亿万富翁研究组Nature解析自发突变

　　

生物通报道：来自解码基因公司，丹麦奥胡斯大学等处的研究人员通过大规模基因组分析，发现大龄男性所育子女出现基因突变的概率更高，患与基因相关的精神分裂症、自闭症及其它疾病的风险也更大。这指出如果确实父亲年龄会导致后代的健康问题，那么建议年轻时可以保存精子，用于孕育后代。相关成果公布在Nature杂志上。

领导这一研究的是解码基因公司的Kari Stefansson，这位解码基因公司创始人的科学家在辞去哈佛医学院职务的四年后，就成了冰岛最富有的人，他从一个靠工资为生的教授一跃成为今天拥有净资产4亿美元的亿万富翁。近期入选了Times杂志评选的全球最有影响力百人“英雄与先驱”类。

关于父亲年龄与后代健康这个话题，其实由来已久，早在好几年前，澳大利亚昆士兰大学的John McGrath研究组就分析了1959年到1965年间出生的3.3万名美国人的资料。他们在8个月、4岁和7岁时接受了测试。研究人员发现，在各种认知测验中，父亲年龄较大的孩子所得分数远比那些父亲比较年轻的孩子低。

随后也有不少研究证明了这一关联，2010年Stefansson研究组发表文章，指出父母遗传物质作用不相同，父母双方遗传物质不仅重组的方式有侧重，重组的程度也不一样。卵子中遗传物质重组的程度高于精子。而导致基因差异和人类多样性的原因除遗传重组外，还有基因突变等，而研究显示男性精子的基因突变程度要高于女性的卵子。

在这一基础上，这一研究组展开了迄今为止最大规模的父本母本后代的研究，他们分析了78个来自冰岛的父母和后代，发现从20岁开始，男性每推迟一年生育子女，其后代基因中就会多出现两种突变基因。与此相比，母亲遗传给子女的突变基因约为15个，并且与她们的年龄无关。

这项研究指出20岁之前当父亲，和40岁之后当父亲的后代健康方面的差异，相当于每个后代自发突变积累导致的人类健康平均跌幅的一半。现代人类受到的自然选择压力小了很多，由于恶性突变比有益突变更为常见，因此这种轻松选择背后的进化必将导致人群身体素质的下降。

事实上，数据表明这种下降的趋势相对快。因此假设人类换上自闭症的增长趋势越来越快，也是合理的，这也是部分由于选择压力下，和父辈年龄平均增大的一个共同积累结果。

McGrath教授对此评价道，许多突变基因不会对个人健康造成影响，但是它们的累积效应却会成为“突变定时炸弹”，如果我们的社会继续推迟生育年龄，可能导致一系列紊乱症发生。

如果确实父亲年龄会导致后代的健康问题，那么建议年轻时可以保存精子，用于孕育后代。这对于公共健康来说也许是有价值的，正如这项研究中指出的，也许可以显著减少人类群体在选择压力降低后，基因池中出现恶性突变的发生率。

（生物通：张迪）

附：

时代杂志全球最有影响力百人
英雄与先驱

Oprah Winfrey
奥普拉.盖尔.温芙瑞是美国最成功的企业家和电视节目主持人之一。作为一名黑人，更为当今世界上最具影响力的妇女之一，她的成就是多方面的：拥有超过10亿美元的个人财富；主持的电视谈话节目“奥普拉脱口秀”，平均每周吸引3300万名观众，并连续16年排在同类节目的首位。
"Oprah Winfrey's own story is an inspiration because she overcame almost every obstacle that a person might face. She is an icon to people all over the world because of her commitment to help those who have faced similar obstacles."-Nelson Mandela

Elizabeth Edwards
虽然乳癌扩散，伊丽莎白·爱德华兹还是非常支持有意参选2008年美国总统的丈夫－－民主党前参议员约翰·爱德华兹（John Edwards）。伊丽莎白在2004年底被确诊为乳癌患者。她说过：“如果我放弃了一生的追求，就等于向癌症投降。也许癌症会最终战胜我，但我要抢在癌症前面打一场胜仗。”
"Cancer touches everyone around it and can bring wisdom and learning. Learning to love and let go. We all admire Elizabeth for her courage against these odds."-Melissa Etheridge

Warren Buffett
沃伦·巴菲特从小就极具投资意识，1941年，11岁的巴菲特购买了平生第一张股票。他还说过应该更早开始投资。1964年，巴菲特的个人财富达到400万美元，而当时他掌管的资金已高达2200万美元。多年来，在《福布斯》一年一度的全球富豪榜上，巴菲特一直稳居前三名。
"Last year Warren Buffett stunned us all with his incredible gift of $31 billion to the Bill & Melinda Gates Foundation. His generosity will make a huge difference in the lives of people around the world, and his example will be talked about for decades."-Melinda Gates

