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

J. L. Cross, J. Iben, Claire Simpson, A. Thurm, S. Swedo, E. Tierney, J. E. Bailey-Wilson, L. G. Biesecker, F. D. Porter, C. A. Wassif

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)570-575
Number of pages6
JournalClinical Genetics
Volume87
Issue number6
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Smith-Lemli-Opitz Syndrome
High-Throughput Nucleotide Sequencing
Exome
Incidence
Single Nucleotide Polymorphism
Databases
Chromosomes, Human, Pair 17
Genetic Counseling
Population Genetics
Mutation Rate
Health Policy
Gene Frequency
Genes
Research Personnel
Newborn Infant
Mutation
Datasets

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets. / Cross, J. L.; Iben, J.; Simpson, Claire; Thurm, A.; Swedo, S.; Tierney, E.; Bailey-Wilson, J. E.; Biesecker, L. G.; Porter, F. D.; Wassif, C. A.

In: Clinical Genetics, Vol. 87, No. 6, 01.01.2015, p. 570-575.

Research output: Contribution to journalArticle

Cross, JL, Iben, J, Simpson, C, Thurm, A, Swedo, S, Tierney, E, Bailey-Wilson, JE, Biesecker, LG, Porter, FD & Wassif, CA 2015, 'Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets', Clinical Genetics, vol. 87, no. 6, pp. 570-575. https://doi.org/10.1111/cge.12425
Cross, J. L. ; Iben, J. ; Simpson, Claire ; Thurm, A. ; Swedo, S. ; Tierney, E. ; Bailey-Wilson, J. E. ; Biesecker, L. G. ; Porter, F. D. ; Wassif, C. A. / Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets. In: Clinical Genetics. 2015 ; Vol. 87, No. 6. pp. 570-575.
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