新浪登录
腾讯登录Sci Transl Med：对人类胎儿的整个基因组测序
| 导读 | <div id="region-column1and2-layout2">
<div>近日，刊登在国际著名杂志<em>Science Translational Medicine</em>上的一篇文章中，研究人员指出，他们已经用从一名孕妇及一个即将成为父亲的人身上获取的DNA样本重构了一个人类胎儿的全部基因组序列。</di... |
<div id="region-column1and2-layout2">
<div>近日，刊登在国际著名杂志<em>Science Translational Medicine</em>上的一篇文章中，研究人员指出，他们已经用从一名孕妇及一个即将成为父亲的人身上获取的DNA样本重构了一个人类胎儿的全部基因组序列。</div>
</div>
<div id="region-column1and2-layout2">
这些发现开启了用一种非侵入性测试来对某胎儿的所有单基因疾病或“孟德尔”病进行产前评估的可能性，而这种测试可替换像羊膜穿刺术及绒毛膜取样等侵入性的手术。有超过3000种孟德尔病会共同影响约1%的新生儿。这些疾病中的大多数是由小型的、难以发现的基因变异引起的。Jacob Kitzman及其同事使用了最先进的技术在第二孕期中来确定人类胎儿的全部基因组序列。有两种类型的基因变异：遗传性突变及全新的基因突变。
<!--more-->
一个母亲的基因组中含有数百万个遗传变异株，它们在她的部分基因组中被组合在了一起，她的基因组是从其父母那里遗传来的。这些变异株群被称作“单倍体型”。本文作者使用的方法可发现单倍体型在每个染色体上是如何组成的，并根据这一信息发现胎儿从其母亲那里遗传的变异体。新的变异可通过对来自母血中的血浆DNA的信息进行计算分析而发现。尽管该技术需要改进，但这项研究暗示，对孟德尔病进行非侵入、综合性的产前筛检可能在不远的将来变得可行。
<img src="http://www.bioon.com/biology/UploadFiles/201206/2012060709535880.jpg" alt="" width="113" height="149" border="0" />
<div id="ztload">
<div>
<div>
<a title="" href="http://dx.doi.org/doi:10.1126/scitranslmed.3004323" target="_blank">doi:10.1126/scitranslmed.30043232</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Noninvasive Whole-Genome Sequencing of a Human Fetus</strong><br/>
Jacob O. Kitzman1,*, Matthew W. Snyder1, Mario Ventura1,2, Alexandra P. Lewis1, Ruolan Qiu1, LaVone E. Simmons3, Hilary S. Gammill3,4, Craig E. Rubens5,6, Donna A. Santillan7, Jeffrey C. Murray8, Holly K. Tabor5,9, Michael J. Bamshad1,5, Evan E. Eichler1,10 and Jay Shendure1,*
Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 × 106 parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo point mutations in the fetal genome were detected, albeit with limited specificity. Subsampling these data and analyzing a second family trio by the same approach indicate that parental haplotype blocks of ~300 kilo–base pairs combined with shallow sequencing of maternal plasma DNA is sufficient to substantially determine the inherited complement of a fetal genome. However, ultradeep sequencing of maternal plasma DNA is necessary for the practical detection of fetal de novo mutations genome-wide. Although technical and analytical challenges remain, we anticipate that noninvasive analysis of inherited variation and de novo mutations in fetal genomes will facilitate prenatal diagnosis of both recessive and dominant Mendelian disorders.
<div id="region-column1and2-layout2">
<div><br/>来源：EurekAlert!</div>
</div>
</div>
</div>
</div>
</div>
<div>近日，刊登在国际著名杂志<em>Science Translational Medicine</em>上的一篇文章中，研究人员指出，他们已经用从一名孕妇及一个即将成为父亲的人身上获取的DNA样本重构了一个人类胎儿的全部基因组序列。</div>
</div>
<div id="region-column1and2-layout2">
这些发现开启了用一种非侵入性测试来对某胎儿的所有单基因疾病或“孟德尔”病进行产前评估的可能性，而这种测试可替换像羊膜穿刺术及绒毛膜取样等侵入性的手术。有超过3000种孟德尔病会共同影响约1%的新生儿。这些疾病中的大多数是由小型的、难以发现的基因变异引起的。Jacob Kitzman及其同事使用了最先进的技术在第二孕期中来确定人类胎儿的全部基因组序列。有两种类型的基因变异：遗传性突变及全新的基因突变。
<!--more-->
一个母亲的基因组中含有数百万个遗传变异株，它们在她的部分基因组中被组合在了一起，她的基因组是从其父母那里遗传来的。这些变异株群被称作“单倍体型”。本文作者使用的方法可发现单倍体型在每个染色体上是如何组成的，并根据这一信息发现胎儿从其母亲那里遗传的变异体。新的变异可通过对来自母血中的血浆DNA的信息进行计算分析而发现。尽管该技术需要改进，但这项研究暗示，对孟德尔病进行非侵入、综合性的产前筛检可能在不远的将来变得可行。
<img src="http://www.bioon.com/biology/UploadFiles/201206/2012060709535880.jpg" alt="" width="113" height="149" border="0" />
<div id="ztload">
<div>
<div>
<a title="" href="http://dx.doi.org/doi:10.1126/scitranslmed.3004323" target="_blank">doi:10.1126/scitranslmed.30043232</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Noninvasive Whole-Genome Sequencing of a Human Fetus</strong><br/>
Jacob O. Kitzman1,*, Matthew W. Snyder1, Mario Ventura1,2, Alexandra P. Lewis1, Ruolan Qiu1, LaVone E. Simmons3, Hilary S. Gammill3,4, Craig E. Rubens5,6, Donna A. Santillan7, Jeffrey C. Murray8, Holly K. Tabor5,9, Michael J. Bamshad1,5, Evan E. Eichler1,10 and Jay Shendure1,*
Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 × 106 parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo point mutations in the fetal genome were detected, albeit with limited specificity. Subsampling these data and analyzing a second family trio by the same approach indicate that parental haplotype blocks of ~300 kilo–base pairs combined with shallow sequencing of maternal plasma DNA is sufficient to substantially determine the inherited complement of a fetal genome. However, ultradeep sequencing of maternal plasma DNA is necessary for the practical detection of fetal de novo mutations genome-wide. Although technical and analytical challenges remain, we anticipate that noninvasive analysis of inherited variation and de novo mutations in fetal genomes will facilitate prenatal diagnosis of both recessive and dominant Mendelian disorders.
<div id="region-column1and2-layout2">
<div><br/>来源：EurekAlert!</div>
</div>
</div>
</div>
</div>
</div>
还没有人评论，赶快抢个沙发