Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: McCoy, Rajiv C; Demko, Zachary; Ryan, Allison; Banjevic, Milena; Hill, Matthew; Sigurjonsson, Styrmir; Rabinowitz, Matthew; Fraser, Hunter B; Petrov, Dmitri A
Year of Publication: 2015
Journal: Science
Volume: 348
Issue: 6231
Pagination: 235-8
Date Published: 2015 Apr 10
Publication Language: eng
ISSN: 1095-9203
Keywords: Alleles, Aneuploidy, Blastomeres, Embryo, Mammalian, 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, Selection, Genetic, Trophoblasts

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.

DOI: 10.1126/science.aaa3337
Alternate Journal: Science