1 00:00:02,880 --> 00:00:05,343 [Wildin] Hello, this is Dr. Bob Wildin. 2 00:00:06,210 --> 00:00:11,210 Welcome to Module 6, Lecture 3 in Pedigree Part 2. 3 00:00:14,940 --> 00:00:19,940 This part of the module talks about 4 00:00:21,390 --> 00:00:26,390 some unusual, but not at all uncommon these days, 5 00:00:26,573 --> 00:00:31,050 variations in pedigree nomenclature 6 00:00:31,050 --> 00:00:35,260 that are necessary for us to correctly represent 7 00:00:36,201 --> 00:00:40,833 the types of patients that we see in our clinics today. 8 00:00:42,600 --> 00:00:46,193 I did want to start out with a review 9 00:00:49,080 --> 00:00:52,740 of penetrance and expressivity, 10 00:00:52,740 --> 00:00:57,740 which you will have experienced in Tamara Williams' lecture 11 00:00:59,220 --> 00:01:01,023 earlier in this module. 12 00:01:03,150 --> 00:01:08,150 Penetrance, the concept is if you have full penetrance, 13 00:01:08,250 --> 00:01:13,250 is what you think of when you say a gene causes a disease. 14 00:01:13,800 --> 00:01:16,350 Full penetrance is if you have the gene, 15 00:01:16,350 --> 00:01:18,180 you will get the disease. 16 00:01:18,180 --> 00:01:22,320 No getting around it, no reduced risk, 17 00:01:22,320 --> 00:01:24,810 no increased risk question about it. 18 00:01:24,810 --> 00:01:26,883 Eventually you'll get that disease. 19 00:01:27,720 --> 00:01:32,160 Reduced penetrance means that you have less than 100% chance 20 00:01:32,160 --> 00:01:35,220 of getting the disease, even if you have inherited 21 00:01:35,220 --> 00:01:36,627 the disease gene (allele). 22 00:01:38,310 --> 00:01:41,335 So what that means is when you're counseling families 23 00:01:41,335 --> 00:01:45,540 who are studying the inheritance 24 00:01:45,540 --> 00:01:49,710 of a particular disease in their family, 25 00:01:49,710 --> 00:01:54,710 if that condition has reduced penetrance observed, 26 00:01:56,010 --> 00:02:00,690 then that means that the message 27 00:02:00,690 --> 00:02:04,950 to the person who was inherited that gene change 28 00:02:04,950 --> 00:02:09,950 but hasn't grown old enough, say, to express the disease, 29 00:02:10,500 --> 00:02:13,710 is that you have an increased risk. 30 00:02:13,710 --> 00:02:16,920 And sometimes we can put a number on that. 31 00:02:16,920 --> 00:02:21,280 For example, with BRCA1, the risk of having breast cancer 32 00:02:21,280 --> 00:02:25,740 in your lifetime is approximately 80%. 33 00:02:25,740 --> 00:02:27,150 So it has reduced penetrance, 34 00:02:27,150 --> 00:02:30,483 but it's still pretty high penetrance, all right? 35 00:02:31,860 --> 00:02:33,960 Low penetrance means 36 00:02:33,960 --> 00:02:37,140 many people who inherit the disease allele 37 00:02:37,140 --> 00:02:40,578 or the disease alleles, depending on the type of 38 00:02:40,578 --> 00:02:43,200 inheritance you're talking about, 39 00:02:43,200 --> 00:02:45,800 will not be affected by the disease, 40 00:02:45,800 --> 00:02:49,375 but the risk of getting the disease is still much higher 41 00:02:49,375 --> 00:02:52,410 than if you hadn't inherited the disease genotype. 42 00:02:52,410 --> 00:02:54,300 Now what does that mean? 43 00:02:54,300 --> 00:02:59,300 In the case of rare diseases, the chance that someone who 44 00:03:00,411 --> 00:03:03,240 doesn't have a disease gene running in the family 45 00:03:03,240 --> 00:03:06,963 will get it, is very, very, very, very small. 46 00:03:08,700 --> 00:03:10,620 When we talk about low penetrance, 47 00:03:10,620 --> 00:03:15,620 we're saying something like individuals who have inherited 48 00:03:16,140 --> 00:03:19,935 the genetic makeup that you would ordinarily think 49 00:03:19,935 --> 00:03:23,640 would cause the disease have perhaps 50 00:03:23,640 --> 00:03:28,640 a 20, 30, 40, 50% chance of expressing that disease. 