Drew Gilpin Faust
德鲁.吉尔平.福斯特是著名哈佛大学的28任校长，也是该校371年历史上的首位女校长。在这之前，她是拉德克利夫高级研究学院(Radcliffe Institute of Advanced Study)的院长。
"Faust, 59, has a lot on her plate—placating an often unwieldy and ego-driven faculty, making a Harvard education relevant in today's world, underwriting lower- and middle-class students who can't afford to pay—but already, by her sheer presence, she sends a message to every 19- or 20-year-old who dreams of going up against the odds: you can do it too."-Soledad O'Brien

Wesley Autrey
纽约的“地铁英雄”在面对急驶过来的列车时，勇敢跳下地铁月台救助一名因病而跌入轨道的学生。
"Autrey automatically became an influential person by merit of his extraordinary bravery, which I hope will encourage and inspire other people to follow his example."-Donald J. Trump

Tony Dungy
Tony Dungy是NFL里最优秀的教练之一，也是NFL里最受尊敬的教练之一。从小马的队员到其他球队的队员, 从NFL的教练到管理人员, 对Dungy的人品和教导风格都赞不绝口。
"Most people think football coaches have to scream and intimidate. Tony, 51, has taken the opposite approach."-Lovie Smith

Roger Federer
费德勒是世界网球高手。从19岁，费德勒作为瑞士新一代球员的领军人物时，就被很多网坛前辈所看好有能力在世界男子网坛做出一番惊天动地的成绩出来，甚至费德勒还被球迷冠以“桑普拉斯”接班人的称号。
毫无疑问，这位25岁的瑞士人已经在当今的网球世界中拥有了至尊地位。
"The most impressive aspect of Roger Federer's ascendancy to the top of the tennis world is the way he carries himself as a champion. It's quite unusual. He just lets his racquet do the talking."-Rod Laver

Amr Khaled
Amr Khaled或许在西方不知名，不过对回教徒来说，他是个名人。Amr Khaled是名传教师，而让他在世界舞台成名的是他主动在丹麦辱回教先知的卡通刊登之后，举办一个多元文化论坛，试图化解风波。
"Amr Khaled is not a household name in the West. But for a segment of the Islamic world, the 39-year-old Egyptian is a rock star."-Asra Nomani

王建民
王建民是台湾知名的棒球选手，目前效力于美国职棒大联盟的纽约洋基队。
"The Yankees ace won 19 games last year, and as runner-up for the Cy Young Award, he is a rising star. In his island home, he is already a supernova."-Betty Bao Lord

Chris Anderson
1961年出生的Chris Anderson是《连线》杂志的主编，他因提出长尾理论而名声大噪。长尾的提出是Chris基于他对娱乐市场的观察而得出的。通过对传统娱乐业和网络娱乐业的对比，Chris发现由于成本和规模的限制，传统娱乐业只能覆盖那些20%的主流而忽略了后面的尾巴。但是，网络技术解决了这个问题，使得在保证收益的前提下，满足了更多消费者的需求，这就是所谓的长尾。
"Truly Big Ideas are the rarest of phenomena, and when I first came upon Chris Anderson's The Long Tail last year, I knew this was one."-Malcolm Gladwell

Garry Kasparov
加利·卡斯巴罗夫，俄罗斯国际象棋棋手，国际象棋大师，前国际象棋世界冠军。曾在1999年7月取得FIDE评为 2851国际等级分。在1985年至2006年间曾23次获得世界排名第一。曾11次取得国际象棋奥斯卡奖。
"Garry Kasparov likes to say he has been in politics all his life. In the Soviet Union, the nation in which he grew up, chess was a way of demonstrating the superiority of communism over the decadent West, and a chess prodigy was inevitably a political figure. "-Michael Elliott

George Clooney
George Timothy Clooney，美国肯塔基州Lexington出生，美国演员，导演及编剧，2006年夺得第78届奥斯卡金像奖最佳男配角奖。以演出长篇电视剧ER(1994年–1999年)著名，并跻身好莱坞一线影星的行列。
"Clooney, 46, took his family with him to Darfur on his first trip there in 2006, and together they made A Journey to Darfur, which aired on the AmericanLife network. The actor returned to the U.S. as a consistent advocate for action in that war-ravaged region."-Ishmael Beah

