Authors:
Jorge Oliveira
1
;
2
;
Rute Pereira
1
;
Rosário Santos
2
and
Mário Sousa
1
Affiliations:
1
Universidade do Porto, Portugal
;
2
Centro Hospitalar do Porto, Portugal
Keyword(s):
Whole-Exome Sequencing, Homozygosity Mapping, Next-Generation Sequencing, Clinical Genetics.
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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