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Published on: July 25, 2020
Genomic analysis using high-resolution single-nucleotide polymorphism arrays reveals novel microdeletions associated
Megan M McGuire1, Wayne Bowden, Natalie J Engel
1Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Objective:
To analyze DNA from women with premature ovarian failure (POF) for genome-wide copy-number variations (CNVs), focusing on novel autosomal microdeletions.
Design:
Case-control genetic association study.
Setting:
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
Patient(S):
Of 89 POF patients, eight experienced primary amenorrhea and 81 exhibited secondary amenorrhea before age 40 years.
Intervention(S):
Genomic DNA from peripheral blood samples was analyzed for CNVs using high-resolution single-nucleotide polymorphism (SNP) arrays.
Main Outcome Measure(S):
Identification of novel CNVs in 89 POF cases, using the Database of Genomic Variants as a control population.
Result(S):
A total of 198 autosomal CNVs were detected by SNP arrays, ranging in size from 0.1 Mb to 3.4 Mb. These CNVs (>0.1 Mb) included 17 novel microduplications and seven novel microdeletions, six of which contained the coding regions 8q24.13, 10p15-p14, 10q23.31, 10q26.3, 15q25.2, and 18q21.32. Most of the novel CNVs were derived from autosomes rather than the X chromosome.
Conclusion(S):
The present pilot study revealed novel microdeletions/microduplications in women with POF. Two novel microdeletions caused haploinsufficiency for SYCE1 and CPEB1, genes known to cause ovarian failure in knockout mouse models. Chromosomal microarrays may be a useful adjunct to conventional karyotyping when evaluating genomic imbalances in women with POF.
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Single Nucleotide Polymorphisms-SNPs
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