Homozygosity Mapping using Whole-Exome Sequencing: A Valuable Approach for Pathogenic Variant Identification in Genetic Diseases

Jorge Oliveira, Rute Pereira, Rosário Santos, Mário Sousa

Abstract

In the human genome, there are homozygous regions presenting as sizeable stretches, or ‘runs’ of homozygosity (ROH). The length of these ROH is dependent on the degree of shared parental ancestry, being longer in individuals descending from consanguineous marriages or those from isolated populations. Homozygosity mapping is a powerful tool in clinical genetics. It relies on the assumption that, due to identity-by-descent, individuals affected by a recessive disease are likely to have homozygous markers surrounding the disease locus. Consequently, the analysis of ROH shared by affected individuals in the same kindred often helps to identify the disease-causing gene. However, scanning the entire genome for blocks of homozygosity, especially in sporadic cases, is not a straight-forward task. Whole-exome sequencing (WES) has been shown to be an effective approach for finding pathogenic variants, particularly in highly heterogeneous genetic diseases. Nevertheless, the huge amount of data, especially variants of unknown clinical significance, and the presence of false-positives due to sequencing artifacts, makes WES analysis complex. This paper briefly reviews the different algorithms and bioinformatics tools available for ROH identification. We emphasize the importance of performing ROH analysis using WES data as an effective way to improve diagnostic yield.

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Paper Citation


in Harvard Style

Oliveira J., Pereira R., Santos R. and Sousa M. (2017). Homozygosity Mapping using Whole-Exome Sequencing: A Valuable Approach for Pathogenic Variant Identification in Genetic Diseases . In Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2017) ISBN 978-989-758-214-1, pages 210-216. DOI: 10.5220/0006248502100216


in Bibtex Style

@conference{bioinformatics17,
author={Jorge Oliveira and Rute Pereira and Rosário Santos and Mário Sousa},
title={Homozygosity Mapping using Whole-Exome Sequencing: A Valuable Approach for Pathogenic Variant Identification in Genetic Diseases},
booktitle={Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2017)},
year={2017},
pages={210-216},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0006248502100216},
isbn={978-989-758-214-1},
}


in EndNote Style

TY - CONF
JO - Proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2017)
TI - Homozygosity Mapping using Whole-Exome Sequencing: A Valuable Approach for Pathogenic Variant Identification in Genetic Diseases
SN - 978-989-758-214-1
AU - Oliveira J.
AU - Pereira R.
AU - Santos R.
AU - Sousa M.
PY - 2017
SP - 210
EP - 216
DO - 10.5220/0006248502100216