51 00:03:32,460 --> 00:03:36,690 That's still a whole lot higher than if they didn't have 52 00:03:36,690 --> 00:03:39,483 a disease gene set running in the family. 53 00:03:41,340 --> 00:03:45,036 The other important point is even people who 54 00:03:45,036 --> 00:03:49,510 don't express the disease due to decreased penetrance 55 00:03:50,670 --> 00:03:55,080 will still have the same risks of passing on that gene 56 00:03:55,080 --> 00:03:57,780 to their children, right? 57 00:03:57,780 --> 00:04:01,740 So the Mendelian inheritance patterns and frequencies 58 00:04:01,740 --> 00:04:06,740 of passing on are not connected to reduced penetrance. 59 00:04:09,990 --> 00:04:11,430 If you have questions about that, 60 00:04:11,430 --> 00:04:13,683 let's talk about it on the discussion board. 61 00:04:17,040 --> 00:04:21,900 So the next term, which is frequently 62 00:04:21,900 --> 00:04:24,993 confused with penetrance is expressivity. 63 00:04:25,950 --> 00:04:28,170 So penetrance, we're really talking about the fraction 64 00:04:28,170 --> 00:04:31,980 of people who are at risk who will get the disease 65 00:04:31,980 --> 00:04:33,630 With expressivity, 66 00:04:33,630 --> 00:04:38,220 we're not talking about the fraction of individuals, 67 00:04:38,220 --> 00:04:39,370 we're talking about 68 00:04:40,230 --> 00:04:43,781 which specific manifestations of the disease 69 00:04:43,781 --> 00:04:48,603 will a person who does manifest it express. 70 00:04:49,980 --> 00:04:54,450 So a uniform expressivity means that the disease, 71 00:04:54,450 --> 00:04:56,550 everybody who has this disease 72 00:04:56,550 --> 00:04:59,853 will pretty much have the same clinical manifestations. 73 00:05:00,990 --> 00:05:04,530 Whereas variable expressivity means 74 00:05:04,530 --> 00:05:08,730 some people who have this disease will be more severe 75 00:05:08,730 --> 00:05:13,560 or have different subset of features than others, 76 00:05:13,560 --> 00:05:17,163 even if they inherit exactly the same genetic variant. 77 00:05:18,090 --> 00:05:22,683 So one example is neurofibromatosis type 1, 78 00:05:23,669 --> 00:05:28,669 which is a complex disorder that causes learning disability, 79 00:05:33,695 --> 00:05:38,500 cutaneous and subcutaneous tumors that are 80 00:05:39,691 --> 00:05:44,691 benign tumors of the nerve sheath, more advanced tumors, 81 00:05:46,920 --> 00:05:49,500 they may also have short stature, 82 00:05:49,500 --> 00:05:51,993 they may have facial differences, 83 00:05:52,920 --> 00:05:55,560 and a variety of other features. 84 00:05:55,560 --> 00:05:56,670 I'm leaving out the one 85 00:05:56,670 --> 00:05:59,730 that is most prominent and most common 86 00:05:59,730 --> 00:06:04,173 is multiple cafe au lait maculas on the skin. 87 00:06:05,760 --> 00:06:07,050 So-called birthmarks, 88 00:06:07,050 --> 00:06:09,960 although they often appear in the first few years of life 89 00:06:09,960 --> 00:06:11,733 instead of being present at birth. 90 00:06:13,230 --> 00:06:16,740 So variable penetrance in the case of neurofibromatosis 91 00:06:16,740 --> 00:06:21,740 means that some people may have a very severe case, 92 00:06:21,780 --> 00:06:26,780 whereas others may have cafe au lait spots, 93 00:06:26,850 --> 00:06:29,130 what's called Crowe sign, which is freckles 94 00:06:29,130 --> 00:06:30,993 in the armpits in the groins, 95 00:06:31,903 --> 00:06:36,903 and maybe a few cutaneous or subcutaneous neurofibromas, 96 00:06:39,840 --> 00:06:42,330 which don't cause much problem, 97 00:06:42,330 --> 00:06:45,693 and they may not have any significant learning disability. 98 00:06:47,130 --> 00:06:50,700 Whereas others may have a really severe case. 99 00:06:50,700 --> 00:06:55,203 So that's an example of variable expressivity. 100 00:06:56,700 --> 00:07:00,339 Now, what are the origins of decreased penetrance 101 00:07:00,339 --> 00:07:02,711 and variable expressivity? 