Judith Mackay
居港40多年，英籍麦龙诗迪教授毕生致力控烟运动，与烟草集团抗争多年，美国支持吸烟的组识曾谩骂和讥讽她，恐吓说要置她于死地，但她并没有屈服。
"When looking at the actions of Judith Mackay, it is clear that she is moved by a profound desire to do good for others and that this desire has defined the course of her life. It led her to become first a practicing physician and then, since 1984, a tireless tobacco-control advocate. "-Jeffrey Wigand

Kari Stefansson
解码基因公司创始人Kari Stefansson，他在辞去哈佛医学院职务的四年后就成了冰岛最富有的人。他从一个靠工资为生的教授一跃成为今天拥有净资产4亿美元的富翁。
"Like many other Icelanders, neurologist Kari Stefansson can trace his lineage back to a single Viking, and that got him
thinking about the genetic roots of disease. "-Jeremy Caplan

Maher Arar
因为加拿大警方误将Maher Arar指认为伊斯兰极端分子，Maher Arar遭美国情报人员遣送叙利亚。阿拉尔是出生于叙利亚的加拿大公民。2002年，他度假后返回加拿大，在美国纽约短期停留时被捕。
"Maher Arar, 36, was returning home from a vacation in
September 2002 when U.S. federal agents detained him in New York City on suspicion of ties to terrorism. The U.S. government sent him to Syria, a nation with a history of engaging in torture. "-Patrick Leahy

Michael J. Fox
身高仅有5尺4寸的米高来自一个五个兄妹的军人家庭，15岁就开始在加国电视台演出，18岁转往美国发展，三年后以电视影集《天才家庭》成为80年代的青春偶像，85年起主演《回到未来》系列电影更红透半边天。虽然他曾在《越战创伤》等片尝试较为成熟稳重的角色，不过浪漫喜剧路线仍最受观众喜爱。97年因电视影集《Spin City》再度获得金球奖肯定。年前发现患上了帕金森综合症,现在他正和病魔做顽强的斗争。
"People sometimes veer into their own legacy after being blindsided by fate. Michael J. Fox is one of those people. "-Patti Davis

Thierry Henry
Thierry Henry是一名法国著名足球员，司职前锋，现效力英格兰球会阿森纳，他是现役法国国脚及目前阿森纳最高入球纪录的保持者，2003年至2004年英格兰足球先生及四届法国足球先生得主。
"Thierry, 29, is so much more than a great soccer player who helped France reach last year's World Cup final and who has led his English club team, Arsenal, to four national-cup wins. He wants to change the world."-Tony Parker

Timothy Gittins
Timothy Gittins是名美国军人，曾被派到伊拉克及阿富汗。他曾在美国攻打阿富汗时受伤，可以这么说，Timothy Gittins是典型处在战争热带的美国军人的勇敢象征。
"History has thrust Gittins into America's hot zones in Afghanistan and Iraq. He was deployed deep in Afghanistan's Shah-i-Kot valley battling—and being wounded by—the Taliban during Operation Anaconda in 2002."-Mark Thompson

Tyra Banks
Tyra Banks来自美国的非裔前超级名模、演员、歌手、电视制作人以及脱口秀主持。她现在是《全美超级模特儿新秀大赛》的主持人及评判。她过去亦是高级内衣品牌《维多利亚的秘密》的模特儿。泰拉亦有“超模之母”的美誉。
"Tyra Banks has used her own weight gain, the easy target of misogynist tabloids, as a teachable moment to confront the culture and speak out to girls and young women about embracing their bodies in all sizes. "-Naomi Wolf

Youk Chhang
Youk Chhang尽他的能力，尝试记录红高棉政权的屠杀事件。要翻开这个惨痛的历史，对每个人不容易，不过对Youk Chhang来说，这项工作有个人意义，因为他的家人就是在那个时候遇害的。
"Cambodia is like broken glass," says Youk Chhang, director of the Documentation Center of Cambodia. "Without justice, we cannot put the pieces together." Putting the pieces together is the mission of the man who made himself the keeper of Cambodia's darkest memories. "-John Kerry

曾金燕
曾金燕是一位民间环保人士和艾滋病活动人士，长期以来为河南等地的艾滋病人做了很多默默无闻的工作。
"Zeng Jinyan is the online progeny of the protester who blocked a column of advancing tanks during China's Tiananmen uprising in 1989. "-Arianna Huffington

原文摘要：

Rate of de novo mutations and the importance of father’s age to disease risk

Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent–offspring trios at high coverage. We show that in our samples, with an average father’s age of 29.7, the average de novo mutation rate is 1.20 × 10−8 per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5 years. After accounting for random Poisson variation, father’s age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father’s age on the risk of diseases such as schizophrenia and autism.