Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia.

نویسندگان

  • Daryl A Scott
  • Merel Klaassens
  • Ashley M Holder
  • Kevin P Lally
  • Caraciolo J Fernandes
  • Robert-Jan Galjaard
  • Dick Tibboel
  • Annelies de Klein
  • Brendan Lee
چکیده

Non-isolated congenital diaphragmatic hernia (CDH+) is a severe birth defect that is often caused by de novo chromosomal anomalies. In this report, we use genome-wide oligonucleotide-based array comparative genome hybridization (aCGH) followed by rapid real-time quantitative PCR analysis to identify, confirm and map chromosomal anomalies in a cohort of 26 CDH+ patients. One hundred and five putative copy number changes were identified by aCGH in our cohort of CDH+ patients. Sixty-one of these changes (58%) had been previously described in normal controls. Twenty of the remaining 44 changes (45%) were confirmed by quantitative real-time PCR or standard cytogenetic techniques. These changes included de novo chromosomal abnormalities in five of the 26 patients (19%), two of whom had previously normal G-banded chromosome analyses. Data from these patients provide evidence for the existence of CDH-related genes on chromosomes 2q37, 6p22-25 and 14q, and refine the CDH minimal deleted region on 15q26 to an interval that contains COUP-TFII and only eight other known genes. Although COUP-TFII is likely to play a role in the development of CDH in patients with 15q26 deletions, we did not find COUP-TFII mutations in 73 CDH samples. We conclude that the combination of oligonucleotide-based aCGH and quantitative real-time PCR is an effective method of identifying, confirming and mapping clinically relevant copy number changes in patients with CDH+. This method is more sensitive than G-banded chromosome analysis and may find wide application in screening patients with congenital anomalies.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Copy number imbalances detected with a BAC-based array comparative genomic hybridization platform in congenital diaphragmatic hernia fetuses.

Congenital diaphragmatic hernia (CDH) is a phenotypically and genetically heterogeneous disorder, with a complex inheritance pattern. Structural abnormalities of almost all chromosomes have been described in association with CDH. We made a molecular analysis through array comparative genomic hybridization (array CGH) of a group of fetuses with prenatal ultrasound diagnosis of CDH and normal G-b...

متن کامل

A Comparative Analysis between Right and Left Congenital Diaphragmatic Hernias

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly of the diaphragm with an incidence of 1:2000-5000 of live births. This study retrospectively evaluated patients who had been operated on for CDH at our department of Pediatric Surgery between January 2013 and December 2016. The Demographic Data and outcomes of right CDH cases (Group 1) were compared with left CDH cases (Group 2).

متن کامل

Analysis of chromosomal aberrations in patients with mental retardation using the array-CGH technique: a single Czech centre experience.

Submicroscopic structural chromosomal aberrations (microduplications and microdeletions) are believed to be common causes of mental retardation. These so-called copy number variations can now be routinely detected using various platforms for array-based comparative genomic hybridization (array-CGH), which allow genome-wide identification of pathogenic genomic imbalances. In this study, oligonuc...

متن کامل

A Robust Whole Genome Amplification Method for Agilent Array-based Comparative Genome Hybridization Analysis

Genomic instability is a classic hallmark of cancer and genetic disorders. The Agilent Oligonucleotide array-based Comparative Genomic Hybridization (aCGH) platform lets you profile DNA copy number variations on a highthroughput and genome-wide scale. We have developed a rapid, low-input whole genome amplification (WGA) method for aCGH analysis that pairs the Sigma GenomePlex WGA Kit with Agile...

متن کامل

Mapping candidate regions and genes for congenital anomalies of the kidneys and urinary tract (CAKUT) by array-based comparative genomic hybridization.

BACKGROUND Congenital anomalies of the kidneys and urinary tract (CAKUT) are frequently associated with malformations of other organs. METHODS In order to explore the role of DNA microimbalances in syndromal CAKUT, we applied genome-wide array-based comparative genomic hybridization (array-CGH) in 30 children with various CAKUT phenotypes and at least one additional extrarenal symptom. RESU...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Human molecular genetics

دوره 16 4  شماره 

صفحات  -

تاریخ انتشار 2007