102 00:07:02,711 --> 00:07:06,570 Some of it has to do with environmental exposures. 103 00:07:06,570 --> 00:07:09,270 Some of it may have to do with somatic mutations 104 00:07:09,270 --> 00:07:11,550 and the frequency of somatic mutations. 105 00:07:11,550 --> 00:07:16,550 A lot of the tumor manifestations in neurofibromatosis 106 00:07:16,770 --> 00:07:20,550 are due to somatic mutations that occur 107 00:07:20,550 --> 00:07:23,472 potentially at different frequencies depending on exposures, 108 00:07:23,472 --> 00:07:27,180 environmental differences, and fundamental differences 109 00:07:27,180 --> 00:07:29,193 in genetic stability. 110 00:07:31,500 --> 00:07:34,200 In conditions with decreased penetrance 111 00:07:34,200 --> 00:07:35,850 and variable expressivity, 112 00:07:35,850 --> 00:07:37,860 there's a lot of new research going on 113 00:07:37,860 --> 00:07:40,950 talking about the genetic landscape. 114 00:07:40,950 --> 00:07:43,530 And what is meant by genetic landscape? 115 00:07:43,530 --> 00:07:45,930 It took me a while to figure this out. 116 00:07:45,930 --> 00:07:49,890 And what people mean is that there are, 117 00:07:49,890 --> 00:07:52,680 in addition to the specific genetic change 118 00:07:52,680 --> 00:07:57,030 associated with the disease in a particular gene, 119 00:07:57,030 --> 00:08:01,500 there's a wide variety of other variations in the genome, 120 00:08:01,500 --> 00:08:06,243 a few of which may influence penetrance and expressivity. 121 00:08:07,200 --> 00:08:12,200 So when you hear about learning about the genetic landscape 122 00:08:12,270 --> 00:08:16,050 of a particular disease, what they're learning about is 123 00:08:16,050 --> 00:08:21,050 other genetic variations that underlie 124 00:08:21,090 --> 00:08:23,703 the concepts of penetrance and expressivity. 125 00:08:24,750 --> 00:08:29,010 All right, so I'm gonna move on from that concept, 126 00:08:29,010 --> 00:08:32,070 but I wanted to cover it again because it's 127 00:08:32,070 --> 00:08:36,270 an extremely important concept and frequently is confusing 128 00:08:36,270 --> 00:08:38,493 both to providers and patients. 129 00:08:39,983 --> 00:08:44,983 So last week we talked about the pedigree language 130 00:08:45,690 --> 00:08:49,680 and I showed this slide where there are specific symbols 131 00:08:49,680 --> 00:08:54,680 for persons depending on their gender and their number. 132 00:08:58,241 --> 00:09:02,970 There are specific symbols for status, 133 00:09:02,970 --> 00:09:06,240 including alive and deceased, affected with the condition, 134 00:09:06,240 --> 00:09:10,773 unaffected, carrier, and being adopted. 135 00:09:12,000 --> 00:09:16,440 And this concept of the horizontal and vertical lines 136 00:09:16,440 --> 00:09:21,206 that represent the relationships, 137 00:09:21,206 --> 00:09:25,020 the different kinds of relationships within a family. 138 00:09:25,020 --> 00:09:29,040 So the vertical line, I call a generational relationship. 139 00:09:29,040 --> 00:09:33,931 Solid line means there is a genetic relationship 140 00:09:33,931 --> 00:09:36,724 and a dash line means there's a non-genetic, 141 00:09:36,724 --> 00:09:41,163 perhaps a social relationship, like I have adopted you. 142 00:09:42,612 --> 00:09:47,310 In the horizontal line category, 143 00:09:47,310 --> 00:09:49,980 there are really two types of horizontal lines 144 00:09:49,980 --> 00:09:54,980 that which links partners in a parental-style relationship, 145 00:09:58,860 --> 00:10:02,133 in a couple, whether or not they mate. 146 00:10:03,810 --> 00:10:07,350 And a sibship horizontal line, 147 00:10:07,350 --> 00:10:09,500 which is shown at the bottom of this slide. 148 00:10:11,430 --> 00:10:13,410 Okay, so that's kind of review 149 00:10:13,410 --> 00:10:18,410 and I did also have a dotted line for casual relationships 150 00:10:18,501 --> 00:10:22,890 or relationships that are no longer active. 