Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions

Raihan K Uddin,Jay Rao,Richard L O'Reilly,Yao-Shan Fan,Yang Zhang,Shiva M Singh,Victoria Mok Siu

doi:10.1186/1471-2350-7-18

Abstract

BackgroundChromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia.MethodsGenotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient.ResultsThis 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements.ConclusionThis Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion.

Highlights

Chromosome 22q11.2 region is highly susceptible to rearrangement, deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome
This analysis enabled us to narrow down the deletion breakpoint regions while PCR amplification of the recombined DNA and its sequencing allowed us to establish the sequence of the patient specific deleted region
Origin and mechanism of the 2.3 Mb 22q11 deletion We propose that the mechanism of this novel deletion is not any different from other deletions of this region, even though its distal breakpoint was not contained in an low copy repeat regions (LCRs) area

Summary

Introduction

Chromosome 22q11.2 region is highly susceptible to rearrangement, deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. BMC Medical Genetics 2006, 7:18 http://www.biomedcentral.com/1471-2350/7/18 letion syndromes is the VCFS/DGS, which occurs with an estimated frequency of 1 in every 4000 live births [6] It represents a variety of clinical manifestations including learning disabilities, characteristics facial appearance, velopharyngeal insufficiency, hypernasal speech, cleft palate and conotruncal heart defects [3]. Except for a few rare cases, the remaining patients have smaller deletions nested within the 3 Mb typically deleted region (TDR) [12]

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