turtles-own [ homdom? ;; Person is homozygous dominant for the disease. het? ;; Person is heterozygous for the disease. homrec? ;; Person is homozygous recessive for the disease. coupled? ;; Person is in a relationship. partner ;; The person that is our current partner in a couple. num-children ;; Number of children a couple has already had. couple-length ;; How long a couple will stay together before separating. num-couples ;; Number of couples a person has been in. ] to setup clear-all reset-ticks create-turtles numpeople ask turtles [set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 set num-couples 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"] assign-genotypes assign-colors ] end to assign-genotypes ifelse (who < ( random-near .33 * numpeople)) [set homdom? true] [set homdom? false] ifelse ((homdom? = false) and (who < ( random-near .66 * numpeople))) [set het? true] [set het? false] ifelse ((homdom? = false) and (het? = false) and (who < numpeople)) [set homrec? true] [set homrec? false] if ((homdom? = false) and (het? = false) and (homrec? = false)) [die] end to assign-colors ask self [ if (homdom? = true) [set color blue] if (het? = true) [set color green] if (homrec? = true) [set color yellow] ] end to-report random-near [center] let result 0 repeat 40 [ set result (result + random-float center) ] report result / 20 end to go ask turtles [if not coupled? [move]] ask turtles [if (not coupled? and shape = "girl" and random 100 = 0) [couple]] ask turtles [if coupled? [set couple-length couple-length + 1]] ask turtles [if (coupled? and shape = "girl" and num-children <= avg-num-children and random 100 = 0) [assign-child-genotype]] ask turtles [if (coupled? and shape = "girl" and num-children >= avg-num-children) [uncouple]] ask turtles [ assign-colors ] mutate if (count turtles > 2000) [ask n-of 50 turtles [if not coupled? [die]]] if %homdom >= 100 [stop] tick end to move let dice random 2 let change (dice - 1) forward 2 set heading (heading + change * 2) end to couple let potential-partner one-of (turtles-at -1 0) with [(not coupled?) and shape = "boy"] if potential-partner != nobody [ set partner potential-partner set coupled? true set num-couples num-couples + 1 ask partner [set num-couples num-couples + 1 ] ask partner [ set coupled? true ] ask partner [ set partner myself ] move-to patch-here ask potential-partner [move-to patch-here] set pcolor gray - 3 ask (patch-at -1 0) [ set pcolor gray - 3 ] ] end to assign-child-genotype ask self [ if (homdom? and coupled?) [ask partner [if (homdom? and coupled?) ;; BB x BB pairing [hatch 1 [set homdom? true set het? false set homrec? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] let dice random 4 ask self [ if het? and coupled? [ask partner [if (homdom? and coupled? and dice > 2) ;; BB x Bb pairing [hatch 1 [set homdom? true set het? false set homrec? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] if het? and coupled? [ask partner [if (homdom? and coupled? and dice < 2) [hatch 1 [set het? true set homdom? false set homrec? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]]] if homrec? and coupled? [ask partner [if homdom? and coupled? ;; BB x bb pairing [hatch 1 [set het? true set homdom? false set homrec? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]]] let chance random 2 ask self [ if het? and coupled? [ask partner [if (het? and coupled? and chance = 0) ;; Bb x Bb pairing [hatch 1 [set homdom? true set het? false set homrec? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] if het? and coupled? [ask partner [if (het? and coupled? and chance = 1) [hatch 1 [set het? true set homdom? false set homrec? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] if het? and coupled? [ask partner [if (het? and coupled? and chance = 2) [hatch 1 [set homrec? true set homdom? false set het? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] if het? and coupled? [ask partner [if (homrec? and coupled? and chance > 1) ;; Bb x bb pairing [hatch 1 [set het? true set homdom? false set homrec? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] if het? and coupled? [ask partner [if (homrec? and coupled? and chance < 1) [hatch 1 [set homrec? true set homdom? false set het? