Subchromosomal abnormalities can be positioned by the detection of copy number variation (CNV) using microarray comparative genomic hybridization (aCGH). aCGH has become a powerful tool in understanding the association between gene and genetic etiology in both research and clinical laboratories. Meanwhile as a new technique, controversies inevitably arose in its clinical application. As for the phenotype of CNV, little has been disclosed. For the clinicians, the difficulty in explanation of the CNV to the patients is obvious, which makes many doctors refuse to use aCGH for clinical diagnosis. Customized arrays have been exploited to decrease the uncertainty and efforts to search for a balance between overloaded information and insufficient information have been made. The purpose of this review is to discuss the current limitations and difficulties in application of aCGH in prenatal diagnosis and its application prospect from the point of a clinician.
Comparative Genomic Hybridization ; methods ; DNA Copy Number Variations ; Female ; Humans ; Oligonucleotide Array Sequence Analysis ; methods ; Pregnancy ; Prenatal Diagnosis ; methods

OBJECTIVETo assess the value of spectral karyotyping (SKY) combined with microarray-based comparative genomic hybridization (array-CGH) for the diagnosis of complex ring chromosome aberration.

METHODSFor an 8-year-old boy featuring growth retardation, G-banding analysis has indicated a 46,XY,r(15)? karyotype, which was delineated by SKY in combination with array-CGH.

RESULTSThe ring chromosome has originated from chromosome 15 according to SKY analysis. Position of the breakpoint (15q26.3) and a 594 kb deletion were revealed by array-CGH.

CONCLUSIONMolecular cytogenetic technologies are efficient tools for clarifying complex chromosomal abnormality, which has provided a powerful tool for conventional cytogenetic analysis.

Child ; Chromosomes, Human, Pair 15 ; Comparative Genomic Hybridization ; methods ; Humans ; Male ; Mosaicism ; Oligonucleotide Array Sequence Analysis ; Ring Chromosomes ; Spectral Karyotyping

OBJECTIVETo establish an assay for screening chromosome 22q11 microdeletion efficiently, and apply it for detecting del22q11 in patients with non-syndromic congenital heart defects (CHD).

METHODSSeventy nine patients with non-syndromic CHD and 84 normal controls were genotyped for 8 short tandem repeat (STR) markers located in 22q11 region, by using quantitative fluorescence polymerase chain reaction (QF-PCR).

RESULTSThe average heterozygosity of the STR markers in patients and controls was 0.76 and 0.79, respectively. One patient with Tetralogy of Fallot (TOF) from the 79 CHD cases (1.3%) was found to have a deletion within chromosome 22q11.2, which was confirmed by multiplex ligation-dependent probe amplification (MLPA).

CONCLUSIONThe QF-PCR assay developed in this study was a reliable and an efficient alterative approach to screen for 22q11 microdeletion in clinical diagnosis and genetic counseling.

Case-Control Studies ; Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; Fluorescence ; Heart Defects, Congenital ; diagnosis ; genetics ; Humans ; Microsatellite Repeats ; Polymerase Chain Reaction ; instrumentation ; methods

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1% of azoospermia or severe oligospermia. However, the underlying mechanisms of pathogenesis and etiologies are still largely unknown. Herein, we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants. In addition, high read-depth genome sequencing (GS) (30-fold) was performed to investigate point mutations causative of male infertility. Mate-pair GS (4-fold) revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements. Overall, the breakpoints caused truncations of 30 RefSeq genes, five of which were associated with spermatogenesis. Furthermore, the breakpoints disrupted 43 topological-associated domains. Direct disruptions or potential dysregulations of genes, which play potential roles in male germ cell development, apoptosis, and spermatogenesis, were found in all cases (n = 6). In addition, high read-depth GS detected dual molecular findings in case MI6, involving a complex rearrangement and two point mutations in the gene DNAH1. Overall, our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility. We demonstrated the complexity of chromosomal structural rearrangements, potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.
Azoospermia/genetics* ; Chromosome Aberrations ; Humans ; Infertility, Male/genetics* ; Male ; Oligospermia/genetics* ; Translocation, Genetic