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Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets.

Abstract
Data from massively parallel sequencing or 'Next Generation Sequencing' of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single nucleotide polymorphism (SNP) or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes, we analyzed the causative gene for the disorder Smith-Lemli-Opitz Syndrome (SLOS), the 7-dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening.
AuthorsJ L Cross, J Iben, C L Simpson, A Thurm, S Swedo, E Tierney, J E Bailey-Wilson, L G Biesecker, F D Porter, C A Wassif
JournalClinical genetics (Clin Genet) Vol. 87 Issue 6 Pg. 570-5 (Jun 2015) ISSN: 1399-0004 [Electronic] Denmark
PMID24813812 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
CopyrightPublished 2014. This article is a U.S. Government work and is in the public domain in the USA.
Chemical References
  • Oxidoreductases Acting on CH-CH Group Donors
  • 7-dehydrocholesterol reductase
Topics
  • Alleles
  • Datasets as Topic
  • Gene Frequency
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Incidence
  • Mutation
  • Oxidoreductases Acting on CH-CH Group Donors (genetics)
  • Smith-Lemli-Opitz Syndrome (epidemiology, genetics)

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