:02:21,630 --> 00:02:24,840 Well, some way to visualize it that I find helpful 64 00:02:24,840 --> 00:02:29,840 is actually just sort of looking at colors as a phenotype, 65 00:02:30,840 --> 00:02:35,840 and actually several of these kinds of genetic phenomena 66 00:02:36,060 --> 00:02:37,600 that we're going to talk about in this lecture 67 00:02:37,600 --> 00:02:42,600 were first categorized by looking in plants and in flowers 68 00:02:43,500 --> 00:02:48,380 that were expressing different types of traits. 69 00:02:48,380 --> 00:02:51,840 It could easily be logged. 70 00:02:51,840 --> 00:02:54,570 So, you could look at a plant and its flower 71 00:02:54,570 --> 00:02:56,370 and see, well, what is the color of the flower? 72 00:02:56,370 --> 00:02:57,540 What is the size, the shape? 73 00:02:57,540 --> 00:03:02,540 And so, plants were used to help us better understand 74 00:03:02,670 --> 00:03:04,860 some of these genetic concepts. 75 00:03:04,860 --> 00:03:08,460 Plus, plants don't generally complain when you cross them, 76 00:03:08,460 --> 00:03:09,293 and when you say, 77 00:03:09,293 --> 00:03:10,660 I'm going to cross this plant with this plant, 78 00:03:10,660 --> 00:03:13,260 they don't put up much of a fight. 79 00:03:13,260 --> 00:03:14,430 They're just going to go with it. 80 00:03:14,430 --> 00:03:15,450 Humans, on the other hand, 81 00:03:15,450 --> 00:03:19,410 it's notoriously difficult to get two humans to cross 82 00:03:19,410 --> 00:03:20,490 just to see what happens, 83 00:03:20,490 --> 00:03:22,360 and I'm pretty sure none of us would want to do that. 84 00:03:22,360 --> 00:03:26,280 So, a lot of what we know, we know initially from plants. 85 00:03:26,280 --> 00:03:29,850 And so, I find this to be a helpful way to demonstrate it 86 00:03:29,850 --> 00:03:33,840 just by looking at color as a type of phenotype output, 87 00:03:33,840 --> 00:03:36,270 but you can apply this to different diseases 88 00:03:36,270 --> 00:03:38,040 and other human traits as well, 89 00:03:38,040 --> 00:03:40,440 and I'll give you some examples of those 90 00:03:40,440 --> 00:03:41,880 in some subsequent slides. 91 00:03:41,880 --> 00:03:45,030 But just to get us all on the same page here, 92 00:03:45,030 --> 00:03:47,220 when you see different dominance relationships, 93 00:03:47,220 --> 00:03:51,330 you see those primarily when you have a cross 94 00:03:51,330 --> 00:03:55,290 between two parents that are both homozygous, right? 95 00:03:55,290 --> 00:04:00,290 So, both of their alleles are the same, 96 00:04:00,540 --> 00:04:04,740 and the two parents are different from one another. 97 00:04:04,740 --> 00:04:06,690 So, this one parent is homozygous, 98 00:04:06,690 --> 00:04:08,520 let's say, for the A1 allele, 99 00:04:08,520 --> 00:04:09,510 if that was one of the alleles. 100 00:04:09,510 --> 00:04:11,880 Let's say the other allele is the A2 allele, 101 00:04:11,880 --> 00:04:12,780 and we're calling them this 102 00:04:12,780 --> 00:04:14,160 instead of uppercase and lowercase, 103 00:04:14,160 --> 00:04:17,940 because, let's say, for the sake of argument, 104 00:04:17,940 --> 00:04:20,520 we don't actually know which of these two alleles, 105 00:04:20,520 --> 00:04:22,890 the green allele or the white allele, 106 00:04:22,890 --> 00:04:25,590 is actually going to be dominant to the other one. 107 00:04:25,590 --> 00:04:26,820 So, what we're just going to designate them 108 00:04:26,820 --> 00:04:31,593 as A1 for the white one, and A2 is the green allele, okay? 109 00:04:32,520 --> 00:04:34,590 If you had a cross between, 110 00:04:34,590 --> 00:04:36,150 again, let's think of this in terms of plants, 111 00:04:36,150 --> 00:04:37,020 because it's going to sound weird 112 00:04:37,020 --> 00:04:38,730 if we start thinking that I'm saying 113 00:04:38,730 --> 00:04:41,100 we're crossing two humans together. 114 00:04:41,100 --> 00:04:43,230 So, let's just assume we're talking about plants here, okay? 115 00:04:43,230 --> 00:04:46,260 So, let's say we're crossing a white flower plant 116 00:04:46,260 --> 00:04:47,940 with a green flower plant, 117 00:04:47,940 --> 00:04:52,800 and the resulting cross gives us a offspring or child, 118 00:04:52,800 --> 00:04:55,800 if we're thinking about humans, that is white, 119 00:04:55,800 --> 00:04:58,890 that demonstrates the phenotype 120 00:04:58,890 --> 00:05:02,070 that is associated with one of the two parents. 121 00:05:02,070 --> 00:05:04,800 That tells us that A1 allele is dominant to A2, 122 00:05:04,800 --> 00:05:06,060 just straight up dominant, 123 00:05:06,060 --> 00:05:07,530 just like what we've been talking about 124 00:05:07,530 --> 00:05:09,300 in the previous lecture. 125 00:05:09,300 --> 00:05:12,000 If, on the other hand, you cross the white flower plant 126 00:05:12,000 --> 00:05:12,833 with the green flower plant, 127 00:05:12,833 --> 00:05:14,910 and you get a green flower offspring, 128 00:05:14,910 --> 00:05:16,620 that tells us that the A2 allele, 129 00:05:16,620 --> 00:05:20,880 which the green flower parent was homozygous for, 130 00:05:20,880 --> 00:05:24,030 is actually dominant to the A1 allele, 131 00:05:24,030 --> 00:05:28,500 or the allele that the white flower parent plant had. 132 00:05:28,500 --> 00:05:29,610 So, we know that these two, 133 00:05:29,610 --> 00:05:31,500 these first two cases are complete dominants, 134 00:05:31,500 --> 00:05:33,030 and that's the sort of the traditional 135 00:05:33,030 --> 00:05:34,743 dominant recessive relationship. 