Abstract
Objective
Chromosome aberrations are generally considered as one of the most substantial causative
factors contributing to spontaneous miscarriages. Cytogenetic analyses like G-banded
karyotype and chromosomal microarray analyses are often performed to further investigate
the chromosome status of a miscarried fetus.
Study design
Here, we describe a novel method, AnnoCNV, to detect DNA copy number variations (CNVs)
using low coverage whole genome sequencing (WGS). We investigated the overall frequency
of chromosomal abnormalities in 149 miscarriage specimens using AnnoCNV.
Results
Among 149 fetal miscarriage samples, more than two fifths of them (42.95%, 64) carried
at least one chromosomal abnormality, and a subset (40) was identified as autosomal
trisomy which account for 26.84% of all samples. We have also developed a robust algorithm
in AnnoCNV, which is able to differentiate specifically karyotype 69,XXY from sex
chromosomal aneuploidy 45,X, and to identify 45,X/46,XX mosaicism. Lastly, across
the whole genome AnnoCNV identifies CNVs, which are associated with both reported
symptoms and unknown clinical conditions.
Conclusion
This cost-effective strategy reveals genome wide discovery of chromosome aberrations
at higher resolution, which are consistent with parallel investigation conducted by
SNP based assay.
Abbreviations:
CNV (copy number variation), WGS (whole genome sequencing), CMA (chromosomal microarray analysis), NGS (next-generation sequencing), NKD (normal-karyotype database), DGV (database of genomic variants), OMIM (Online Mendelian Inheritance in Man)Keywords
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References
- A cytogenetic study of 1000 spontaneous abortions.Ann Hum Genet. 1980; 44: 151-164
- Early risk factors for miscarriage: a prospective cohort study in pregnant women.Reprod Biomed Online. 2016; 17: 101-113
- Recurrent miscarriage.N Engl J Med. 2010; 363: 1740-1747
- Structural genomic variation as risk factor for idiopathic recurrent miscarriage.Hum Mutat. 2014; 35: 972-982
- Chromosomal abnormalities in couples with reproductive disorders.Gynecol Obstet Invest. 2008; 66: 237-240
- Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy.Hum Genet. 1985; 70: 11-17
- 4 the origin of numerical chromosome abnormalities.in: Advances in genetics. vol. 33. Academic Press, 1995: 101-133
- Mosaic aneuploidy in early fetal losses.Cytogenet Genome Res. 2011; 133: 169-183
- Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions.Am J Hum Genet. 2000; 66: 1516-1521
- High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays.Nat Genet. 1998; 20: 207-211
- Assembly of microarrays for genome-wide measurement of DNA copy number.Nat Genet. 2001; 29: 263-264
- Development and validation of an accurate quantitative real-time polymerase chain reaction-based assay for human blastocyst comprehensive chromosomal aneuploidy screening.Fertil Steril. 2012; 97 (e812): 819-824
- 24-chromosome copy number analysis: a comparison of available technologies.Fertil Steril. 2013; 100: 595-602
- Massively parallel sequencing for chromosomal abnormality testing in trophectoderm cells of human blastocysts.Biol Reprod. 2013; 88: 69
- Low-pass whole-genome sequencing in clinical cytogenetics: a validated approach.Genet Med. 2016; 18: 940-948
- Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing.Prenat Diagn. 2013; 33: 409-415
- Noninvasive prenatal testing of fetal aneuploidies by massively parallel sequencing in a prospective Chinese population.Prenat Diagn. 2013; 33: 700-706
- Fast and accurate short read alignment with Burrows–Wheeler transform.Bioinformatics. 2009; 25: 1754-1760
- The Database of Genomic Variants: a curated collection of structural variation in the human genome.Nucleic Acids Res. 2014; 42: D986-D992
- Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.Nucleic Acids Res. 2005; 33: D514-D517
- Comparative genomic hybridization-Array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages.Am J Hum Genet. 2004; 74: 1168-1174
- Traditional karyotyping vs copy number variation sequencing for detection of chromosomal abnormalities associated with spontaneous miscarriage.Ultrasound Obstet Gynecol. 2015; 46: 472-477
- Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis.Hum Mol Genet. 2010; 19: 1263-1275
- Mosaic uniparental disomies and aneuploidies as large structural variants of the human genome.Am J Hum Genet. 2010; 87: 129-138
- Exclusion of chromosomal mosaicism: tables of 90%, 95% and 99% confidence limits and comments on use.Am J Hum Genet. 1977; 29: 94-97
- Copy number variants, diseases and gene expression.Hum Mol Genet. 2009; 18: R1-R8
- Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology.Expert Rev Mol Med. 2005; 7: 1-20
- Prader-Willi syndrome.J Med Genet. 1997; 34: 917-923
- Prader–Willi syndrome.Eur J Hum Genet. 2009; 17: 3-13
- Mammalian nicotinic acetylcholine receptors: from structure to function.Physiol Rev. 2009; 89: 73-120
- Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility.Am J Med Genet A. 2015; 167: 715-723
- Trisomy 16 and trisomy 16 mosaicism: a review.Am J Med Genet. 1998; 79: 121-133
- The sequence and analysis of duplication-rich human chromosome 16.Nature. 2004; 432: 988-994
- Gene expression profiling in the adult Down syndrome brain.Genomics. 2007; 90: 647-660
- Massive-Scale RNA-Seq analysis of non ribosomal transcriptome in human trisomy 21.PLoS One. 2011; 6: e18493
- Domains of genome-wide gene expression dysregulation in Down’s syndrome.Nature. 2014; 508: 345-350
- Identification of recurrent focal copy number variations and their putative targeted driver genes in ovarian cancer.BMC Bioinformatics. 2016; 17: 222
- Genomic characteristics of miscarriage copy number variants.Mol Hum Reprod. 2015; 21: 655-661
- Genomic rearrangements and sporadic disease.Nat Genet. 2007; 39: S43-S47
- Trisomy 16 detected by first trimester screening.Prenat. Diagn. 2009; 29: 1175-1176https://doi.org/10.1002/pd.2369
- An audit of trisomy 16 in man.Prenat. Diagn. 1995; 15: 109-121https://doi.org/10.1002/pd.1970150202
Article info
Publication history
Published online: March 08, 2018
Accepted:
March 4,
2018
Received in revised form:
February 22,
2018
Received:
April 20,
2017
Identification
Copyright
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