151 00:10:22,890 --> 00:10:26,343 For example, divorced couples. 152 00:10:28,380 --> 00:10:31,770 All right, so this is from Robin Bennett, 153 00:10:31,770 --> 00:10:34,930 who's a genetic counselor 154 00:10:36,150 --> 00:10:39,720 who really defined and standardized 155 00:10:39,720 --> 00:10:44,720 the way that we use pedigree symbols. 156 00:10:45,180 --> 00:10:48,660 And this is her definition. 157 00:10:48,660 --> 00:10:50,820 That the horizontal line between partners 158 00:10:50,820 --> 00:10:53,040 is a relationship line. 159 00:10:53,040 --> 00:10:54,420 There's the sibship line, 160 00:10:54,420 --> 00:10:56,868 the horizontal line between siblings, 161 00:10:56,868 --> 00:11:01,050 the individual's line within the sibship, 162 00:11:01,050 --> 00:11:03,150 and then the line of descent 163 00:11:03,150 --> 00:11:05,553 is the vertical line from the partnership. 164 00:11:09,676 --> 00:11:12,750 Adoption, just to go over again, 165 00:11:12,750 --> 00:11:17,065 is represented as a closed brackets, 166 00:11:17,065 --> 00:11:20,370 square brackets that face each other 167 00:11:20,370 --> 00:11:23,973 around the individual who was adopted. 168 00:11:25,200 --> 00:11:30,030 It's important to note that the couple that adopts them, 169 00:11:30,030 --> 00:11:34,080 or the individual that adopts the person who's adopted 170 00:11:34,080 --> 00:11:36,270 does not have a genetic relationship, 171 00:11:36,270 --> 00:11:41,270 a direct genetic relationship with the adopted person, 172 00:11:41,430 --> 00:11:43,480 although it may be another family member. 173 00:11:44,460 --> 00:11:49,353 And so that's represented by a dashed line. 174 00:11:50,520 --> 00:11:55,520 If there is the a solid line, 175 00:11:55,950 --> 00:11:59,820 a vertical or off-vertical, at-an-angle line 176 00:11:59,820 --> 00:12:03,880 can also be present in order to represent 177 00:12:05,220 --> 00:12:09,420 the genetic relationship to the family of origin, 178 00:12:09,420 --> 00:12:10,533 the birth family. 179 00:12:13,020 --> 00:12:15,570 And we'll go through some examples of that. 180 00:12:15,570 --> 00:12:17,370 So the other thing about this slide that you'll notice 181 00:12:17,370 --> 00:12:19,350 if you're watching carefully 182 00:12:19,350 --> 00:12:24,350 is that the parent couples are same-sex couples. 183 00:12:24,960 --> 00:12:29,874 So this is the way that you represent same-sex couples 184 00:12:29,874 --> 00:12:34,863 when there's an adopted child in the family. 185 00:12:36,450 --> 00:12:39,210 I will say that I know a lot of same-sex couples 186 00:12:39,210 --> 00:12:42,490 where one, or the other, or both 187 00:12:43,350 --> 00:12:47,190 have been married in heterosexual partnerships previously 188 00:12:47,190 --> 00:12:50,607 and have genetic children and those would be represented 189 00:12:50,607 --> 00:12:54,243 in the usual solid, vertical line fashion. 190 00:12:56,130 --> 00:13:00,510 But in the relationship line of the male-female partnership, 191 00:13:00,510 --> 00:13:04,023 which was the meeting partners. 192 00:13:05,760 --> 00:13:10,743 Okay, so let's look at pedigree a language advanced. 193 00:13:15,420 --> 00:13:18,813 The first panel shows more person symbols. 194 00:13:19,800 --> 00:13:24,330 A diamond with a P in it represents a pregnancy. 195 00:13:24,330 --> 00:13:27,176 Oftentimes, you'll see the diamond be small 196 00:13:27,176 --> 00:13:29,824 in the case of a pregnancy. 197 00:13:29,824 --> 00:13:32,700 If you have done sexing on the pregnancy, 198 00:13:32,700 --> 00:13:33,900 you know the sex of the pregnancy, 199 00:13:33,900 --> 00:13:35,940 you can turn it sideways or round it out 200 00:13:35,940 --> 00:13:37,680 and make it a male or a female. 