<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Nuttle, Xander</style></author><author><style face="normal" font="default" size="100%">Giannuzzi, Giuliana</style></author><author><style face="normal" font="default" size="100%">Duyzend, Michael H.</style></author><author><style face="normal" font="default" size="100%">Schraiber, Joshua G.</style></author><author><style face="normal" font="default" size="100%">Narvaiza, Iñigo</style></author><author><style face="normal" font="default" size="100%">Sudmant, Peter H.</style></author><author><style face="normal" font="default" size="100%">Penn, Osnat</style></author><author><style face="normal" font="default" size="100%">Chiatante, Giorgia</style></author><author><style face="normal" font="default" size="100%">Malig, Maika</style></author><author><style face="normal" font="default" size="100%">Huddleston, John</style></author><author><style face="normal" font="default" size="100%">Benner, Chris</style></author><author><style face="normal" font="default" size="100%">Camponeschi, Francesca</style></author><author><style face="normal" font="default" size="100%">Ciofi-Baffoni, Simone</style></author><author><style face="normal" font="default" size="100%">Stessman, Holly A. F.</style></author><author><style face="normal" font="default" size="100%">Marchetto, Maria C. N.</style></author><author><style face="normal" font="default" size="100%">Denman, Laura</style></author><author><style face="normal" font="default" size="100%">Harshman, Lana</style></author><author><style face="normal" font="default" size="100%">Baker, Carl</style></author><author><style face="normal" font="default" size="100%">Raja, Archana</style></author><author><style face="normal" font="default" size="100%">Penewit, Kelsi</style></author><author><style face="normal" font="default" size="100%">Janke, Nicolette</style></author><author><style face="normal" font="default" size="100%">Tang, W. Joyce</style></author><author><style face="normal" font="default" size="100%">Ventura, Mario</style></author><author><style face="normal" font="default" size="100%">Banci, Lucia</style></author><author><style face="normal" font="default" size="100%">Antonacci, Francesca</style></author><author><style face="normal" font="default" size="100%">Akey, Joshua M.</style></author><author><style face="normal" font="default" size="100%">Amemiya, Chris T.</style></author><author><style face="normal" font="default" size="100%">Gage, Fred H.</style></author><author><style face="normal" font="default" size="100%">Reymond, Alexandre</style></author><author><style face="normal" font="default" size="100%">Eichler, Evan E.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility</style></title><secondary-title><style face="normal" font="default" size="100%">Nature</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">08/2016</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">http://dx.doi.org/10.1038/nature19075</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">advance online publication</style></volume><pages><style face="normal" font="default" size="100%"> </style></pages><isbn><style face="normal" font="default" size="100%">1476-4687</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Genetic differences that specify unique aspects of human evolution have typically been identified by comparative analyses between the genomes of humans and closely related primates&lt;a href=&quot;http://www.nature.com/nature/journal/v536/n7615/full/nature19075.html#ref1&quot; id=&quot;ref-link-13&quot; title=&quot;King, M. C. &amp;amp; Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975)&quot;&gt;1&lt;/a&gt;, including more recently the genomes of archaic hominins&lt;a href=&quot;http://www.nature.com/nature/journal/v536/n7615/full/nature19075.html#ref2&quot; id=&quot;ref-link-14&quot; title=&quot;Prüfer, K. et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43–49 (2014)&quot;&gt;2&lt;/a&gt;,&amp;nbsp;&lt;a href=&quot;http://www.nature.com/nature/journal/v536/n7615/full/nature19075.html#ref3&quot; id=&quot;ref-link-15&quot; title=&quot;Meyer, M. et al. A high-coverage genome sequence from an archaic Denisovan individual. Science 338, 222–226 (2012)&quot;&gt;3&lt;/a&gt;. Not all regions of the genome, however, are equally amenable to such study. Recurrent copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1% of cases of autism&lt;a href=&quot;http://www.nature.com/nature/journal/v536/n7615/full/nature19075.html#ref4&quot; id=&quot;ref-link-16&quot; title=&quot;Weiss, L. A. et al. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358, 667–675 (2008)&quot;&gt;4&lt;/a&gt;,&amp;nbsp;&lt;a href=&quot;http://www.nature.com/nature/journal/v536/n7615/full/nature19075.html#ref5&quot; id=&quot;ref-link-17&quot; title=&quot;Kumar, R. A. et al. Recurrent 16p11.2 microdeletions in autism. Hum. Mol. Genet. 17, 628–638 (2008)&quot;&gt;5&lt;/a&gt;&amp;nbsp;and is mediated by a complex set of segmental duplications, many of which arose recently during human evolution. Here we reconstruct the evolutionary history of the locus and identify bolA family member 2 (BOLA2) as a gene duplicated exclusively in&amp;nbsp;Homo sapiens. We estimate that a 95-kilobase-pair segment containing&amp;nbsp;BOLA2&amp;nbsp;duplicated across the critical region approximately 282 thousand years ago (ka), one of the latest among a series of genomic changes that dramatically restructured the locus during hominid evolution. All humans examined carried one or more copies of the duplication, which nearly fixed early in the human lineage—a pattern unlikely to have arisen so rapidly in the absence of selection (P &amp;lt; 0.0097). We show that the duplication ofBOLA2&amp;nbsp;led to a novel, human-specific in-frame fusion transcript and that&amp;nbsp;BOLA2copy number correlates with both RNA expression (r = 0.36) and protein level (r = 0.65), with the greatest expression difference between human and chimpanzee in experimentally derived stem cells. Analyses of 152 patients carrying a chromosome 16p11.2 rearrangement show that more than 96% of breakpoints occur within the&amp;nbsp;H. sapiens-specific duplication. In summary, the duplicative transposition of&amp;nbsp;BOLA2&amp;nbsp;at the root of the&amp;nbsp;H. sapiens&amp;nbsp;lineage about 282 ka simultaneously increased copy number of a gene associated with iron homeostasis and predisposed our species to recurrent rearrangements associated with disease.&lt;/p&gt;
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