136 00:05:36,150 --> 00:05:38,200 If, however, you cross a white flower 137 00:05:38,200 --> 00:05:40,290 with a green flower plant, 138 00:05:40,290 --> 00:05:43,470 and you get some color in between white and green, 139 00:05:43,470 --> 00:05:47,070 so like this sort of yellowish, light green color, 140 00:05:47,070 --> 00:05:48,630 so it doesn't look like either one 141 00:05:48,630 --> 00:05:51,840 of the two original homozygous parents. 142 00:05:51,840 --> 00:05:54,090 Well, it's sort of a blended phenotype, 143 00:05:54,090 --> 00:05:57,120 so the phenotype looks like sort of a spectrum, 144 00:05:57,120 --> 00:06:00,000 it's somewhere in between the two parents, 145 00:06:00,000 --> 00:06:02,430 and that's an incomplete dominance, 146 00:06:02,430 --> 00:06:04,470 so that's known as incomplete dominance. 147 00:06:04,470 --> 00:06:06,810 Codominant would be if you're crossing 148 00:06:06,810 --> 00:06:08,790 a white flower plant with a green flower plant, 149 00:06:08,790 --> 00:06:12,360 and you get a flower from the offspring 150 00:06:12,360 --> 00:06:14,820 that has green stripes and white stripes, 151 00:06:14,820 --> 00:06:17,760 so portions of it look just like one parent, 152 00:06:17,760 --> 00:06:20,550 and other portions of it look just like the other parent, 153 00:06:20,550 --> 00:06:23,640 so you actually have distinct domains, parts of each, 154 00:06:23,640 --> 00:06:25,890 that represent each of the two, 155 00:06:25,890 --> 00:06:28,410 look like each of the two homozygous parents. 156 00:06:28,410 --> 00:06:30,660 That's codominant, so they're dominant together, 157 00:06:30,660 --> 00:06:34,800 like they're both sort of demonstrating 158 00:06:34,800 --> 00:06:38,643 a type of dominance in different regions of the offspring. 159 00:06:39,630 --> 00:06:42,720 Basically, you're able to see the phenotype 160 00:06:42,720 --> 00:06:45,990 of both parents in the offspring. 161 00:06:45,990 --> 00:06:46,950 All right, let's take a peek 162 00:06:46,950 --> 00:06:48,980 at what this actually looks like in humans. 163 00:06:48,980 --> 00:06:52,170 Moving from plants to humans, so in codominance, 164 00:06:52,170 --> 00:06:55,020 both alleles individually contribute to the phenotype, 165 00:06:55,020 --> 00:06:57,940 and you can see both of those in the phenotype. 166 00:06:57,940 --> 00:07:01,590 The classic example of this is blood type, right? 167 00:07:01,590 --> 00:07:05,730 So you know there's type A, type B, AB, and O, 168 00:07:05,730 --> 00:07:09,510 so you either have the A allele, a B allele, 169 00:07:09,510 --> 00:07:12,540 or an O allele, and some combination of those two, 170 00:07:12,540 --> 00:07:16,050 and individuals that have an A allele, 171 00:07:16,050 --> 00:07:18,120 A is dominant to the O allele, 172 00:07:18,120 --> 00:07:19,863 so they would have type A blood. 173 00:07:20,880 --> 00:07:24,497 If someone has a B allele, a B is dominant to the O allele. 174 00:07:26,820 --> 00:07:29,910 O is basically like a fully recessive allele. 175 00:07:29,910 --> 00:07:32,380 Then that person would have type B blood 176 00:07:32,380 --> 00:07:36,660 if their genotype is B-O. 177 00:07:36,660 --> 00:07:41,100 Now let's look at a cross between an A-O and B-O individual, 178 00:07:41,100 --> 00:07:45,270 and what we see is that you get A-O offspring, right, 179 00:07:45,270 --> 00:07:48,720 and that's going to be type A because A is dominant to O. 180 00:07:48,720 --> 00:07:53,700 You get children that have B-O genotype, 181 00:07:53,700 --> 00:07:55,650 and they would be type B blood, 182 00:07:55,650 --> 00:07:57,810 and then those that are O-O, 183 00:07:57,810 --> 00:07:59,160 so that would be type O blood, 184 00:07:59,160 --> 00:08:01,380 again, because O is recessive to both A and B. 185 00:08:01,380 --> 00:08:02,610 If you have two copies of O, 186 00:08:02,610 --> 00:08:04,140 then they're going to have type O blood. 187 00:08:04,140 --> 00:08:07,470 A is dominant to O, B is dominant to O, 188 00:08:07,470 --> 00:08:11,160 but what about when you get one of each of the A and B? 189 00:08:11,160 --> 00:08:12,690 Which one wins out? 190 00:08:12,690 --> 00:08:15,900 Well, in this case, there actually isn't a single winner. 191 00:08:15,900 --> 00:08:17,670 They both share dominance. 192 00:08:17,670 --> 00:08:22,110 It's codominant, so you would have blood type A, B, 193 00:08:22,110 --> 00:08:24,120 blood type A, B, and that's going to be caused 194 00:08:24,120 --> 00:08:26,280 by having these two sort of, 195 00:08:26,280 --> 00:08:28,530 you can think of it as like fighters, 196 00:08:28,530 --> 00:08:31,260 and those dominant alleles will knock out 197 00:08:31,260 --> 00:08:32,097 the recessive allele, 198 00:08:32,097 --> 00:08:34,440 and so they'll be the last one standing, right? 199 00:08:34,440 --> 00:08:37,470 So if you have A and O, it's like A versus O, 200 00:08:37,470 --> 00:08:38,400 A is going to win out. 201 00:08:38,400 --> 00:08:40,440 If you have B versus O, B is going to win out 202 00:08:40,440 --> 00:08:41,550 in terms of the phenotype, 203 00:08:41,550 --> 00:08:43,110 and so that's going to be dominant. 