Study of structural chromosome abnormalities to increase the understanding of human genetic diversity: a commentary on signature of backward replication slippage at the copy number variation junction

Wakui, Keiko

doi:10.1038/jhg.2014.83

Cited by 1 publication

(1 citation statement)

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“…In addition the testing results of different technical platforms for the inconsistencies in probe design, original data acquisition, and data analysis algorithms can lead to inconsistent results, and use of CMA technology for clinical diagnostics requires corresponding quality requirements [7]. However, most of these problems will be solved in line with the development of concern regarding them [31][32][33].…”

Section: The Establishment Of the Cma Testing Platformmentioning

confidence: 99%

Chromosomal microarray analysis in prenatal diagnosis

Xie¹,

Sun²

2017

Clin. Exp. Obstet. Gynecol.

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Genome copy number variation (CNV) (deletion/duplication) is widely distributed in the whole human genome [1]. It is closely connected with the emergence of new technologies, including high resolution methods of microarray and nextgeneration sequencing. Obviously, large-scale structural changes profoundly influence genetic variation. By various molecular mechanisms, including gene dosage, gene disruption, gene fusion, and position effects, CNVs can cause Mendelian or sporadic traits, or be associated with complex diseases [2,3]. It is also clear that many gene CNVs produce deleterious phenotypic consequences. Particularly, de novo gene CNV is one of the important causes of genetic and developmental disorders including severe mental disabilities, autism, schizophrenia, and heart defects, and is frequently found in cancer cells [2,[4][5][6]. CNV detection methodIn the past 40 years, chromosome analysis using G banding has been considered the gold standard for detection of chromosomal abnormalities. However, this method is time-consuming, requires cell culture, has limited resolution, and is not sufficient for the detection of less than five MB of chromosomal abnormalities. To further identify changes less than five MB in size, a combination of genetics and molecular biology methods was developed. Fluorescence in situ hybridisation technique (FISH) and multiplex ligation-dependent probe amplification (MLPA) can detect chromosome imbalances smaller than one MB, but these techniques can only be used in a limited area of chromosomal abnormalities, and a pre-test must be expected for the detection of disease and targeted. In prenatal diagnosis, chromosomal microarray analysis (CMA) can detect genome level abnormalities, and no cell culture is required, thus shortening the time that patients await results that can be used for the detection of fetal death or stillbirth. Additionally, CMA is a standardised process that utilises computer analysis, whereas karyotyping requires microscopic examination of chromosomes after staining. Karyotype analysis may be more subjective and prone to human error.CMA technology, also known as molecular karyotype analysis technique (molecular karyotyping), is based on microarray genome copy number analysis technologies including comparative genomic hybridisation array (aCGH) technology and single nucleotide polymorphism microarray (SNP array) technology. CMA can detect unbalanced chromosome CNV at the entire genome level and can be used to identify chromosomal abnormalities, including those that are too small to detect by conventional karyotype analysis, tiny chromosomal abnormalities. The probe design, the original data acquisition, the data analysis algorithms, and other factors are the key causes to inconsistent results, and the CMA detection technology in clinical diagnostics using quality requirements are presented here along with the corresponding goals [7]. CMA clinical application of the status quoCMA is currently the most effective tool to evaluate copy number abnormalities, which ar...

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