Clinical utilization of chromosomal microarray analysis for the genetic analysis in subgroups of pregnancy loss

Gou, Lingshan; Liu, Tianya; Wang, Yi; Wu, Qingqing; Hu, Shunan; Dong, Bulian; Wang, Chuanxia; Zhang, Yan; Shan, Xinghu; Wang, Xiaona; Feng, Shi Ting; Gu, Maosheng

doi:10.1080/14767058.2020.1849126

Cited by 8 publications

(15 citation statements)

References 34 publications

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“…Our result supported the research findings that trisomic risk was increased with maternal age while monosomy X decreased with maternal age (Gu et al, 2021;Gug et al, 2019;Kajii & Ohama, 1979;Warburton et al, 1980;Zhang, Fan, et al, 2021). The relationship between history of adverse pregnancy and chromosomal abnormality was still controversial (Chen et al, 2021;Gou et al, 2022;Ozawa et al, 2019;Wang et al, 2017;Zhang, Fan, et al, 2021), our result provided more support that number of miscarriages was irrelevant to chromosomal aberrations. In the logistic regression, although gestational age was the only significant associated factor, our result showed a trend that women with advanced age, first-time abortion, and abortion earlier than 12 weeks were more likely to detect chromosomal abnormalities in their fetal tissues.…”

Section: Discussionsupporting

confidence: 89%

Sequential application of copy number variation sequencing and quantitative fluorescence polymerase chain reaction in genetic analysis of miscarriage and stillbirth

Chen

Zhang

et al. 2023

Molec Gen & Gen Med

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BackgroundCopy number variation sequencing (CNV‐seq) could detect most chromosomal abnormalities except polyploidy, and quantitative fluorescence polymerase chain reaction (QF‐PCR) is a supplementary method to CNV‐seq in triploid detection. This study aimed to evaluate the feasibility of sequential application of CNV‐seq and QF‐PCR in genetic analysis of miscarriage and stillbirth.MethodsA total of 261 fetal specimens were analyzed by CNV‐seq, and QF‐PCR was only further performed for samples with normal female karyotype identified by CNV‐seq. Cost and turnaround time (TAT) was analyzed for sequential detection strategy. Subgroup analysis and logistic regression were carried out to evaluate the relationship between clinical characteristics (maternal age, gestational age, and number of pregnancy losses) and the occurrence of chromosomal abnormalities.ResultsAbnormal results were obtained in 120 of 261 (45.98%) cases. Aneuploidy was the most common abnormality (37.55%), followed by triploidy (4.98%) and pathogenic copy number variations (pCNVs) (3.45%). CNV‐seq could detect the triploidy with male karyotype, and QF‐PCR could further identify the remaining triploidy with female karyotype. In this study, we found more male triploidies than female triploidies. With the same ability in chromosomal abnormalities detection, the cost of sequential strategy decreased by 17.35% compared with combined strategy. In subgroup analysis, significant difference was found in the frequency of total chromosomal abnormalities between early abortion group and late abortion group. Results of logistic regression showed a trend that pregnant women with advanced age, first‐time abortion, and abortion earlier than 12 weeks were more likely to detect chromosomal aberrations in their products of conception.ConclusionSequential application of CNV‐seq and QF‐PCR is an economic and practical strategy to identify chromosomal abnormalities in fetal tissue.

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Section: Discussionsupporting

confidence: 89%

Sequential application of copy number variation sequencing and quantitative fluorescence polymerase chain reaction in genetic analysis of miscarriage and stillbirth

Chen

Zhang

et al. 2023

Molec Gen & Gen Med

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“…For nearly two decades, microarray analysis has been used to identify genomic gains and losses associated with chromosomal anomalies in humans, including autosomal and sex chromosome aneuploidies (Shaffer and Bejjani, 2004;Ballif et al 2006;Shaffer et al 2012; Shaffer & Rosenfeld 2013; Gou et al 2020). SNP array analysis, in particular, is a powerful way to directly assess individual genotypes in known disease loci while allowing for identi cation of copy number gains and losses representing aneuploidy, aneusomy and mosaicism (Conlin et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Identification of aneuploidy in dogs screened by a SNP microarray

