Aging and neurodegeneration are associated with increased mutations in single human neurons.
Aging and neurodegeneration are associated with increased mutations in single human neurons.
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DOI：
10.1126/science.aao4426
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发表时间：
2018-02-02
期刊：
影响因子：
--
通讯作者：
Walsh CA
中科院分区：
文献类型：
--
作者：
Lodato MA;Rodin RE;Bohrson CL;Coulter ME;Barton AR;Kwon M;Sherman MA;Vitzthum CM;Luquette LJ;Yandava CN;Yang P;Chittenden TW;Hatem NE;Ryu SC;Woodworth MB;Park PJ;Walsh CA
长期以来，人们一直假设衰老和神经退行性变与神经元的体细胞突变有关;然而，方法上的障碍阻碍了直接验证这一假设。我们使用单细胞全基因组测序进行全基因组体细胞单核苷酸变异（sSNV）鉴定的DNA从161个单神经元的前额叶皮层和海马的15个正常人（年龄4个月至82岁），以及9个人受早发性神经退行性疾病，由于遗传疾病的DNA修复（Cockayne综合征和着色性干皮病）。sSNV在两个区域中随着年龄的增长而近似线性地增加（在海马中具有更高的速率），并且在神经退行性疾病中更丰富。随着年龄的增长，体细胞突变的积累-我们称之为基因突变-显示出与年龄相关、与区域相关和与疾病相关的分子特征，并且可能在其他与年龄相关的人类疾病中很重要。
It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of fifteen normal individuals (aged 4 months to 82 years) as well as nine individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and Xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age—which we term genosenium—shows age-related, region-related, and disease-related molecular signatures, and may be important in other human age-associated conditions.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
影响因子：
3.1
作者：
van Veluw, Susanne J.;Sawyer, Eva K.;Chance, Steven A.
通讯作者：
Chance, Steven A.
影响因子：
16.2
作者：
Hazen JL;Faust GG;Rodriguez AR;Ferguson WC;Shumilina S;Clark RA;Boland MJ;Martin G;Chubukov P;Tsunemoto RK;Torkamani A;Kupriyanov S;Hall IM;Baldwin KK
通讯作者：
Baldwin KK