201 00:13:37,680 --> 00:13:40,380 But keep the little P inside of it to represent 202 00:13:40,380 --> 00:13:44,523 it's still a fetus in the womb. 203 00:13:46,292 --> 00:13:51,292 If a person is an egg donor, you put a D inside a circle 204 00:13:53,160 --> 00:13:55,803 because women donate eggs. 205 00:13:56,670 --> 00:13:58,208 Female. 206 00:13:58,208 --> 00:14:00,210 To be more precise, 207 00:14:00,210 --> 00:14:03,430 those with the ability, ovaries to create eggs 208 00:14:06,946 --> 00:14:09,603 are the only ones who can donate them. 209 00:14:10,800 --> 00:14:14,280 Similarly, those who have the ability to produce sperm 210 00:14:14,280 --> 00:14:16,140 are the only ones who donate them, 211 00:14:16,140 --> 00:14:20,493 so they're represented by a square with a D in the middle. 212 00:14:22,680 --> 00:14:26,920 A surrogate is an individual who carries a pregnancy 213 00:14:31,290 --> 00:14:32,943 with an implanted embryo. 214 00:14:34,140 --> 00:14:37,413 And occasionally, the surrogate can also be, 215 00:14:38,280 --> 00:14:40,860 essentially, the donor of the egg, 216 00:14:40,860 --> 00:14:42,480 so you have to take that into account too. 217 00:14:42,480 --> 00:14:44,763 But the S in the middle represents surrogate. 218 00:14:46,620 --> 00:14:49,470 Transgender individuals are represented 219 00:14:49,470 --> 00:14:52,349 by their identification, 220 00:14:52,349 --> 00:14:55,593 the gender symbol with which they identify. 221 00:14:56,760 --> 00:15:01,760 And so a person who was assigned a traditional gender 222 00:15:04,080 --> 00:15:08,700 of female at birth and transitioned to male 223 00:15:08,700 --> 00:15:13,700 has a male symbol with the annotation of FTM 224 00:15:14,190 --> 00:15:16,860 standing for female to male above 225 00:15:16,860 --> 00:15:20,433 or just over to the side and above that symbol. 226 00:15:22,290 --> 00:15:27,280 Likewise, a male to female transgender person 227 00:15:27,280 --> 00:15:32,280 is represented as a female with MTF for male to female 228 00:15:34,380 --> 00:15:37,443 annotated above or above and to the side. 229 00:15:39,000 --> 00:15:43,270 So those are new symbols 230 00:15:44,953 --> 00:15:48,813 but actually come in handy fairly often these days. 231 00:15:50,280 --> 00:15:52,440 I wanted to make the point in the next panel 232 00:15:52,440 --> 00:15:55,560 about this vertical generational relationship. 233 00:15:55,560 --> 00:16:00,560 And it doesn't always have to be drawn absolutely vertical. 234 00:16:02,570 --> 00:16:05,130 Sometimes there are places 235 00:16:05,130 --> 00:16:08,610 where we need to make it vertical-ish. 236 00:16:08,610 --> 00:16:11,910 So if the line is mostly vertical, 237 00:16:11,910 --> 00:16:14,943 it still represents that generational relationship. 238 00:16:16,890 --> 00:16:21,321 Has a new twist that we didn't talk about last year, 239 00:16:21,321 --> 00:16:25,830 which is a horizontal line between the partners 240 00:16:25,830 --> 00:16:27,033 that is doubled. 241 00:16:28,470 --> 00:16:31,700 And a double line represents... 242 00:16:33,660 --> 00:16:35,430 I've got some extra animations in here. 243 00:16:35,430 --> 00:16:37,830 Sorry, there's a line. (laughs) 244 00:16:37,830 --> 00:16:42,830 So a double partnership line means there is consanguinity. 245 00:16:43,260 --> 00:16:44,640 What does that mean? 246 00:16:44,640 --> 00:16:49,113 Consequently literally means they contain the same blood. 247 00:16:50,940 --> 00:16:52,170 From a genetic standpoint, 248 00:16:52,170 --> 00:16:55,443 it means that they had a common ancestor. 249 00:16:56,730 --> 00:16:59,640 So if you take their family history and keep going 250 00:16:59,640 --> 00:17:01,773 back and back and back, eventually, 251 00:17:03,731 --> 00:17:07,350 there will be an individual who was in 252 00:17:07,350 --> 00:17:10,660 their great-great-grandmother, grandfather lineage 253 00:17:11,580 --> 00:17:14,913 for both the male and the female partner. 