204 00:08:43,110 --> 00:08:46,530 If you have A and B, it's like having fighters 205 00:08:46,530 --> 00:08:48,960 that are both equally good as one another, 206 00:08:48,960 --> 00:08:52,120 and so they just kind of both exist together. 207 00:08:52,120 --> 00:08:54,750 Neither one ever really knocks out the other, 208 00:08:54,750 --> 00:08:56,610 and you see both together. 209 00:08:56,610 --> 00:08:58,350 That's giving you something 210 00:08:58,350 --> 00:09:00,420 that is a codominant relationship. 211 00:09:00,420 --> 00:09:02,700 Okay, so we kind of talked through that, 212 00:09:02,700 --> 00:09:05,550 and again, A and B alleles are codominants. 213 00:09:05,550 --> 00:09:09,090 So the dominance relationship is established 214 00:09:09,090 --> 00:09:11,100 between any two alleles. 215 00:09:11,100 --> 00:09:13,290 You're going to have a relationship established, 216 00:09:13,290 --> 00:09:15,870 and again, like the fighter analogy, 217 00:09:15,870 --> 00:09:18,210 if A is stronger than O, 218 00:09:18,210 --> 00:09:20,580 let's say fighter A is stronger than fighter O, 219 00:09:20,580 --> 00:09:21,413 it's going to knock it out, 220 00:09:21,413 --> 00:09:22,490 and it's going to be dominant to O 221 00:09:22,490 --> 00:09:24,840 in that situation when it's A versus O. 222 00:09:24,840 --> 00:09:26,340 However, when it's A versus B, 223 00:09:26,340 --> 00:09:27,900 or A and B are together, 224 00:09:27,900 --> 00:09:28,980 and they're trying to figure out 225 00:09:28,980 --> 00:09:30,630 which one gets the phenotype, 226 00:09:30,630 --> 00:09:32,100 well, they're both equally strong, 227 00:09:32,100 --> 00:09:35,280 and so they're actually codominant to one another, 228 00:09:35,280 --> 00:09:37,230 and if you have two Os in the ring, right, 229 00:09:37,230 --> 00:09:40,200 if it's O versus O, it's like the lightweight match, 230 00:09:40,200 --> 00:09:44,790 then it's going to be a type O blood type, 231 00:09:44,790 --> 00:09:46,470 and that's going to be your phenotype 232 00:09:46,470 --> 00:09:47,580 because it's recessive. 233 00:09:47,580 --> 00:09:48,840 It doesn't really beat out anything, 234 00:09:48,840 --> 00:09:50,720 but if there's nothing else left to fight it, 235 00:09:50,720 --> 00:09:55,440 if it's just two of the same O in the ring, so to speak, 236 00:09:55,440 --> 00:09:57,720 then you're going to get a blood type of O 237 00:09:57,720 --> 00:09:59,520 because it's recessive. 238 00:09:59,520 --> 00:10:00,750 So just think about that for a little bit. 239 00:10:00,750 --> 00:10:04,830 It's all about relationships between two alleles, 240 00:10:04,830 --> 00:10:07,360 so A is dominant to O, B is dominant to O, 241 00:10:07,360 --> 00:10:09,543 and A and B are codominant to each other. 242 00:10:11,160 --> 00:10:12,480 All right, incomplete dominance. 243 00:10:12,480 --> 00:10:14,070 Let's look at an example of that. 244 00:10:14,070 --> 00:10:16,500 Both alleles contribute to a mixed phenotype. 245 00:10:16,500 --> 00:10:18,540 Disease allele is usually severe 246 00:10:18,540 --> 00:10:20,100 when homozygous and less severe, 247 00:10:20,100 --> 00:10:21,990 but not nonexistent when heterozygous. 248 00:10:21,990 --> 00:10:24,330 An example of this is sickle cell trait. 249 00:10:24,330 --> 00:10:25,830 So if you have an individual, 250 00:10:25,830 --> 00:10:30,830 let's say the father has sickle cell anemia 251 00:10:31,590 --> 00:10:35,850 and the mother is wild type, is not a carrier, 252 00:10:35,850 --> 00:10:37,470 doesn't have the condition, 253 00:10:37,470 --> 00:10:39,780 and let's say they have children with one another. 254 00:10:39,780 --> 00:10:40,740 So what does that mean? 255 00:10:40,740 --> 00:10:42,420 If the mother is wild type, 256 00:10:42,420 --> 00:10:43,650 she does not have a disease allele. 257 00:10:43,650 --> 00:10:45,840 Sickle cell anemia is recessive. 258 00:10:45,840 --> 00:10:48,780 That means the father has both copies are disease allele. 259 00:10:48,780 --> 00:10:50,910 That means all of their children are going to have, 260 00:10:50,910 --> 00:10:52,050 are going to be carriers, right? 261 00:10:52,050 --> 00:10:53,790 So what we define as carriers, 262 00:10:53,790 --> 00:10:58,047 which is they have one dominant wild type allele 263 00:10:58,047 --> 00:11:00,600 and one recessive disease allele. 264 00:11:00,600 --> 00:11:02,580 Well, in the case of sickle cell disease, 265 00:11:02,580 --> 00:11:04,680 it's not quite so cut and dry 266 00:11:04,680 --> 00:11:06,930 as it being a completely recessive condition. 267 00:11:06,930 --> 00:11:10,080 It is indeed, sickle cell anemia is recessive. 268 00:11:10,080 --> 00:11:11,980 So you would have to have both alleles 269 00:11:13,110 --> 00:11:14,670 be the disease allele. 270 00:11:14,670 --> 00:11:17,550 However, there is an intermediate phenotype in the carriers. 271 00:11:17,550 --> 00:11:18,420 These are carriers, 272 00:11:18,420 --> 00:11:20,880 but they're not completely asymptomatic. 273 00:11:20,880 --> 00:11:24,720 In individuals who are carriers for sickle cell disease, 274 00:11:24,720 --> 00:11:26,970 this would be someone who would be diagnosed 275 00:11:26,970 --> 00:11:28,380 having sickle cell trait. 