<?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%">Jónsson, Hákon</style></author><author><style face="normal" font="default" size="100%">Sulem, Patrick</style></author><author><style face="normal" font="default" size="100%">Kehr, Birte</style></author><author><style face="normal" font="default" size="100%">Kristmundsdottir, Snaedis</style></author><author><style face="normal" font="default" size="100%">Zink, Florian</style></author><author><style face="normal" font="default" size="100%">Hjartarson, Eirikur</style></author><author><style face="normal" font="default" size="100%">Hardarson, Marteinn T.</style></author><author><style face="normal" font="default" size="100%">Hjorleifsson, Kristjan E.</style></author><author><style face="normal" font="default" size="100%">Eggertsson, Hannes P.</style></author><author><style face="normal" font="default" size="100%">Gudjonsson, Sigurjon Axel</style></author><author><style face="normal" font="default" size="100%">Ward, Lucas D.</style></author><author><style face="normal" font="default" size="100%">Arnadottir, Gudny A.</style></author><author><style face="normal" font="default" size="100%">Helgason, Einar A.</style></author><author><style face="normal" font="default" size="100%">Helgason, Hannes</style></author><author><style face="normal" font="default" size="100%">Gylfason, Arnaldur</style></author><author><style face="normal" font="default" size="100%">Jonasdottir, Adalbjorg</style></author><author><style face="normal" font="default" size="100%">Jonasdottir, Aslaug</style></author><author><style face="normal" font="default" size="100%">Rafnar, Thorunn</style></author><author><style face="normal" font="default" size="100%">Frigge, Mike</style></author><author><style face="normal" font="default" size="100%">Stacey, Simon N.</style></author><author><style face="normal" font="default" size="100%">Th. Magnusson, Olafur</style></author><author><style face="normal" font="default" size="100%">Thorsteinsdottir, Unnur</style></author><author><style face="normal" font="default" size="100%">Masson, Gisli</style></author><author><style face="normal" font="default" size="100%">Kong, Augustine</style></author><author><style face="normal" font="default" size="100%">Halldorsson, Bjarni V.</style></author><author><style face="normal" font="default" size="100%">Helgason, Agnar</style></author><author><style face="normal" font="default" size="100%">Gudbjartsson, Daniel F.</style></author><author><style face="normal" font="default" size="100%">Stefansson, Kari</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Parental influence on human germline de novo mutations in 1,548 trios from            Iceland</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%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017/09/20</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.nature.com/nature/journal/vaop/ncurrent/full/nature24018.html</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;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;The characterization of mutational processes that generate sequence diversity in the human genome is of paramount importance both to medical genetics&lt;/span&gt;&lt;sup style=&quot;font-size: 12.320749282836914px; line-height: 0; color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-weight: bold;&quot;&gt;&lt;a href=&quot;https://www.nature.com/nature/journal/vaop/ncurrent/full/nature24018.html#ref1&quot; id=&quot;ref-link-1&quot; style=&quot;color: rgb(92, 121, 150); text-decoration: none; clear: both;&quot; title=&quot;Veltman, J. A. &amp;amp; Brunner, H. G. De novo mutations in human genetic disease. Nat. Rev. Genet. 13, 565–575 (2012)&quot;&gt;1&lt;/a&gt;,&amp;nbsp;&lt;a href=&quot;https://www.nature.com/nature/journal/vaop/ncurrent/full/nature24018.html#ref2&quot; id=&quot;ref-link-2&quot; style=&quot;color: rgb(92, 121, 150); text-decoration: none; clear: both;&quot; title=&quot;Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013)&quot;&gt;2&lt;/a&gt;&lt;/sup&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;&amp;nbsp;and to evolutionary studies&lt;/span&gt;&lt;sup style=&quot;font-size: 12.320749282836914px; line-height: 0; color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-weight: bold;&quot;&gt;&lt;a href=&quot;https://www.nature.com/nature/journal/vaop/ncurrent/full/nature24018.html#ref3&quot; id=&quot;ref-link-3&quot; style=&quot;color: rgb(92, 121, 150); text-decoration: none; clear: both;&quot; title=&quot;Scally, A. &amp;amp; Durbin, R. Revising the human mutation rate: implications for understanding human evolution. Nat. Rev. Genet. 13, 745–753 (2012)&quot;&gt;3&lt;/a&gt;&lt;/sup&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;. To understand how the age and sex of transmitting parents affect&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;de novo&lt;/i&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;&amp;nbsp;mutations, here we sequence 1,548 Icelanders, their parents, and, for a subset of 225, at least one child, to 35× genome-wide coverage. We find 108,778&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;de novo&lt;/i&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;&amp;nbsp;mutations, both single nucleotide polymorphisms and indels, and determine the parent of origin of 42,961. The number of&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;de novo&lt;/i&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;&amp;nbsp;mutations from mothers increases by 0.37 per year of age (95% CI 0.32–0.43), a quarter of the 1.51 per year from fathers (95% CI 1.45–1.57). The number of clustered mutations increases faster with the mother’s age than with the father’s, and the genomic span of maternal&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;de novo&lt;/i&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;&amp;nbsp;mutation clusters is greater than that of paternal ones. The types of&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;de &lt;/i&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;novo&lt;/i&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;mutation&lt;/span&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt; from mothers change substantially with age, with a 0.26% (95% CI 0.19–0.33%) decrease in cytosine–phosphate–guanine to thymine–phosphate–guanine (CpG&amp;gt;TpG)&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;de novo&lt;/i&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;&amp;nbsp;mutations and a 0.33% (95% CI 0.28–0.38%) increase in C&amp;gt;G&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;de novo&lt;/i&gt;&lt;span style=&quot;color: rgb(51, 51, 51); font-family: arial, helvetica, &#039;ＭＳ Ｐゴシック&#039;, &#039;ＭＳ ゴシック&#039;, Osaka, &#039;MS PGothic&#039;, sans-serif; font-size: 14.494999885559082px; font-weight: bold;&quot;&gt;&amp;nbsp;mutations per year, respectively. Remarkably, these age-related changes are not distributed uniformly across the genome. A striking example is a 20 megabase region on chromosome 8p, with a maternal C&amp;gt;G mutation rate that is up to 50-fold greater than the rest of the genome. The age-related accumulation of maternal non-crossover gene conversions also mostly occurs within these regions. Increased sequence diversity and linkage disequilibrium of C&amp;gt;G variants within regions affected by excess maternal mutations indicate that the underlying mutational process has persisted in humans for thousands of years. Moreover, the regional excess of C&amp;gt;G variation in humans is largely shared by chimpanzees, less by gorillas, and is almost absent from orangutans. This demonstrates that sequence diversity in humans results from evolving interactions between age, sex, mutation type, and genomic location.&lt;/span&gt;&lt;/p&gt;
</style></abstract></record></records></xml>