近日，刊登在國(guó)際著名雜志Science Translational Medicine上的一篇文章中,，研究人員指出,，他們已經(jīng)用從一名孕婦及一個(gè)即將成為父親的人身上獲取的DNA樣本重構(gòu)了一個(gè)人類胎兒的全部基因組序列。
這些發(fā)現(xiàn)開(kāi)啟了用一種非侵入性測(cè)試來(lái)對(duì)某胎兒的所有單基因疾病或“孟德?tīng)?rdquo;病進(jìn)行產(chǎn)前評(píng)估的可能性,，而這種測(cè)試可替換像羊膜穿刺術(shù)及絨毛膜取樣等侵入性的手術(shù),。有超過(guò)3000種孟德?tīng)柌?huì)共同影響約1%的新生兒。這些疾病中的大多數(shù)是由小型的,、難以發(fā)現(xiàn)的基因變異引起的,。Jacob Kitzman及其同事使用了最先進(jìn)的技術(shù)在第二孕期中來(lái)確定人類胎兒的全部基因組序列。有兩種類型的基因變異：遺傳性突變及全新的基因突變,。
一個(gè)母親的基因組中含有數(shù)百萬(wàn)個(gè)遺傳變異株,，它們?cè)谒牟糠只蚪M中被組合在了一起，她的基因組是從其父母那里遺傳來(lái)的,。這些變異株群被稱作“單倍體型”,。本文作者使用的方法可發(fā)現(xiàn)單倍體型在每個(gè)染色體上是如何組成的，并根據(jù)這一信息發(fā)現(xiàn)胎兒從其母親那里遺傳的變異體,。新的變異可通過(guò)對(duì)來(lái)自母血中的血漿DNA的信息進(jìn)行計(jì)算分析而發(fā)現(xiàn),。盡管該技術(shù)需要改進(jìn)，但這項(xiàng)研究暗示,，對(duì)孟德?tīng)柌∵M(jìn)行非侵入,、綜合性的產(chǎn)前篩檢可能在不遠(yuǎn)的將來(lái)變得可行。（生物谷Bioon.com）
doi:10.1126/scitranslmed.30043232
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Noninvasive Whole-Genome Sequencing of a Human Fetus
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.