276 00:11:28,380 --> 00:11:32,820 That means that they, under certain stress conditions, 277 00:11:32,820 --> 00:11:35,160 they may actually be symptomatic. 278 00:11:35,160 --> 00:11:39,140 And it can be rather problematic for individuals 279 00:11:40,100 --> 00:11:43,120 who say are participating in athletic events 280 00:11:43,120 --> 00:11:46,300 or under some kind of physical stress 281 00:11:46,300 --> 00:11:48,780 or dehydration. 282 00:11:48,780 --> 00:11:50,880 They might actually start to display 283 00:11:50,880 --> 00:11:55,290 some of the disease phenotype of sickle cell disease. 284 00:11:55,290 --> 00:11:57,690 So they don't actually have full sickle cell disease, 285 00:11:57,690 --> 00:11:59,580 but they might show some symptoms, 286 00:11:59,580 --> 00:12:02,010 some mild symptoms, something in between, right? 287 00:12:02,010 --> 00:12:04,050 So like it's between perfectly healthy 288 00:12:04,050 --> 00:12:06,380 and having sickle cell disease or sickle cell anemia 289 00:12:06,380 --> 00:12:09,150 is this middle place where many of the carriers 290 00:12:09,150 --> 00:12:11,793 actually will be slightly symptomatic. 291 00:12:13,280 --> 00:12:14,580 So this does not, 292 00:12:14,580 --> 00:12:19,040 this fit the definition of fully dominant or recessive. 293 00:12:19,040 --> 00:12:19,873 All right. 294 00:12:19,873 --> 00:12:24,480 Now let's think about a couple of other phenomena. 295 00:12:24,480 --> 00:12:28,620 And we've been talking about one gene, one phenotype. 296 00:12:28,620 --> 00:12:31,200 And that is a really nice and convenient way 297 00:12:31,200 --> 00:12:32,190 to think about it. 298 00:12:32,190 --> 00:12:34,320 However, in reality, there are certain genes 299 00:12:34,320 --> 00:12:38,460 that when mutated can affect multiple different traits 300 00:12:38,460 --> 00:12:40,440 simply because the function of the protein 301 00:12:40,440 --> 00:12:41,340 that's encoded for by the carrier 302 00:12:41,340 --> 00:12:45,060 by that gene is such that it may work 303 00:12:45,060 --> 00:12:47,100 in multiple systems of the body. 304 00:12:47,100 --> 00:12:50,940 It may maybe express at different times in development 305 00:12:50,940 --> 00:12:54,060 and that could lead to multiple different 306 00:12:54,060 --> 00:12:57,300 seemingly unrelated phenotypes. 307 00:12:57,300 --> 00:13:01,830 And one good example of this is phenylketonuria or PKU, 308 00:13:01,830 --> 00:13:06,830 which is one of the more common single gene disorders 309 00:13:06,870 --> 00:13:09,390 that's diagnosed and it's part of newborn screening 310 00:13:09,390 --> 00:13:10,503 to look for it. 311 00:13:11,460 --> 00:13:13,680 It's the results of a mutation in one gene 312 00:13:13,680 --> 00:13:16,800 and this can cause multiple phenotypic traits 313 00:13:16,800 --> 00:13:17,880 that may appear unrelated. 314 00:13:17,880 --> 00:13:20,370 As you can see here on the right-hand side, 315 00:13:20,370 --> 00:13:24,540 this is a young man with untreated phenylketonuria 316 00:13:24,540 --> 00:13:26,880 and he is in a wheelchair. 317 00:13:26,880 --> 00:13:31,710 He also experiences intellectual disability, epilepsy. 318 00:13:31,710 --> 00:13:33,510 He has fair skin. 319 00:13:33,510 --> 00:13:36,870 As you can see down here, a mutation in the PAH gene, 320 00:13:36,870 --> 00:13:40,830 which leads to PKU can result in a number 321 00:13:40,830 --> 00:13:43,800 of different phenotypes that are often characteristic 322 00:13:43,800 --> 00:13:47,520 of untreated PKU. 323 00:13:47,520 --> 00:13:50,700 And this is a really severe condition 324 00:13:50,700 --> 00:13:54,840 that can be treated by a specific diet. 325 00:13:54,840 --> 00:13:56,880 Inheritance still follows Mendelian patterns, 326 00:13:56,880 --> 00:13:59,820 but it is because it is from one gene. 327 00:13:59,820 --> 00:14:03,270 And however, the difficulty can come 328 00:14:03,270 --> 00:14:05,070 from looking at the patient. 329 00:14:05,070 --> 00:14:06,210 That's what you look at as the patient. 330 00:14:06,210 --> 00:14:10,470 You're seeing all these different kinds of traits 331 00:14:10,470 --> 00:14:12,750 and symptoms and you're thinking, you know, 332 00:14:12,750 --> 00:14:15,900 it could be related to maybe more of an aneuploidy 333 00:14:15,900 --> 00:14:19,950 or something in the environment or something like that 334 00:14:19,950 --> 00:14:22,830 as opposed to being the result of a single gene, 335 00:14:22,830 --> 00:14:24,480 one gene being mutated. 336 00:14:24,480 --> 00:14:26,100 However, that certainly can be the case 337 00:14:26,100 --> 00:14:28,653 and when that is the case, it's called pleiotropy. 338 00:14:29,850 --> 00:14:31,230 This indicates the protein encoded 339 00:14:31,230 --> 00:14:33,330 by this gene likely functions in different systems, 340 00:14:33,330 --> 00:14:35,190 as I said, and at different times, 341 00:14:35,190 --> 00:14:36,540 potentially in development. 342 00:14:37,440 --> 00:14:39,360 Genetic heterogeneity. 343 00:14:39,360 --> 00:14:42,330 One good example of genetic heterogeneity 344 00:14:42,330 --> 00:14:43,950 is polycystic kidney disease, 345 00:14:43,950 --> 00:14:46,340 which I'm showing you a picture of polycystic kidneys 346 00:14:46,340 --> 00:14:48,600 on the right-hand side here. 347 00:14:48,600 --> 00:14:51,543 And what that is is almost like the opposite of pleiotropy. 