Shaffer

Hopp²,

Świtoński

et al. 2021

Hum Genet

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Microarray analysis is an e cient approach for screening and identifying cytogenetic imbalances in humans. SNP arrays, in particular, are a powerful way to identify copy number gains and losses representing aneuploidy and aneusomy, but moreover, allow for the direct assessment of individual genotypes in known disease loci. Using these approaches, trisomies, monosomies and mosaicism of whole chromosomes have been identi ed in human microarray studies. For canines, this approach is not widely used in clinical laboratory diagnostic practice. In our laboratory, we have implemented the use of a propriety SNP array that represents approximately 650,000 loci across the domestic dog genome. During the validation of this microarray prior to clinical use, we identi ed three cases of aneuploidy after screening 2,053 dogs of various breeds including monosomy X, trisomy X and an apparent, mosaic trisomy of canine chromosome 38 (CFA 38). This study represents the rst use of microarrays for copy number evaluation to identify cytogenetic anomalies in canines. As microarray analysis becomes more routine in canine genetic testing, more cases of chromosome aneuploidy are likely to be uncovered.

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“…Some disadvantages of the QF-PCR and MLPA methods used in present study include the inability to detect balanced structural chromosomal rearrangements, as well as inter-stitial deletions and duplications, ring chromosomes, and inversions. Some of these variations could be detected with other molecular approaches such as aCGH and NGS-based methodologies, but because of their higher price, they are not widely used in the investigation of EPLs samples [ 5 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…The aetiology of EPL can include various factors, such as maternal endocrine dysregulation, anatomical abnormalities of the uterus, implantation factors, various infections during the pregnancy and foetal chromosomal abnormalities. About 40–65% of the miscarried foetuses are associated with various chromosomal abnormalities, the most common of which are chromosomal trisomies, followed by polyploidies and monosomy X [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Chromosomal Abnormalities in Early Pregnancy Losses: A Study of 900 Samples

Bozhinovski,

Terzikj,

Kubelka-Sabit

et al. 2023

Balkan Journal of Medical Genetics

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Chromosomal abnormalities are the most common causes of early pregnancy losses (EPLs). In this study, we aimed to evaluate the incidence and spectrum of chromosomal abnormalities in EPLs and correlate them with different clinical characteristics. We performed Quantitative Fluorescent PCR (QF-PCR), followed by subtelomeric Multiplex Ligation Probe Amplification (MLPA) analysis to detect chromosomal abnormalities in 900 products of conceptions (POCs) from EPLs collected over a period of 10 years. Chromosomal abnormalities were present in 56.25% of uncontaminated EPLs, with significantly higher incidence in women ≥36 years (71.37%, p<0.0001) in comparison to women ≤30 years of age (43.40%). Trisomies were also more common in women ≥36 years (79.68%, p<0.0001) than in those ≤30 years of age (48.70%). In contrast, triploidy and monosomies were more prevalent in women ≤30 years of age (26.09%, p<0.0001 and 16.52%, p=0.0066 respectively) than in women ≥36 years of age (6.42% and 6.42% respectively). Trisomy 16 was more common in women ≤30 (39.29%, p=0.0009) than in those ≥36 years of age (16.78%), while trisomy 22 was predominant among women ≥36 (23.49%, p=0.013), and was not present in the group of women ≤30 years of age. The frequency of chromosomal abnormalities in POCs from women with sporadic (61.19%) was higher than in those with recurrent EPLs (55.21%). This difference, however, was not statistically significant (p=0.164). Although some differences in the chromosomal aneuploidy rates among women with different ABO blood groups, as well as among 6–8 and 9–11 gestational week EPLs were observed, further larger studies are required to confirm these findings. In conclusion, our study enriches the knowledge about chromosomal abnormalities as a cause of EPLs and confirms the higher incidence of foetal chromosomal abnormalities in EPLs in women of older reproductive age. Furthermore, it shows that using QF-PCR and MLPA methodologies, a high detection rate of chromosomal abnormalities in EPLs can be reached.

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Clinical utilization of chromosomal microarray analysis for the genetic analysis in subgroups of pregnancy loss

Cited by 8 publications

References 34 publications

Sequential application of copy number variation sequencing and quantitative fluorescence polymerase chain reaction in genetic analysis of miscarriage and stillbirth

Sequential application of copy number variation sequencing and quantitative fluorescence polymerase chain reaction in genetic analysis of miscarriage and stillbirth

Identification of aneuploidy in dogs screened by a SNP microarray

Chromosomal Abnormalities in Early Pregnancy Losses: A Study of 900 Samples

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