Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus.
Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus.
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DOI：
10.1371/journal.pone.0057281
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jeffery WR
中科院分区：
文献类型：
--
作者：
O'Quin KE;Yoshizawa M;Doshi P;Jeffery WR
视网膜是眼睛的感光组织，促进视力。影响眼睛发育和视网膜功能的基因突变导致许多退行性视觉疾病，包括视网膜色素变性和眼无/小眼。特征鱼Astyanax mexicanus包括有眼（表面鱼）和无眼（洞穴鱼），它们最初发育成具有正常视网膜的眼睛；然而，在发育的早期，洞穴鱼的眼睛退化了。由于地表和洞穴形态都是同一物种的成员，它们可以作为识别导致视网膜变性的基因的优秀进化突变模型。本研究对115个F2杂交后代进行了有眼与无眼杂交，并对个体视网膜层厚度进行了定量分析。我们利用下一代测序（RAD-seq）和微卫星定位技术构建了Astyanax基因组的密集遗传图谱，扫描影响视网膜厚度的数量性状位点（QTL），并在这些QTL区域内鉴定候选基因。我们为Astyanax构建的图谱包括近700个标记，它们被组合成25个连锁群。根据我们对这张图的扫描，我们确定了四个QTL，每个QTL与视网膜的神经节、内核层、外丛状层和外核层的厚度有关。除了一个QTL外，洞穴鱼等位基因导致受影响层的厚度明显减少。每个QTL内的遗传标记比较作图显示，每个QTL对应于斑马鱼基因组约35mb的区域。在每个区域内，我们确定了与每个受影响视网膜层的功能相关的几个候选基因。我们的研究是第一个在QTL定位的背景下检查Astyanax视网膜变性。我们确定的区域可以作为未来使用进化突变模型Astyanax进行视网膜变性和眼病遗传学研究的起点。
The retina is the light-sensitive tissue of the eye that facilitates vision. Mutations within genes affecting eye development and retinal function cause a host of degenerative visual diseases, including retinitis pigmentosa and anophthalmia/microphthalmia. The characin fish Astyanax mexicanus includes both eyed (surface fish) and eyeless (cavefish) morphs that initially develop eyes with normal retina; however, early in development, the eyes of cavefish degenerate. Since both surface and cave morphs are members of the same species, they serve as excellent evolutionary mutant models with which to identify genes causing retinal degeneration. In this study, we crossed the eyed and eyeless forms of A. mexicanus and quantified the thickness of individual retinal layers among 115 F2 hybrid progeny. We used next generation sequencing (RAD-seq) and microsatellite mapping to construct a dense genetic map of the Astyanax genome, scan for quantitative trait loci (QTL) affecting retinal thickness, and identify candidate genes within these QTL regions. The map we constructed for Astyanax includes nearly 700 markers assembled into 25 linkage groups. Based on our scans with this map, we identified four QTL, one each associated with the thickness of the ganglion, inner nuclear, outer plexiform, and outer nuclear layers of the retina. For all but one QTL, cavefish alleles resulted in a clear reduction in the thickness of the affected layer. Comparative mapping of genetic markers within each QTL revealed that each QTL corresponds to an approximately 35 Mb region of the zebrafish genome. Within each region, we identified several candidate genes associated with the function of each affected retinal layer. Our study is the first to examine Astyanax retinal degeneration in the context of QTL mapping. The regions we identify serve as a starting point for future studies on the genetics of retinal degeneration and eye disease using the evolutionary mutant model Astyanax.
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影响因子：
2.7
作者：
Behesti, Hourinaz;Papaioannou, Virginia E.;Sowden, Jane C.
通讯作者：
Sowden, Jane C.
影响因子：
4.4
作者：
Grossman GH;Pauer GJ;Narendra U;Peachey NS;Hagstrom SA
通讯作者：
Hagstrom SA
DOI：
10.1073/pnas.1130432100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Gibbs, D;Kitamoto, J;Williams, DS
通讯作者：
Williams, DS
影响因子：
3.1
作者：
Borowsky, R;Wilkens, H
通讯作者：
Wilkens, H
影响因子：
2.5
作者：
de Melo, J;Qiu, XG;Eisenstat, DD
通讯作者：
Eisenstat, DD