348 00:14:51,543 --> 00:14:54,450 So pleiotropy is mutations in one gene 349 00:14:54,450 --> 00:14:56,880 affecting multiple different phenotypes. 350 00:14:56,880 --> 00:14:59,010 This would be like seeing one phenotype, 351 00:14:59,010 --> 00:15:00,900 in this case, polycystic kidneys, 352 00:15:00,900 --> 00:15:02,910 and that could be caused by mutations 353 00:15:02,910 --> 00:15:04,740 in a number of different genes. 354 00:15:04,740 --> 00:15:07,590 Now, this is not polygenic. 355 00:15:07,590 --> 00:15:09,510 It does not mean that you need a mutation 356 00:15:09,510 --> 00:15:12,810 in each one of these genes to get polycystic kidney disease. 357 00:15:12,810 --> 00:15:13,920 It does not mean that. 358 00:15:13,920 --> 00:15:17,010 Genetic heterogeneity does mean that a mutation 359 00:15:17,010 --> 00:15:19,620 in any one of these genes here, 360 00:15:19,620 --> 00:15:23,490 in this case, for polycystic kidney disease, 361 00:15:23,490 --> 00:15:25,950 any one of these three genes and mutation in those, 362 00:15:25,950 --> 00:15:27,270 a disease mutation in those, 363 00:15:27,270 --> 00:15:29,610 would result in this condition. 364 00:15:29,610 --> 00:15:30,960 So you don't need mutations in all of them. 365 00:15:30,960 --> 00:15:35,430 It's just in any one of them could give you this disease. 366 00:15:35,430 --> 00:15:37,500 Now, what does that mean? 367 00:15:37,500 --> 00:15:40,760 Well, it could potentially impact 368 00:15:40,760 --> 00:15:42,900 when you're looking at what you would expect 369 00:15:42,900 --> 00:15:45,840 from Mendelian inheritance for genetic heterogeneity, 370 00:15:45,840 --> 00:15:47,970 you would expect to see, for example, 371 00:15:47,970 --> 00:15:52,260 if this is an autosomal recessive condition, let's say, 372 00:15:52,260 --> 00:15:57,260 and you have two parents that are both affected. 373 00:15:57,450 --> 00:15:59,370 When they have children, you expect all of their children 374 00:15:59,370 --> 00:16:01,020 to have polycystic kidney disease. 375 00:16:01,020 --> 00:16:03,690 However, that's not necessarily going to be the case 376 00:16:03,690 --> 00:16:05,910 if, say, one of the parents had a mutation 377 00:16:05,910 --> 00:16:10,910 in the PKD1 gene and the other parent had mutations, 378 00:16:11,010 --> 00:16:13,680 say, in the PKHD1 gene. 379 00:16:13,680 --> 00:16:17,540 So then their children would actually be heterozygous 380 00:16:17,540 --> 00:16:19,890 for mutations in each of those genes 381 00:16:19,890 --> 00:16:21,100 and could be perfectly normal 382 00:16:21,100 --> 00:16:23,680 if it's a recessive disease, 383 00:16:23,680 --> 00:16:27,120 all that is causing the disease. 384 00:16:27,120 --> 00:16:31,920 So I don't want to make this too confusing, 385 00:16:31,920 --> 00:16:33,570 but just wanted to give you a sense 386 00:16:33,570 --> 00:16:36,210 that it's not always so black and white. 387 00:16:36,210 --> 00:16:38,520 So again, one phenotype may be caused by mutations 388 00:16:38,520 --> 00:16:41,160 in any one of those different genes. 389 00:16:41,160 --> 00:16:43,440 And a patient with PKD could have a mutation 390 00:16:43,440 --> 00:16:45,660 in any one of those three genes 391 00:16:45,660 --> 00:16:47,703 with the same disease presentation. 392 00:16:48,660 --> 00:16:51,750 And you can also, it's important to keep in mind 393 00:16:51,750 --> 00:16:53,520 that disease mutations in these different genes 394 00:16:53,520 --> 00:16:55,530 may have different patterns of inheritance. 395 00:16:55,530 --> 00:16:56,760 In this case, they do. 396 00:16:56,760 --> 00:17:00,510 PKD1 and PKD2 mutations are dominantly inherited 397 00:17:00,510 --> 00:17:04,500 while PKHD1 mutations are recessively inherited. 398 00:17:04,500 --> 00:17:07,830 And often what is the molecular cause 399 00:17:07,830 --> 00:17:09,390 of having a mutation in any one 400 00:17:09,390 --> 00:17:11,680 of a number of different genes causing the same disease 401 00:17:11,680 --> 00:17:15,090 is that these genes code for proteins 402 00:17:15,090 --> 00:17:17,640 that are actually involved in the same pathway, 403 00:17:17,640 --> 00:17:20,010 same molecular pathway, play a role, 404 00:17:20,010 --> 00:17:21,220 maybe slightly different roles, 405 00:17:21,220 --> 00:17:24,300 but all sort of lead to the same effect. 406 00:17:24,300 --> 00:17:27,330 And so if you're interfering with any one of them, 407 00:17:27,330 --> 00:17:31,440 you could basically shut down the whole normal function 408 00:17:31,440 --> 00:17:32,853 and result in disease. 409 00:17:33,800 --> 00:17:37,200 All right, let's talk about penetrance and expressivity. 410 00:17:37,200 --> 00:17:39,720 So penetrance is the proportion of individuals 411 00:17:39,720 --> 00:17:42,210 with a mutation causing a particular disorder 412 00:17:42,210 --> 00:17:45,150 who exhibit clinical symptoms of that disorder. 