Global Analysis of Disease-related DNA Sequence Variation in 10 Healthy Individuals: Implications for Whole Genome-based Clinical Diagnostics

Overview

Journal Genet Med

Publisher Elsevier

Specialty Genetics

Date 2011 Feb 18

PMID 21325948

Citations 19

Authors

Barry Moore

Hao Hu

Marc Singleton

Francisco M De La Vega

Martin G Reese

Mark Yandell

Affiliations

Soon will be listed here.

Abstract

Background: Understanding how sequence variants within healthy genomes are distributed with respect to ethnicity and disease-implicated genes is an essential first step toward establishing baselines for personalized genomic medicine.

Methods: In this study, we present an analysis of 10 genomes from healthy individuals of various ethnicities, produced using six different sequencing technologies. In total, these genomes contain more than 34 million single-nucleotide variants.

Results: We have analyzed these variants from a clinical perspective, assaying the influence of sequencing technology and ethnicity on prognosis. We have also examined the utility of OMIM and the disease-gene literature for determining the impact of rare, personal variants on an individual's health.

Conclusions: Our analyses demonstrate that clinical prognoses are complicated by sequencing platform-specific errors and ethnicity. We show that disease-causing alleles are globally distributed along ethnic lines, with alleles known to be disease causing in Eurasians being significantly more likely to be homozygous in Africans.

Citing Articles

Evaluating the Calling Performance of a Rare Disease NGS Panel for Single Nucleotide and Copy Number Variants.

Cacheiro P, Ordonez-Ugalde A, Quintans B, Pineiro-Hermida S, Amigo J, Garcia-Murias M Mol Diagn Ther. 2017; 21(3):303-313.

PMID: 28290094 DOI: 10.1007/s40291-017-0268-x.

Psychological and behavioural impact of returning personal results from whole-genome sequencing: the HealthSeq project.

Sanderson S, Linderman M, Suckiel S, Zinberg R, Wasserstein M, Kasarskis A Eur J Hum Genet. 2017; 25(3):280-292.

PMID: 28051073 PMC: 5315514. DOI: 10.1038/ejhg.2016.178.

Kuwaiti population subgroup of nomadic Bedouin ancestry-Whole genome sequence and analysis.

John S, Thareja G, Hebbar P, Behbehani K, Thanaraj T, Alsmadi O Genom Data. 2015; 3:116-27.

PMID: 26484159 PMC: 4535864. DOI: 10.1016/j.gdata.2014.11.016.

Sequence and analysis of a whole genome from Kuwaiti population subgroup of Persian ancestry.

Thareja G, John S, Hebbar P, Behbehani K, Thanaraj T, Alsmadi O BMC Genomics. 2015; 16:92.

PMID: 25765185 PMC: 4336699. DOI: 10.1186/s12864-015-1233-x.

Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins.

Carmi S, Hui K, Kochav E, Liu X, Xue J, Grady F Nat Commun. 2014; 5:4835.

PMID: 25203624 PMC: 4164776. DOI: 10.1038/ncomms5835.

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