A novel, single nucleotide polymorphism-based assay to detect 22q11 deletions

Area of Science:

• Genetics and Molecular Biology
• Clinical Diagnostics
• Human Chromosome Analysis

Background:

• 22q11 deletion syndrome (22q11DS), encompassing velocardiofacial, DiGeorge, and conotruncal anomaly face syndromes, results from microdeletions on chromosome 22q11.
• Traditional diagnostic methods like FISH may not detect all deletion variations or related genetic anomalies.
• A need exists for more precise and sensitive diagnostic tools for 22q11DS.

Purpose of the Study:

• To develop and validate a novel, high-resolution single-nucleotide polymorphism (SNP) genotyping assay for detecting 22q11 deletions.
• To assess the sensitivity and specificity of the SNP assay compared to traditional FISH methods.
• To identify a minimal set of SNPs sufficient for unambiguous diagnosis of 22q11DS.

Main Methods:

• Development of a high-resolution SNP genotyping assay targeting chromosome 22q11.
• Validation of the assay using DNA from 110 non-deleted controls and 77 patients with 22q11DS previously tested by FISH.
• Utilized Bayesian networks to identify a set of 17 informative SNPs for deletion status ascertainment.

Main Results:

• The SNP genotyping assay demonstrated 100% sensitivity in detecting 22q11 deletions.
• The assay successfully identified a case of segmental uniparental disomy at 22q11, which was missed by FISH.
• A set of 17 SNPs was identified as sufficient for unambiguous diagnosis of 22q11DS.

Conclusions:

• The novel SNP-based assay is a highly accurate, sensitive, and specific method for diagnosing 22q11 deletion syndrome.
• This assay offers improved diagnostic capability, including the detection of complex genetic events like segmental uniparental disomy.
• The SNP assay represents a significant advancement in the genetic testing for 22q11DS.