413 00:17:45,150 --> 00:17:46,620 So let's think of it a different way. 414 00:17:46,620 --> 00:17:48,630 Percentage of the people who quote unquote 415 00:17:48,630 --> 00:17:50,720 should have a disease based on genotype 416 00:17:50,720 --> 00:17:53,160 that actually end up having it. 417 00:17:53,160 --> 00:17:54,540 So what do I mean by that? 418 00:17:54,540 --> 00:17:57,390 Well, sometimes with some diseases, 419 00:17:57,390 --> 00:17:59,720 you can have the genotype for the disease, 420 00:17:59,720 --> 00:18:04,720 but actually never develop the disease itself. 421 00:18:05,040 --> 00:18:07,140 So disease with reduced penetrance, 422 00:18:07,140 --> 00:18:09,480 it implies a patient with a genetic test result 423 00:18:09,480 --> 00:18:10,740 indicates they will have, 424 00:18:10,740 --> 00:18:12,660 or they have the genotype for the disease, 425 00:18:12,660 --> 00:18:17,040 but actually don't develop the disease ever necessarily. 426 00:18:17,040 --> 00:18:19,710 Some percentage of them may not ever develop it. 427 00:18:19,710 --> 00:18:23,220 A very common example of this is the BRCA1/2 mutations. 428 00:18:23,220 --> 00:18:25,980 And so these are related to breast cancer, 429 00:18:25,980 --> 00:18:29,010 increase the likelihood of developing breast cancer. 430 00:18:29,010 --> 00:18:30,693 So BRCA1/2 mutations, 431 00:18:31,600 --> 00:18:34,140 they're actually dominantly inherited. 432 00:18:34,140 --> 00:18:37,560 So if you inherit one copy from the mother or father, 433 00:18:37,560 --> 00:18:40,140 then that increases your, 434 00:18:40,140 --> 00:18:41,730 substantially increases your likelihood 435 00:18:41,730 --> 00:18:43,080 that you will develop breast cancer 436 00:18:43,080 --> 00:18:45,180 at some point in your lifetime. 437 00:18:45,180 --> 00:18:46,980 However, it does not guarantee it. 438 00:18:46,980 --> 00:18:48,720 So there are certainly some individuals 439 00:18:48,720 --> 00:18:50,580 who never develop breast cancer. 440 00:18:50,580 --> 00:18:52,890 And you can think for, in this case in particular, 441 00:18:52,890 --> 00:18:55,500 well, what are some possible reasons for that? 442 00:18:55,500 --> 00:18:57,900 Well, in the case of breast cancer, 443 00:18:57,900 --> 00:18:59,760 as you're probably very aware, 444 00:18:59,760 --> 00:19:01,920 that your likelihood of developing cancer 445 00:19:01,920 --> 00:19:05,610 is strongly linked to lifestyle choices, 446 00:19:05,610 --> 00:19:10,260 including diet and exercise, getting regular screenings. 447 00:19:10,260 --> 00:19:12,870 So these can reduce the chances 448 00:19:12,870 --> 00:19:14,820 of ever developing full-on breast cancer. 449 00:19:14,820 --> 00:19:17,340 Some diseases that have a, 450 00:19:17,340 --> 00:19:21,450 that are genetic diseases actually are not fully, 451 00:19:21,450 --> 00:19:23,520 what would be considered fully penetrant. 452 00:19:23,520 --> 00:19:25,737 They have reduced penetrance. 453 00:19:25,737 --> 00:19:27,930 And so there isn't necessarily a guarantee 454 00:19:27,930 --> 00:19:29,910 that the person will actually develop the disease, 455 00:19:29,910 --> 00:19:31,953 even if they have the genotype for it. 456 00:19:32,840 --> 00:19:36,450 So expressivity, what does expressivity mean? 457 00:19:36,450 --> 00:19:40,950 Well, that means the extent to which you have symptoms 458 00:19:40,950 --> 00:19:44,070 or the phenotype of a disease might vary. 459 00:19:44,070 --> 00:19:45,570 So variation in the extent to 460 00:19:45,570 --> 00:19:47,310 which a phenotype is expressed. 461 00:19:47,310 --> 00:19:49,260 So this would be the extent to which an individual 462 00:19:49,260 --> 00:19:52,080 who has a genetic disease expresses the symptoms, 463 00:19:52,080 --> 00:19:55,080 mild, moderate, severe, and also the stage of onset, 464 00:19:55,080 --> 00:19:57,300 whether it's early onset or late onset. 465 00:19:57,300 --> 00:19:59,010 So variable expressivity is just 466 00:19:59,010 --> 00:20:00,300 how a disease will play out. 467 00:20:00,300 --> 00:20:02,960 A person does have the disease. 468 00:20:02,960 --> 00:20:06,330 And so let's contrast this with penetrance 469 00:20:06,330 --> 00:20:08,910 because oftentimes these two get confused, 470 00:20:08,910 --> 00:20:09,870 these two concepts. 471 00:20:09,870 --> 00:20:13,230 Penetrance is do you have the disease, yes or no, right? 472 00:20:13,230 --> 00:20:15,180 Penetrance is a yes, no question. 473 00:20:15,180 --> 00:20:18,390 If you, in diseases that have reduced penetrance, 474 00:20:18,390 --> 00:20:21,330 there's a certain percentage of the population of people 475 00:20:21,330 --> 00:20:24,000 who have the genotype who no, 476 00:20:24,000 --> 00:20:25,830 do not ever develop the disease. 477 00:20:25,830 --> 00:20:29,820 So that's sort of the yes, no question. 478 00:20:29,820 --> 00:20:32,990 Expressivity is the extent to which you have a disease. 479 00:20:32,990 --> 00:20:34,470 Do you have a bad case of it, 480 00:20:34,470 --> 00:20:37,340 or sort of a less severe case of it? 481 00:20:37,340 --> 00:20:39,600 Do you develop it early in life, later in life? 482 00:20:39,600 --> 00:20:41,100 It's sort of how the disease plays out, 483 00:20:41,100 --> 00:20:43,120 but you do have the disease. 484 00:20:43,120 --> 00:20:45,600 All right, so disease with variable expressivity 485 00:20:45,600 --> 00:20:47,160 implies patients with the disease 486 00:20:47,160 --> 00:20:49,170 have variable degrees of symptoms, 487 00:20:49,170 --> 00:20:50,730 severity, and presentation. 