Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain

<div>Increase frequency of DNA copy number variation (CNVs) in neural tissue compared to the blood. (a) The mean of the total CNVs detected in independent blood (<svg height="8.55521pt" id="M8" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 34.1002 8.55521" width="34.1002pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z" id="g113-111"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M412 140C382 77 369 73 315 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448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z" id="g113-111"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z" id="g113-56"></path></g><g transform="matrix(.013,0,0,-0.013,27.663,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g></svg>) samples; <span class="nowrap"><svg height="13.532pt" id="M10" style="vertical-align:-3.4295pt" version="1.1" viewbox="-0.0498162 -10.1025 74.2938 13.532" width="74.2938pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z" id="g50-43"></path></g><g transform="matrix(.0091,0,0,-0.0091,5.56,-5.741)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 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236C368 205 390 186 422 144C444 143 470 148 486 158Z" id="g50-43"></path></g><g transform="matrix(.013,0,0,-0.013,17.241,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z" id="g113-113"></path></g><g transform="matrix(.013,0,0,-0.013,28.583,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path></g><g transform="matrix(.013,0,0,-0.013,39.846,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" 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id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,67.77,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g></svg>,</span> Mann–Whitney <svg height="8.8423pt" id="M11" style="vertical-align:-0.2064009pt" version="1.1" viewbox="-0.0498162 -8.6359 9.58606 8.8423" width="9.58606pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M715 650H476L470 622C550 619 562 610 562 570C562 536 553 481 535 384L523 321C485 121 408 37 283 37C178 37 99 109 134 297L178 532C193 612 199 616 278 622L284 650H29L23 622C105 616 109 609 94 532L48 291C23 160 51 83 98 40C143 -1 202 -16 260 -16C321 -16 387 3 439 49C509 111 542 204 563 312L577 384C595 479 608 533 619 569C629 603 637 620 709 622L715 650Z" id="g113-86"></path></g></svg> test. (b) The mean of the total CNVs detected in paired blood and cerebellum samples from 19 random individuals; <span class="nowrap"><svg height="13.532pt" id="M12" style="vertical-align:-3.4295pt" version="1.1" viewbox="-0.0498162 -10.1025 62.4495 13.532" width="62.4495pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z" id="g50-43"></path></g><g transform="matrix(.0091,0,0,-0.0091,5.56,-5.741)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z" id="g50-43"></path></g><g transform="matrix(.013,0,0,-0.013,11.66,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z" id="g113-113"></path></g><g transform="matrix(.013,0,0,-0.013,23.002,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path></g><g transform="matrix(.013,0,0,-0.013,34.265,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,40.505,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path></g><g transform="matrix(.013,0,0,-0.013,43.469,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,49.709,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,55.949,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g></svg>,</span> Mann–Whitney <svg height="8.8423pt" id="M13" style="vertical-align:-0.2064009pt" version="1.1" viewbox="-0.0498162 -8.6359 9.58606 8.8423" width="9.58606pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M715 650H476L470 622C550 619 562 610 562 570C562 536 553 481 535 384L523 321C485 121 408 37 283 37C178 37 99 109 134 297L178 532C193 612 199 616 278 622L284 650H29L23 622C105 616 109 609 94 532L48 291C23 160 51 83 98 40C143 -1 202 -16 260 -16C321 -16 387 3 439 49C509 111 542 204 563 312L577 384C595 479 608 533 619 569C629 603 637 620 709 622L715 650Z" id="g113-86"></path></g></svg> test. (c) Example of a CNV absent in the blood and observed in the cerebellum. Images extracted from Genomic Workbench software.</div>

Neural Plasticity

Increased DNA Copy Number Variation Mosaicism in Elderly Human Brain

Figure 1