Slightly deleterious genomic variants and transcriptome perturbations in Down syndrome embryonic selection

被引：10

作者：

Popadin, Konstantin ^{[1
,2
,3
,4
]}

Peischl, Stephan ^{[4
,5
]}

Garieri, Marco ^{[1
]}

Sailani, M. Reza ^{[6
]}

Letourneau, Audrey ^{[1
]}

Santoni, Federico ^{[1
]}

Lukowski, Samuel W. ^{[7
]}

Bazykin, Georgii A. ^{[8
,9
]}

Nikolaev, Sergey ^{[1
]}

Meyer, Diogo ^{[10
]}

Excoffier, Laurent ^{[4
,11
]}

Reymond, Alexandre ^{[2
]}

Antonarakis, Stylianos E. ^{[1
]}

机构：

[1] Univ Geneva, Dept Genet Med & Dev, Sch Med, CH-1211 Geneva, Switzerland

[2] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland

[3] Immanuel Kant Baltic Fed Univ, Kaliningrad 236041, Russia

[4] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[5] Univ Bern, Interfac Bioinformat Unit, CH-3012 Bern, Switzerland

[6] Stanford Univ, Stanford Sch Med, Stanford, CA 94305 USA

[7] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia

[8] Russian Acad Sci, Inst Informat Transmiss Problems, Kharkevich Inst, Moscow 127051, Russia

[9] Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Skolkovo 143026, Russia

[10] Univ Sao Paulo, Dept Genet & Evolutionary Biol, BR-05508090 Sao Paulo, Brazil

[11] Univ Bern, Inst Ecol & Evolut, CH-3012 Bern, Switzerland

来源：

GENOME RESEARCH | 2018年 / 28卷 / 01期

基金：

欧洲研究理事会; 瑞士国家科学基金会;

关键词：

GENE-EXPRESSION VARIATION; PROTEIN-CODING GENES; OF-FUNCTION VARIANTS; SEXUAL REPRODUCTION; NEUTRAL THEORY; STEM-CELLS; MUTATIONS; PHENOTYPES; POPULATIONS; FITNESS;

D O I：

10.1101/gr.228411.117

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The majority of aneuploid fetuses are spontaneously miscarried. Nevertheless, some aneuploid individuals survive despite the strong genetic insult. Here, we investigate if the survival probability of aneuploid fetuses is affected by the genome-wide burden of slightly deleterious variants. We analyzed two cohorts of live-born Down syndrome individuals (388 genotyped samples and 16 fibroblast transcriptomes) and observed a deficit of slightly deleterious variants on Chromosome 21 and decreased transcriptome-wide variation in the expression level of highly constrained genes. We interpret these results as signatures of embryonic selection, and propose a genetic handicap model whereby an individual bearing an extremely severe deleterious variant (such as aneuploidy) could escape embryonic lethality if the genome-wide burden of slightly deleterious variants is sufficiently low. This approach can be used to study the composition and effect of the numerous slightly deleterious variants in humans and model organisms.

引用

页码：1 / 10

页数：10

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