Genome-wide identification of pseudogenes capable of disease-causing gene conversion
Genome-wide identification of pseudogenes capable of disease-causing gene conversion
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DOI：
10.1002/humu.20335
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发表时间：
2006-06-01
期刊：
影响因子：
3.9
通讯作者：
Braun, Terry A.
中科院分区：
文献类型：
--
作者：
Bischof, Jared M.;Chiang, Annie P.;Braun, Terry A.
假基因是基因复制（未加工的假基因）和反转录转座（加工的假基因）事件的残余。本研究描述了从预测的假基因中识别基因转换候选者的方法。假基因可能会随着时间的推移积累并携带序列变异，从而成为疾病，当通过基因转换转移到基因时会导致突变。共鉴定出14,476个假基因，包括3,426个未加工的假基因。此外，还评估了1，945个位于其祖基因附近的未加工假基因在基因转换和疾病中的可能作用。所有11个已知的，涉及假基因的人类基因转换（具有有害影响）病例都是通过这些方法成功鉴定的。在所鉴定的假基因中，有一种视网膜色素变性9（RP 9）假基因，其携带c.509A > G突变，该突变产生与RP 9形式的常染色体显性视网膜色素变性（adRP）相关的p.Asp170Gly取代。RP 9中的c.509A > G突变是先前未被认识到的祖基因与其假基因之间的基因转换的例子。值得注意的是，两个加工过的假基因也含有与疾病相关的突变。肌苷单磷酸脱氢酶1（IMPDH 1）假基因携带c.676G > A突变，产生p.Asp226Asn取代，导致视网膜色素变性10（RP 10）形式的adRP;磷酸甘油酸激酶1（PGK 1）假基因（PGK 1 P1）携带c.837T > C突变，产生p.Ile252Thr取代，与磷酸甘油酸激酶缺乏症相关。基于已发表的假基因介导的基因转换的序列特征，还对作为基因转换候选者的未加工假基因进行了排序。本研究产生的所有结果和工具可在http：//www.example.com下载。genome.uiowa.edu/pseudogenes
Pseudogenes are remnants of gene duplication (nonprocessed pseudogenes) and retrotransposition (processed pseudogenes) events. This study describes methods for identifying gene conversion candidates from predicted pseudogenes. Pseudogenes may accumulate and harbor sequence variations over time that become disease, causing mutations when transferred to genes by gene conversion. A total of 14,476 pseudogenes were identified, including 3,426 nonprocessed pseudogenes. In addition, 1,945 nonprocessed pseudogenes that are localized near their progenitor gene were evaluated for their possible role in gene conversion and disease. All 11 known, human cases of gene conversion (with deleterious effects) involving pseudogenes were successfully identified by these methods. Among the pseudogenes identified is a retinitis pigmentosa 9 (RP9) pseudogene that carries a c.509A > G mutation which produces a p.Asp170Gly substitution that is associated with the RP9 form of autosomal dominant retinitis pigmentosa (adRP). The c.509A > G mutation in RP9 is a previously unrecognized example of gene conversion between the progenitor gene and its pseudogene. Notably, two processed pseudogenes also contain mutations associated with diseases. An inosine monophosphate dehydrogenase 1 (IMPDH1) pseudogene carries a c.676G > A mutation that produces a p.Asp226Asn substitution that causes the retinitis pigmentosa 10 (RP10) form of adRP; and a phosphoglycerate kinase 1 (PGK1) pseudogene (PGK1P1) carries a c.837T > C mutation that produces a p.Ile252Thr substitution that is associated with a phosphoglycerate kinase deficiency. Ranking of nonprocessed pseudogenes as candidates for gene conversion was also performed based on the sequence characteristics of published cases of pseudogene-mediated gene conversion. All results and tools produced by this study are available for download at: http:// genome.uiowa.edu/pseudogenes.