Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease

被引：339

作者：

Craven, Lyndsey ^{[2
]}

Tuppen, Helen A. ^{[2
]}

Greggains, Gareth D. ^{[1
,5
]}

Harbottle, Stephen J. ^{[1
]}

Murphy, Julie L. ^{[2
]}

Cree, Lynsey M. ^{[2
]}

Murdoch, Alison P. ^{[1
,4
]}

Chinnery, Patrick F. ^{[2
]}

Taylor, Robert W. ^{[2
]}

Lightowlers, Robert N. ^{[2
]}

Herbert, Mary ^{[1
,4
,5
]}

Turnbull, Douglass M. ^{[2
,3
,4
]}

机构：

[1] Newcastle Univ, Int Ctr Life, Newcastle Fertil Ctr, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England

[2] Newcastle Univ, Inst Ageing & Hlth, Mitochondrial Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[3] Newcastle Univ, Ctr Brain Ageing & Vital, Inst Ageing & Hlth, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[4] Newcastle Univ, Int Ctr Life, Biosci Ctr, NE England Stem Cell Inst NESCI, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England

[5] Newcastle Univ, Int Ctr Life, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 4EP, Tyne & Wear, England

来源：

NATURE | 2010年 / 465卷 / 7294期

基金：

英国工程与自然科学研究理事会; 英国惠康基金; 英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国经济与社会研究理事会;

关键词：

REAL-TIME PCR; 1555A-GREATER-THAN-G MUTATION; PREVALENCE; MOUSE; MTDNA; QUANTIFICATION; SEGREGATION; DISORDERS; DELETIONS; INSIGHTS;

D O I：

10.1038/nature08958

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mutations in mitochondrial DNA ( mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births(1-3) and at least 1 in 10,000 adults in the UK are affected by mtDNA disease(4). Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease(5,6). Here we show that transfer of pronuclei between abnormally fertilized human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure we found the average level of carry-over after transfer of two pronuclei is less than 2.0%, with many of the embryos containing no detectable donor mtDNA. We believe that pronuclear transfer between zygotes, as well as the recently described metaphase II spindle transfer, has the potential to prevent the transmission of mtDNA disease in humans.

引用

页码：82 / U89

页数：6

共 30 条

[1] The effect of temperature fluctuations on the cytoskeletal organisation and chromosomal constitution of the human oocyte [J].