Related Experiment Video
Updated: Jun 23, 2026
09:16
Array Comparative Genomic Hybridization (Array CGH) for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
Segmental duplications mediate novel, clinically relevant chromosome rearrangements
M Katharine Rudd1, Julia Keene, Brian Bunke
1Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. krudd@genetics.emory.edu
Human Molecular Genetics
|May 16, 2009
Summary
Segmental duplication-mediated genomic rearrangements, including deletions and duplications, are common in patients. Many copy number changes are linked to non-allelic homologous recombination, impacting genomic disorders.
Area of Science:
- Genomics
- Human Genetics
- Molecular Biology
Background:
- Copy number variations (CNVs) are increasingly discovered through segmental duplication-mediated events.
- Clinical array comparative genomic hybridization (aCGH) studies analyze CNVs in patient cohorts.
Purpose of the Study:
- To analyze copy number changes in a large patient cohort.
- To identify and characterize novel loci associated with non-allelic homologous recombination (NAHR).
- To assess the pathogenicity and clinical significance of identified CNVs.
Main Methods:
- Analysis of aCGH data from 2419 patients.
- Identification of CNVs flanked by segmental duplications.
- Characterization of five novel loci with NAHR-mediated gains and losses.
- Evaluation of CNV size, gene content, inheritance patterns, and population data.
Main Results:
- Twenty-three percent of abnormal CNVs were flanked by segmental duplications (>10 kb, >95% identity).
- Five novel loci (2q11.2, 7q36.1, 17q23, 2q13, 7q11.21) with NAHR-mediated CNVs were identified.
- Pathogenic CNVs were identified at 2q11.2, 7q36.1, and 17q23.
- CNVs at 2q13 showed emerging clinical significance, while 7q11.21 deletion was deemed benign.
Conclusions:
- Segmental duplications are key drivers of NAHR-mediated CNVs.
- Specific CNVs have clear pathogenic roles, while others require further investigation.
- Genetic factors influencing phenotypic expression of CNVs are crucial for understanding genomic disorders.
Related Concept Videos
02:37Gene Duplication and Divergence
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
02:08Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
02:05Chromosome Duplication
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
02:04Fixing Double-strand Breaks
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
02:04Polytene Chromosomes
Polytene chromosomes are giant interphase chromosomes with several DNA strands placed side by side. They were discovered in the year 1881 by Balbiani in salivary glands, intestine, muscles, malpighian tubules, and hypoderm of larvae Chironomus plumosus. Hence, these are also called "Salivary gland chromosomes." These are found in insects of the order Diptera and Collembola; in certain organs of mammals; and synergids, antipodes of flowering plants. Polytene chromosomes are also regularly...