488 00:20:50,730 --> 00:20:52,350 Example is shown here on the right. 489 00:20:52,350 --> 00:20:54,660 Patients with neurofibromatosis, 490 00:20:54,660 --> 00:20:58,740 an NF1 mutation will develop neurofibromatosis, they will, 491 00:20:58,740 --> 00:21:02,610 but some will have mild freckling or cafe au lait spots, 492 00:21:02,610 --> 00:21:04,560 as you can see here in this top picture, 493 00:21:04,560 --> 00:21:08,610 and others will have life-threatening CNS tumors 494 00:21:08,610 --> 00:21:10,830 and tumors all over the body, 495 00:21:10,830 --> 00:21:13,230 as you can see in this picture on the bottom here. 496 00:21:13,230 --> 00:21:15,420 So both of these individuals 497 00:21:15,420 --> 00:21:19,830 have potentially the same mutation in the NF1 gene 498 00:21:19,830 --> 00:21:21,750 that would result in neurofibromatosis, 499 00:21:21,750 --> 00:21:23,190 but it plays out very differently 500 00:21:23,190 --> 00:21:25,320 from one person to the next. 501 00:21:25,320 --> 00:21:27,210 Remember, penetrance is the percentage of people 502 00:21:27,210 --> 00:21:29,430 who actually end up developing the disease. 503 00:21:29,430 --> 00:21:31,140 You have the genotype for it. 504 00:21:31,140 --> 00:21:34,890 Expressivity is the degree or the extent 505 00:21:34,890 --> 00:21:38,130 to which that disease is more or less severe, 506 00:21:38,130 --> 00:21:40,680 earlier or late onset, how the disease plays out, 507 00:21:40,680 --> 00:21:44,100 but a person does have the disease with expressivity. 508 00:21:44,100 --> 00:21:45,660 So what causes incomplete penetrance 509 00:21:45,660 --> 00:21:47,310 and variable expressivity? 510 00:21:47,310 --> 00:21:51,930 Well, one reason is another concept called epistasis. 511 00:21:51,930 --> 00:21:54,680 Epistasis is the effect of one gene's alleles 512 00:21:54,680 --> 00:21:56,760 on another gene's alleles. 513 00:21:56,760 --> 00:21:59,700 So this basically means we're not all, 514 00:21:59,700 --> 00:22:01,590 they're not just a combination of single genes 515 00:22:01,590 --> 00:22:03,720 and they all perform one single function. 516 00:22:03,720 --> 00:22:07,290 No, no, no, it's a community going on inside of your cells, 517 00:22:07,290 --> 00:22:09,870 and epistasis is quite common, 518 00:22:09,870 --> 00:22:12,783 which basically means your genetic background. 519 00:22:13,800 --> 00:22:15,330 Other genes that you, you know, 520 00:22:15,330 --> 00:22:17,340 other mutations that you might have might be, 521 00:22:17,340 --> 00:22:18,900 and other genes might be affecting 522 00:22:18,900 --> 00:22:21,570 the way a particular disease mutation 523 00:22:21,570 --> 00:22:23,673 that you've inherited is playing out. 524 00:22:24,630 --> 00:22:27,000 It could also be influenced by the environment. 525 00:22:27,000 --> 00:22:29,490 So this would include nutrition, stress, 526 00:22:29,490 --> 00:22:32,200 any comorbidities you have, general health and wellbeing. 527 00:22:32,200 --> 00:22:34,380 As you all know very, very well 528 00:22:34,380 --> 00:22:35,790 that you see in your patients, 529 00:22:35,790 --> 00:22:37,170 you can have two patients that are diagnosed 530 00:22:37,170 --> 00:22:38,640 with the exact same disease 531 00:22:38,640 --> 00:22:40,560 and it plays out quite differently. 532 00:22:40,560 --> 00:22:42,330 And many times a lot of that has to do 533 00:22:42,330 --> 00:22:45,510 with just how healthy a person is more generally. 534 00:22:45,510 --> 00:22:47,820 How well do they take care of themselves? 535 00:22:47,820 --> 00:22:48,990 What's their nutrition like? 536 00:22:48,990 --> 00:22:50,070 What's their level of stress? 537 00:22:50,070 --> 00:22:51,840 What other diseases do they have? 538 00:22:51,840 --> 00:22:53,400 And sometimes a disease was present 539 00:22:53,400 --> 00:22:55,470 but not diagnosed in a family member. 540 00:22:55,470 --> 00:22:57,450 So when you're actually taking the family history 541 00:22:57,450 --> 00:22:58,283 and looking at a pedigree, 542 00:22:58,283 --> 00:23:00,270 it appears to be incomplete penetrance, 543 00:23:00,270 --> 00:23:02,040 but actually it might not be. 544 00:23:02,040 --> 00:23:06,780 It may just be that either someone passed away 545 00:23:06,780 --> 00:23:09,330 before a disease would have presented itself. 546 00:23:09,330 --> 00:23:12,360 So that's something that you might see. 547 00:23:12,360 --> 00:23:13,560 Someone might say, well, 548 00:23:15,800 --> 00:23:18,630 my grandfather had this dominant disease, 549 00:23:18,630 --> 00:23:20,220 had Huntington's disease, 550 00:23:20,220 --> 00:23:23,820 and then my dad didn't have it, so I'm okay. 551 00:23:23,820 --> 00:23:25,740 Well, maybe or maybe not. 552 00:23:25,740 --> 00:23:27,780 If say the father died, 553 00:23:27,780 --> 00:23:29,250 if that person's father died 554 00:23:29,250 --> 00:23:31,180 before he would have started presenting 555 00:23:31,180 --> 00:23:33,900 with Huntington's disease symptoms, 556 00:23:33,900 --> 00:23:36,450 it may appear to be incomplete penetrance, 557 00:23:36,450 --> 00:23:38,820 but really it was just never diagnosed 558 00:23:38,820 --> 00:23:40,380 because the person didn't live long enough 559 00:23:40,380 --> 00:23:43,770 to have the disease express itself. 