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] if homrec? and coupled? [ask partner [if homrec? and coupled? ;; bb x bb pairing [hatch 1 [set homrec? true set homdom? false set het? false set shape "person" setxy random-xcor random-ycor set coupled? false set partner nobody set num-children 0 set couple-length 0 ifelse random 2 = 0 [set shape "girl"] [set shape "boy"]]]]] ] set num-children num-children + 1 ask partner [set num-children num-children + 1] end to uncouple if coupled? and (shape = "girl") [if ((num-children >= avg-num-children) or (couple-length >= avg-couple-length)) [ set coupled? false set couple-length 0 ask partner [set couple-length 0] set pcolor black ask (patch-at -1 0) [ set pcolor black ] ask partner [ set partner nobody ] ask partner [ set coupled? false ifelse num-couples >= avg-num-couples [die] [move]] set partner nobody]] ifelse num-couples >= avg-num-couples [die] [move] end to mutate if random-float 100 < mutation-rate [ask one-of turtles [if (homdom? = true) [set homdom? false set homrec? true]]] end to count-girls report turtles with [shape = "girl"] end to count-boys report turtles with [shape = "boy"] end to-report %homdom report count turtles with [homdom? = true] / count turtles end to-report %het report count turtles with [het? = true] / count turtles end to-report %homrec report count turtles with [homrec? = true] / count turtles end to-report num-dom-allele report ( ((count turtles with [homdom? = true]) * 2 ) + (count turtles with [het? = true])) / (count turtles * 2) end to-report num-rec-allele report ( ((count turtles with [homrec? = true]) * 2) + (count turtles with [het? = true])) / (count turtles * 2) end @#$#@#$#@ GRAPHICS-WINDOW 386 23 864 522 12 12 18.72 1 10 1 1 1 0 1 1 1 -12 12 -12 12 1 1 1 weeks 30.0 SLIDER 64 105 251 138 avg-num-children avg-num-children 0 5 5 1 1 NIL HORIZONTAL SLIDER 80 154 252 187 numpeople numpeople 0 500 300 10 1 NIL HORIZONTAL BUTTON 911 106 977 139 NIL setup\n NIL 1 T OBSERVER NIL NIL NIL NIL 1 BUTTON 914 156 977 189 NIL go\n T 1 T OBSERVER NIL NIL NIL NIL 0 PLOT 8 377 331 595 Genotype time people 0.0 100.0 0.0 100.0 true true "" "" PENS "Hom Rec" 1.0 0 -1184463 true "" "plot count turtles with [homrec? = true]" "Heterozygous" 1.0 0 -13840069 true "" "plot count turtles with [het? = true]" "Hom Dom" 1.0 0 -13345367 true "" "plot count turtles with [homdom? = true]" MONITOR 133 258 190 303 NIL ticks 17 1 11 MONITOR 20 318 99 363 % Hom Rec ((count turtles with [homrec? = true]) / count turtles) * 100 4 1 11 MONITOR 135 319 201 364 % Hetero (count turtles with [het? = true] / count turtles) * 100 4 1 11 MONITOR 237 320 323 365 % Hom Dom (count turtles with [homdom? = true] / count turtles) * 100 4 1 11 SLIDER 80 56 252 89 avg-couple-length avg-couple-length 100 3000 2000 10 1 NIL HORIZONTAL MONITOR 487 540 761 585 coupled? count turtles with [coupled? = true] 17 1 11 MONITOR 235 609 321 654 # Hom Dom count turtles with [homdom? = true] 17 1 11 MONITOR 138 608 204 653 # Hetero count turtles with [het? = true] 17 1 11 MONITOR 21 608 100 653 # Hom Rec count turtles with [homrec? = true] 17 1 11 MONITOR 488 607 601 652 Dom Allele Freq. num-dom-allele 3 1 11 MONITOR 655 607 761 652 Rec Allele Freq. num-rec-allele 3 1 11 SLIDER 80 200 252 233 avg-num-couples avg-num-couples 0 5 2 1 1 NIL HORIZONTAL MONITOR 774 540 867 585 NIL count turtles 17 1 11 SLIDER 79 10 251 43 mutation-rate mutation-rate 0 100 5 1 1 NIL HORIZONTAL @#$#@#$#@ ## WHAT IS IT? This model is a simplistic simulation of the spread of a genetic disease with an autosomal recessive inheritance pattern in a small, isolated human population. It illustrates how allelic frequencies vary from generation to generation. Genetic inheritance has risen to prominence as medical professionals have realized the implications of family health knowledge. Genetic diseases, indicators of heart, blood. and addiction problems, and even certain cancers can be predicted and measures can be taken to prevent the onset of these medical issues. Although genetic diseases are considered rare, twenty percent of all infant deaths are due to birth defects and genetic conditions.There are between 6,000 and 18,000 known single-gene disorders, affecting one in every 200 births, and only a small fraction of these have treatments. Additional study in this field could lead to the production of a wider range of more effective treatments and perhaps even cures for genetic diseases. The model examines the effects of certain variables on the allelic frequencies of the gene pool. The user controls several aspects of the child-bearing relationships modeled. Exploration of these variables can provide insight into the genetic trends scientists have observed in natural populations and show why recessive genes cannot become completely extinct. ## HOW IT WORKS The model uses "couples" to represent two people in a committed relationship. Individuals wander around the world when they are not in couples. Upon coming into contact with a partner, the two individuals "couple" together. When this happens, the two individuals no longer move about, and instead stand next to each other holding hands as a representation of their child-bearing relationship. Once in a couple, the two genotypes of the "parents" are considered before a child is born, and the child is then assigned a genotype based on Punnett square predictions of the parents' offspring. It is a 50/50 chance between the child being born a girl or boy. The genotypes of the individuals in the population are represented by the colors of the individuals. Three colors are used: blue individuals