Publication Date:
2015-04-11
Description:
Aneuploidy, the inheritance of an atypical chromosome complement, is common in early human development and is the primary cause of pregnancy loss. By screening day-3 embryos during in vitro fertilization cycles, we identified an association between aneuploidy of putative mitotic origin and linked genetic variants on chromosome 4 of maternal genomes. This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon minor dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for testing at day 5, suggesting that their embryos are less likely to survive to blastocyst formation. The associated region coincides with a signature of a selective sweep in ancient humans, suggesting that the causal variant was either the target of selection or hitchhiked to substantial frequency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCoy, Rajiv C -- Demko, Zachary -- Ryan, Allison -- Banjevic, Milena -- Hill, Matthew -- Sigurjonsson, Styrmir -- Rabinowitz, Matthew -- Fraser, Hunter B -- Petrov, Dmitri A -- R01 GM089926/GM/NIGMS NIH HHS/ -- R01 GM097415/GM/NIGMS NIH HHS/ -- R01 GM100366/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 10;348(6231):235-8. doi: 10.1126/science.aaa3337.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Stanford University, Stanford, CA, USA. ; Natera, Inc., San Carlos, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25859044" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
*Aneuploidy
;
Blastomeres
;
Embryo, Mammalian/*physiology
;
Embryonic Development
;
Fathers
;
Female
;
Fertilization in Vitro
;
Genetic Association Studies
;
Genetic Testing
;
Haplotypes
;
Humans
;
Male
;
*Mitosis
;
Mothers
;
Phenotype
;
*Polymorphism, Single Nucleotide
;
Protein-Serine-Threonine Kinases/*genetics/physiology
;
Selection, Genetic
;
Trophoblasts
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