560 00:23:43,770 --> 00:23:47,010 And similarly, it could just be that in some people, 561 00:23:47,010 --> 00:23:48,420 they were just never diagnosed 562 00:23:48,420 --> 00:23:50,190 and lived with a disease 563 00:23:50,190 --> 00:23:52,233 or had a more mild form of a disease. 564 00:23:53,520 --> 00:23:55,260 All right, so what are some of the implications? 565 00:23:55,260 --> 00:23:56,670 Not all single gene diseases 566 00:23:56,670 --> 00:23:58,500 will demonstrate the expected pattern 567 00:23:58,500 --> 00:24:01,170 of inheritance based on phenotype 568 00:24:01,170 --> 00:24:02,460 and be prepared to interpret 569 00:24:02,460 --> 00:24:04,410 seemingly contradictory information 570 00:24:04,410 --> 00:24:07,020 through those principles of types of dominance, 571 00:24:07,020 --> 00:24:09,690 pleiotropy, genetic heterogeneity, 572 00:24:09,690 --> 00:24:12,180 penetrance, and expressivity. 573 00:24:12,180 --> 00:24:14,070 All right, so let's take a quick summary here. 574 00:24:14,070 --> 00:24:16,530 Some alleles are not fully dominant to other alleles, 575 00:24:16,530 --> 00:24:19,440 leading children to have a mixed phenotype. 576 00:24:19,440 --> 00:24:21,720 So whether that's the blended phenotype 577 00:24:21,720 --> 00:24:23,000 of incomplete dominance 578 00:24:23,000 --> 00:24:26,820 or the sort of patchwork phenotype, 579 00:24:26,820 --> 00:24:29,760 you can think of it as codominance. 580 00:24:29,760 --> 00:24:31,620 One disease mutation in a single gene 581 00:24:31,620 --> 00:24:33,930 can sometimes result in different traits 582 00:24:33,930 --> 00:24:35,850 or phenotypes, this is pleiotropy, 583 00:24:35,850 --> 00:24:37,830 and mutations in different genes 584 00:24:37,830 --> 00:24:39,810 can sometimes result in the same trait. 585 00:24:39,810 --> 00:24:41,190 And this is genetic heterogeneity, 586 00:24:41,190 --> 00:24:44,100 sort of like the other side of the coin of pleiotropy. 587 00:24:44,100 --> 00:24:46,920 Phenotypes may vary in presentation and severity 588 00:24:46,920 --> 00:24:49,290 due to variable expressivity. 589 00:24:49,290 --> 00:24:51,060 Remember that variable expressivity 590 00:24:51,060 --> 00:24:54,840 is really the extent to which a disease, 591 00:24:54,840 --> 00:24:56,400 how a disease plays out, basically. 592 00:24:56,400 --> 00:24:58,620 A person has a disease and how it plays out 593 00:24:58,620 --> 00:25:01,110 is variable expressivity. 594 00:25:01,110 --> 00:25:03,120 Phenotypes may appear to skip presenting 595 00:25:03,120 --> 00:25:05,820 in some individuals due to incomplete penetrance. 596 00:25:05,820 --> 00:25:10,770 Incomplete penetrance means the percentage of individuals 597 00:25:10,770 --> 00:25:12,750 who do not develop the disease 598 00:25:12,750 --> 00:25:16,260 but do have the genotype for it. 599 00:25:16,260 --> 00:25:18,930 Okay, so I think that's a pretty good list 600 00:25:18,930 --> 00:25:23,930 of some exceptions that are important to stay aware of. 601 00:25:24,300 --> 00:25:28,640 And so that wraps up this fifth module. 602 00:25:28,640 --> 00:25:31,230 And what we're going to move on to 603 00:25:31,230 --> 00:25:34,380 is some traits of non-Mendelian inheritance. 604 00:25:34,380 --> 00:25:36,030 And here we're also going to start talking 605 00:25:36,030 --> 00:25:38,820 about multifactorial genetic disease. 606 00:25:38,820 --> 00:25:41,070 And so it gets a little bit more complicated 607 00:25:41,070 --> 00:25:43,230 with actually a multifactorial genetic disease. 608 00:25:43,230 --> 00:25:47,580 These are like what we would consider everyday conditions 609 00:25:47,580 --> 00:25:50,670 of heart disease, diabetes, cancer. 610 00:25:50,670 --> 00:25:54,030 Many of these are multifactorial genetic diseases 611 00:25:54,030 --> 00:25:56,670 and they're incredibly important 612 00:25:56,670 --> 00:25:58,120 for us to better understand. 613 00:25:58,120 --> 00:26:00,480 So that's gonna be what's up next. 614 00:26:00,480 --> 00:26:02,910 In the next module, 615 00:26:02,910 --> 00:26:06,420 that's going to be in the next new material module. 616 00:26:06,420 --> 00:26:09,600 I am going to give you in module six, 617 00:26:09,600 --> 00:26:12,390 what we're going to do in the next week after this 618 00:26:12,390 --> 00:26:14,220 is we're going to take a beat 619 00:26:14,220 --> 00:26:17,280 and just absorb everything that you've learned, 620 00:26:17,280 --> 00:26:18,180 not just in this module 621 00:26:18,180 --> 00:26:20,340 but all the previous modules up until now. 622 00:26:20,340 --> 00:26:22,530 It's a tremendous amount of material 623 00:26:22,530 --> 00:26:24,300 and you're doing fantastic with it. 624 00:26:24,300 --> 00:26:26,850 And I just want to make sure we take a moment 625 00:26:26,850 --> 00:26:31,850 to absorb it all and make sure that it's all registering. 626 00:26:32,100 --> 00:26:34,440 You'll have a chance to do your midterm exam 627 00:26:34,440 --> 00:26:36,720 which will be based upon these first five modules 628 00:26:36,720 --> 00:26:39,090 that you've learned as the foundation 629 00:26:39,090 --> 00:26:41,550 for what we're gonna do in the second half of the course. 630 00:26:41,550 --> 00:26:44,850 Yeah, with that, I will say goodbye 631 00:26:44,850 --> 00:26:48,243 and I look forward to talking with you soon.