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Population Screening for Hemoglobinopathy Profiling: Is the Development of a Microarray Worthwhile?

Manousos E Kambouris1

  • 1a The Cancer Institute of New Jersey-Robert Wood Johnson Medical School , New Brunswick , NJ , USA.

Hemoglobin
|June 3, 2016
PubMed
Summary

Single nucleotide extension (SNE) microarrays offer a cost-effective and rapid method for population screening of single nucleotide polymorphisms (SNPs) linked to hemoglobinopathies. This approach presents advantages over whole genome sequencing for large-scale genetic analysis.

Keywords:
Hemoglobinopathiesmicroarray developmentmicroarraysmultiplex polymerase chain reaction (PCR)population screeningsingle nucleotide polymorphims (SNPs)

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Area of Science:

  • Genomics and Genetic Analysis
  • Molecular Diagnostics
  • Bioinformatics

Background:

  • Hemoglobinopathies require affordable and efficient population screening methods for single nucleotide polymorphisms (SNPs).
  • Whole genome or exome sequencing is currently expensive and time-consuming for large-scale genetic analysis.

Purpose of the Study:

  • To present the development of a microarray assay using single nucleotide extension (SNE) for cost-effective SNP detection.
  • To detail the challenges and solutions in microarray assay development, including multiplex PCR, labeling, hybridization, and scoring.

Main Methods:

  • Development of a microarray assay involving multiplex polymerase chain reaction (PCR), labeling, hybridization, and scanning/scoring.
  • Optimization of assay parameters, including dye excitation and in silico scoring rules, accounting for dye decay and bleaching.
  • Implementation of a bottom-up approach to systematically address and resolve technical challenges in assay development.

Main Results:

  • The SNE microarray approach demonstrates potential for affordable and expedient whole population scans for hemoglobinopathy-associated SNPs.
  • The study outlines strategies for managing and overcoming common issues encountered during microarray assay development and implementation.

Conclusions:

  • SNE microarrays are a promising, cost-effective alternative to sequencing for large-scale SNP genotyping in population screening.
  • A systematic, bottom-up development strategy is recommended for robust and reliable microarray assay design, especially for high-volume applications.