A "forward genomics" approach links genotype to phenotype using independent phenotypic losses among related species.
A "forward genomics" approach links genotype to phenotype using independent phenotypic losses among related species.
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DOI：
10.1016/j.celrep.2012.08.032
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发表时间：
2012-10-25
期刊：
影响因子：
8.8
通讯作者：
Bejerano G
中科院分区：
文献类型：
--
作者：
Hiller M;Schaar BT;Indjeian VB;Kingsley DM;Hagey LR;Bejerano G
基因型-表型作图受到物种间无数基因组变化的阻碍。我们引入了一个计算的“正向基因组学”的策略，只有一个独立的丢失的表型和整个基因组-匹配基因组和表型的损失模式，将特定的基因组区域与这种表型。我们对两种代谢表型进行了全基因组筛选。首先，我们的方法正确地将失活的Gulo基因与失去合成维生素C能力的物种完全匹配。其次，我们将豚鼠和马的胆汁磷脂水平自然降低归因于磷脂转运蛋白Abcb 4失活。人类ABCB 4突变也会导致低磷脂水平，但会导致严重的肝脏疾病，这表明豚鼠和马的代偿机制。我们的模拟研究、现有表型调查中的独立变化计数以及即将出现的许多新基因组，都表明正向基因组学可以应用于许多表型，包括与人类进化和疾病相关的表型。
Genotype-phenotype mapping is hampered by countless genomic changes between species. We introduce a computational “forward genomics” strategy that – given only an independently lost phenotype and whole genomes – matches genomic and phenotypic loss patterns to associate specific genomic regions with this phenotype. We conducted genome-wide screens for two metabolic phenotypes. First, our approach correctly matches the inactivated Gulo gene exactly with the species that lost the ability to synthesize vitamin C. Second, we attribute naturally low biliary phospholipid levels in guinea pigs and horses to the inactivated phospholipid transporter Abcb4. Human ABCB4 mutations also result in low phospholipid levels, but lead to severe liver disease, suggesting compensatory mechanisms in guinea pig and horse. Our simulation studies, counts of independent changes in existing phenotype surveys and the forthcoming availability of many new genomes, all suggest that forward genomics can be applied to many phenotypes, including those relevant for human evolution and disease.
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影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W
DOI：
10.1016/s0304-4165(99)00123-3
发表时间：
1999-10-18
影响因子：
3
作者：
Ohta, Y;Nishikimi, M
通讯作者：
Nishikimi, M
影响因子：
29.4
作者：
PUGLIELLI, L;AMIGO, L;NERVI, F
通讯作者：
NERVI, F
影响因子：
7
作者：
Siepel, A;Bejerano, G;Haussler, D
通讯作者：
Haussler, D
影响因子：
64.8
作者：
Cheng, Z;Ventura, M;Eichler, EE
通讯作者：
Eichler, EE