254 00:17:16,873 --> 00:17:19,920 This can happen in the same generation, 255 00:17:19,920 --> 00:17:22,470 it can happen across generations. 256 00:17:22,470 --> 00:17:25,233 It can happen in a lot of different ways. 257 00:17:26,070 --> 00:17:28,440 And the reason that we put that in there 258 00:17:28,440 --> 00:17:31,500 is because some degree of consanguinity, 259 00:17:31,500 --> 00:17:34,110 particularly if the common ancestor 260 00:17:34,110 --> 00:17:37,408 is fairly recent in the family, 261 00:17:37,408 --> 00:17:42,408 increases your risk of recessive disorders in the children 262 00:17:44,400 --> 00:17:48,180 because there are more segments of the genome, 263 00:17:48,180 --> 00:17:52,470 which are identical by dissent or shared 264 00:17:52,470 --> 00:17:56,580 between these two individuals and if any of those contains 265 00:17:56,580 --> 00:18:01,580 a recessive gene allele, it could be passed on 266 00:18:02,460 --> 00:18:06,750 from both parents with reasonably high frequency. 267 00:18:06,750 --> 00:18:09,630 So a double line means consanguinity. 268 00:18:09,630 --> 00:18:12,120 There's a little flag for potentially 269 00:18:12,120 --> 00:18:15,390 an increased risk for recessive disorder, 270 00:18:15,390 --> 00:18:20,390 unless that common ancestor relationship 271 00:18:21,150 --> 00:18:24,600 is far enough away that the partners 272 00:18:24,600 --> 00:18:27,513 are more than second cousins separated. 273 00:18:29,160 --> 00:18:31,966 Okay, one of the things we see quite often 274 00:18:31,966 --> 00:18:35,154 is assisted reproductive technology. 275 00:18:35,154 --> 00:18:40,154 That a couple, either same-sex couple or opposite-sex couple 276 00:18:42,330 --> 00:18:45,840 find that they need assisted reproductive technology 277 00:18:45,840 --> 00:18:48,090 and a donor of a sperm. 278 00:18:48,090 --> 00:18:53,090 In this case, the D represents a sperm donor, 279 00:18:53,092 --> 00:18:56,856 and a pregnancy is conceived between the egg 280 00:18:56,856 --> 00:19:01,856 from a female partner and the donated egg. 281 00:19:02,430 --> 00:19:04,740 So this is how you represent that 282 00:19:04,740 --> 00:19:09,420 in pedigree nomenclature. 283 00:19:09,420 --> 00:19:12,070 So notice that the line between the D 284 00:19:15,370 --> 00:19:19,320 and the fetus of the pregnancy is not horizontal. 285 00:19:19,320 --> 00:19:22,890 It's not representing a direct mating 286 00:19:22,890 --> 00:19:27,210 because there's not usually a formal relationship 287 00:19:27,210 --> 00:19:29,220 between the sperm donor 288 00:19:29,220 --> 00:19:34,220 and the person who's receiving the embryo. 289 00:19:34,350 --> 00:19:37,671 Sometimes there is, in which case you would draw a line 290 00:19:37,671 --> 00:19:42,671 between them, but it would be a dotted line 291 00:19:42,780 --> 00:19:47,703 because, by definition, if it's a donor, it's not a partner. 292 00:19:48,600 --> 00:19:49,433 All right. 293 00:19:51,744 --> 00:19:56,610 This is an example of a pedigree from Afghanistan. 294 00:19:56,610 --> 00:19:58,230 There are a number of places in the Middle East 295 00:19:58,230 --> 00:20:03,230 where the culture dictates that 296 00:20:03,540 --> 00:20:08,133 people marry someone within an extended family. 297 00:20:09,060 --> 00:20:13,150 And so there can be quite a lot of consanguinity 298 00:20:14,670 --> 00:20:17,040 represented in those family trees 299 00:20:17,040 --> 00:20:20,640 and it can be intergenerational as well. 300 00:20:20,640 --> 00:20:24,360 So sometimes these pedigrees get pretty complex 301 00:20:24,360 --> 00:20:27,360 and pretty hard to parse, 302 00:20:27,360 --> 00:20:30,513 but this is just an example of what that looks like. 303 00:20:33,750 --> 00:20:36,573 All right, so that's the end of this.