Rate of de novo mutations and the importance of father's age to disease risk.
Rate of de novo mutations and the importance of father's age to disease risk.
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DOI：
10.1038/nature11396
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发表时间：
2012-08-23
期刊：
影响因子：
64.8
通讯作者：
Stefansson K
中科院分区：
文献类型：
--
作者：
Kong A;Frigge ML;Masson G;Besenbacher S;Sulem P;Magnusson G;Gudjonsson SA;Sigurdsson A;Jonasdottir A;Jonasdottir A;Wong WS;Sigurdsson G;Walters GB;Steinberg S;Helgason H;Thorleifsson G;Gudbjartsson DF;Helgason A;Magnusson OT;Thorsteinsdottir U;Stefansson K
突变产生序列多样性并提供选择的底物。因此，从头突变的速率对进化至关重要。我们通过对78个冰岛亲子三人组的全基因组进行测序，进行了全基因组突变率的研究。在这里，我们表明，在我们的样本中，父亲的平均年龄为29.7岁，平均从头突变率为每代每个核苷酸1.20×10−8。最引人注目的是，单核苷酸多态性（SNP）突变率的多样性主要受父亲受孕时的年龄影响。其影响是每年增加约2个突变。在考虑随机泊松变异后，估计父亲的年龄可以解释几乎所有的从头突变计数的剩余变异。这些观察揭示了父亲年龄对患精神分裂症和自闭症等疾病风险的重要性。
Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. We conducted a study of genomewide mutation rate by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. Here 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 strikingly, the diversity in mutation rate of single-nucleotide polymorphism (SNP) is dominated by the age of the father at conception of the child. The effect is an increase of about 2 mutations per year. 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.
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影响因子：
5.3
作者：
Gauthier J;Siddiqui TJ;Huashan P;Yokomaku D;Hamdan FF;Champagne N;Lapointe M;Spiegelman D;Noreau A;Lafrenière RG;Fathalli F;Joober R;Krebs MO;DeLisi LE;Mottron L;Fombonne E;Michaud JL;Drapeau P;Carbonetto S;Craig AM;Rouleau GA
通讯作者：
Rouleau GA
影响因子：
30.8
作者：
Sulem, Patrick;Gudbjartsson, Daniel F.;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
64.8
作者：
COULONDRE, C;MILLER, JH;GILBERT, W
通讯作者：
GILBERT, W
DOI：
10.1016/j.cub.2009.07.032
发表时间：
2009-09-15
期刊：
Current biology : CB
影响因子：
--
作者：
Xue Y;Wang Q;Long Q;Ng BL;Swerdlow H;Burton J;Skuce C;Taylor R;Abdellah Z;Zhao Y;Asan;MacArthur DG;Quail MA;Carter NP;Yang H;Tyler-Smith C
通讯作者：
Tyler-Smith C
影响因子：
64.8
作者：
Boyden, Lynn M.;Choi, Murim;Choate, Keith A.;Nelson-Williams, Carol J.;Farhi, Anita;Toka, Hakan R.;Tikhonova, Irina R.;Bjornson, Robert;Mane, Shrikant M.;Colussi, Giacomo;Lebel, Marcel;Gordon, Richard D.;Semmekrot, Ben A.;Poujol, Alain;Valimaki, Matti J.;De Ferrari, Maria E.;Sanjad, Sami A.;Gutkin, Michael;Karet, Fiona E.;Tucci, Joseph R.;Stockigt, Jim R.;Keppler-Noreuil, Kim M.;Porter, Craig C.;Anand, Sudhir K.;Whiteford, Margo L.;Davis, Ira D.;Dewar, Stephanie B.;Bettinelli, Alberto;Fadrowski, Jeffrey J.;Belsha, Craig W.;Hunley, Tracy E.;Nelson, Raoul D.;Trachtman, Howard;Cole, Trevor R. P.;Pinsk, Maury;Bockenhauer, Detlef;Shenoy, Mohan;Vaidyanathan, Priya;Foreman, John W.;Rasoulpour, Majid;Thameem, Farook;Al-Shahrouri, Hania Z.;Radhakrishnan, Jai;Gharavi, Ali G.;Goilav, Beatrice;Lifton, Richard P.
通讯作者：
Lifton, Richard P.