Combination of real-time PCR and sequencing to detect multiple clinically relevant genetic variations in the lactase gene

Scand J Clin Lab Invest. 2017 Feb;77(1):60-65. doi: 10.1080/00365513.2016.1261408.

Abstract

Background: Lactase persistence is an autosomal dominant trait commonly distributed in Europe as well as some parts of east Africa and the Arabian Peninsula. Using real-time PCR to detect the -13910C > T variant common in the European population is a reliable analysis although other variants in the probe-binding site may cause errors in analysis. The aim of this study was to determine the prevalence of the variants in a Danish cohort examined for lactose intolerance as well as to improve the real-time PCR analysis for detection of the different variants.

Methods: We genotyped 3395 routine samples using real-time PCR for the -13910C > T-variant. All consecutive samples identified as -13910CC were sequenced using Sanger Sequencing. Using the SDS software we examined various quality value settings to improve on the genetic analysis.

Results: Using real-time PCR resulted in 100% successful genotyping of the -13910C > T variant. By using a quality value of 99% and sequencing the undetermined samples we improved the ability of the assay to identify variants other than -13910C > T. This resulted in a reduction of the diagnostic error rate by a factor of 2.4 while increasing the expenses only 3%.

Conclusions: We conclude that using a quality value of 99% in the SDS software significantly improves the diagnostic efficiency of the real-time PCR assay for detecting variants associated to lactase persistence.

Keywords: DNA sequencing; lactose intolerance; molecular diagnostics; real-time PCR; single nucleotide polymorphism.

MeSH terms

  • Alleles
  • Denmark / epidemiology
  • Gene Expression
  • Gene Frequency
  • Genetic Testing
  • Genotype
  • Humans
  • Lactase / deficiency
  • Lactase / genetics*
  • Lactose Intolerance / diagnosis*
  • Lactose Intolerance / epidemiology
  • Lactose Intolerance / genetics*
  • Lactose Intolerance / physiopathology
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Promoter Regions, Genetic*
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Software

Substances

  • Lactase