Genome-wide association study of extreme longevity in Drosophila melanogaster.
Genome-wide association study of extreme longevity in Drosophila melanogaster.
复制标题
果蝇极端长寿的全基因组关联研究。
DOI：
10.1093/gbe/evt180
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发表时间：
2014-01
影响因子：
3.3
通讯作者：
Long AD
中科院分区：
文献类型：
--
作者：
Burke MK;King EG;Shahrestani P;Rose MR;Long AD
人类长寿全基因组关联研究（GWAS）试图识别极老者与年轻对照样本中不同频率的等位基因。在这里，我们将 GWAS 方法应用于源自少数近交系创始人的黑腹果蝇“合成”种群。我们使用下一代 DNA 测序来估计年龄组中最年长的幸存个体的等位基因和单倍型频率，并将这些频率与同一队列中随机抽样个体的频率进行比较。我们在四个独立队列中使用了这种病例对照策略，并确定了基因组中八个显着差异的区域，可能含有与长寿相关的基因。通过对局部单倍型的影响进行建模，我们比基于标记的 GWAS 更有能力检测长寿基因富集的区域。最重要的区域出现在染色体末端或着丝粒附近，重组很少发生，这与这些区域含有影响寿命的无条件有害等位基因一致。正常重组区域中的基因富含与免疫功能相关的基因和参与氧化应激反应的基因家族。我们的实验群体之间的遗传分化与人类群体之间的遗传分化相当，这反过来表明，当小组具有不同的血统时，我们的结果可能有助于解释人类极端长寿关联研究中的异质信号。
Human genome-wide association studies (GWAS) of longevity attempt to identify alleles at different frequencies in the extremely old, relative to a younger control sample. Here, we apply a GWAS approach to “synthetic” populations of Drosophila melanogaster derived from a small number of inbred founders. We used next-generation DNA sequencing to estimate allele and haplotype frequencies in the oldest surviving individuals of an age cohort and compared these frequencies with those of randomly sampled individuals from the same cohort. We used this case–control strategy in four independent cohorts and identified eight significantly differentiated regions of the genome potentially harboring genes with relevance for longevity. By modeling the effects of local haplotypes, we have more power to detect regions enriched for longevity genes than marker-based GWAS. Most significant regions occur near chromosome ends or centromeres where recombination is infrequent, consistent with these regions harboring unconditionally deleterious alleles impacting longevity. Genes in regions of normal recombination are enriched for those relevant to immune function and a gene family involved in oxidative stress response. Genetic differentiation between our experimental cohorts is comparable to that between human populations, suggesting in turn that our results may help explain heterogeneous signals in human association studies of extreme longevity when panels have diverse ancestry.
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影响因子：
2.2
作者：
Burkhard, DU;Ward, PI;Blanckenhorn, WU
通讯作者：
Blanckenhorn, WU
影响因子：
3.3
作者：
King, Elizabeth G.;Macdonald, Stuart J.;Long, Anthony D.
通讯作者：
Long, Anthony D.
DOI：
10.1073/pnas.93.26.15249
发表时间：
1996-12-24
影响因子：
11.1
作者：
Mueller, LD;Rose, MR
通讯作者：
Rose, MR
影响因子：
3.5
作者：
Fiston-Lavier, Anna-Sophie;Singh, Nadia D.;Petrov, Dmitri A.
通讯作者：
Petrov, Dmitri A.
DOI：
10.1093/bioinformatics/btp698
发表时间：
2010-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li H;Durbin R
通讯作者：
Durbin R