are homozygous dominant (AA), green individuals are heterozygous (Aa), and yellow individuals are homozygous recessive (aa). ## HOW TO USE IT The SETUP button creates individuals with certain genotypes and randomly distributes them throughout the world. Once the simulation has been setup, it is now ready to run. The GO button starts the simulation and runs it continuously, with a carrying capacity set at 2,000 individuals. Monitors show the percentage of individuals with each genotype as well as the frequency of each allele in the population. In this model each timestep is considered one month; the number of months that have passed is shown in the toolbar. Here is a summary of the sliders in the model. They are explained in more detail below. - numpeople - avg-num-children - avg-couple-length - mutation-rate - avg-num-couples Numpeople is used to determine the initial population at the start of the simulation. Smaller populations occasionally exhibit genetic drift (tendency towards either homozygous dominant or recessive). Avg-num-children is used to determine the average number of children a couple will have before splitting up. More children means more variety. Avg-couple-length is used to determine the amount of time a couple has spent in a relationship. Mutation rate is used to determine how often a de novo mutation arises in a "healthy" individual, causing them to contract the disease. Avg-num-couples is used to determine how many child-bearing relationships one person will be in before they die. The model's plot shows the total number of individuals (color), the number of homozygous dominant individuals (blue), the number of heterozygous individuals (green), and the number of homozygous recessive individuals (yellow). ## THINGS TO NOTICE If certain variables are set at low values, the population could eventually die out. As in real life, the dominant allele usually becomes more frequent in the gene pool than the recessive allele unless the mutation rate is unnaturally high. However, the recessive allele never truly becomes extinct due to de novo mutations. ## THINGS TO TRY Run a number of experiments with the GO button to find out the effects of different variable on the dominant and recessive allele frequencies. In addition to changing one variable at a time, try changing multiple variables together to see if those factors interact at all. Form hypotheses about how allelic frequencies will change with the adjustment of different variables and then test these to see if the results match your expectations. A few real-world values for some of the variables are included below: avg-num-children: U.S.A - between 1 and 2 Latin America - between 2 and 3 Middle East - between 3 and 5 avg-num-couples: roughly 1 avg-couple-length: 45 years (USA) mutation-rate: 2.22% ## EXTENDING THE MODEL Like all computer simulations of human behaviors, this model has necessarily simplified its subject area substantially. The model therefore provides numerous opportunities for extension: The model depicts a very simplistic gene at one locus controlled entirely by two alleles which exhibit complete dominance. In the real world, many genetic diseases are caused by a myriad of different factors. The model depicts an autosomal genetic disease. To extend the model further, one could model an x-linked disease or a case of genomic imprinting (expression of allele in offspring depends on whether allele is inherited from male or female parent). ## CREDITS AND REFERENCES All statistics in the Info tab come from the Centers for Disease Control and Prevention. The AIDS model in the NetLogo library was particularly helpful in setting up the coupling procedure: Wilensky, U. (1997). NetLogo AIDS model. http://ccl.northwestern.edu/netlogo/models/AIDS. Center for Connected Learning and Computer-Based Modeling, Northwestern Unversity, Evanston, IL. None of this would have been possible without the internship opportunity provided by the SEAP program and my mentor, Prof. Sanchez. @#$#@#$#@ default true 0 Polygon -7500403 true true 150 5 40 250 150 205 260 250 airplane true 0 Polygon -7500403 true true 150 0 135 15 120 60 120 105 15 165 15 195 120 180 135 240 105 270 120 285 150 270 180 285 210 270 165 240 180 180 285 195 285 165 180 105 180 60 165 15 arrow true 0 Polygon -7500403 true true 150 0 0 150 105 150 105 293 195 293 195 150 300 150 box false 0 Polygon -7500403 true true 150 285 285 225 285 75 150 135 Polygon -7500403 true true 150 135 15 75 150 15 285 75 Polygon -7500403 true true 15 75 15 225 150 285 150 135 Line -16777216 false 150 285 150 135 Line -16777216 false 150 135 15 75 Line -16777216 false 150 135 285 75 boy false 0 Circle -7500403 true true 110 5 80 Polygon -7500403 true true 105 90 120 195 90 285 105 300 135 300 150 195 165 300 195 300 210 285 180 195 195 90 Rectangle -7500403 true true 135 79 165 90 Polygon 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