AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data

Mathieu Quinodoz; Virginie G Peter; Nicola Bedoni; Béryl Royer Bertrand; Katarina Cisarova; Arash Salmaninejad; Neda Sepahi; Raquel Rodrigues; Mehran Piran; Majid Mojarrad; Alireza Pasdar; Ali Ghanbari Asad; Ana Berta Sousa; Luisa Coutinho Santos; Andrea Superti-Furga; Carlo Rivolta

doi:10.1038/s41467-020-20584-4

AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data

Nat Commun. 2021 Jan 22;12(1):518. doi: 10.1038/s41467-020-20584-4.

Authors

Mathieu Quinodoz^{1

2

3}, Virginie G Peter^{1

2

3

4}, Nicola Bedoni⁵, Béryl Royer Bertrand⁵, Katarina Cisarova⁵, Arash Salmaninejad⁶, Neda Sepahi⁷, Raquel Rodrigues⁸, Mehran Piran^{7

9}, Majid Mojarrad⁶, Alireza Pasdar^{6

10}, Ali Ghanbari Asad⁷, Ana Berta Sousa^{8

11}, Luisa Coutinho Santos¹², Andrea Superti-Furga⁵, Carlo Rivolta^{13

14

15}

Affiliations

¹ Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
² Department of Ophthalmology, University of Basel, Basel, Switzerland.
³ Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
⁴ Institute of Experimental Pathology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁵ Service of Medical Genetics, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁶ Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁷ Noncommunicable Diseases Research Center, Fasa University of Sciences, Fasa, Iran.
⁸ Department of Medical Genetics, Hospital Santa Maria, Centro Hospitalar Universitário Lisboa Norte (CHULN), Lisbon Academic Medical Center (CAML), Lisbon, Portugal.
⁹ Bioinformatics and Computational Biology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
¹⁰ Division of Applied Medicine, Medical School, University of Aberdeen, Aberdeen, UK.
¹¹ Medical Faculty, Lisbon University, Lisbon, Portugal.
¹² Instituto de Oftalmologia Dr Gama Pinto, Lisbon, Portugal.
¹³ Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland. [email protected].
¹⁴ Department of Ophthalmology, University of Basel, Basel, Switzerland. [email protected].
¹⁵ Department of Genetics and Genome Biology, University of Leicester, Leicester, UK. [email protected].

Abstract

Homozygosity mapping is a powerful method for identifying mutations in patients with recessive conditions, especially in consanguineous families or isolated populations. Historically, it has been used in conjunction with genotypes from highly polymorphic markers, such as DNA microsatellites or common SNPs. Traditional software performs rather poorly with data from Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS), which are now extensively used in medical genetics. We develop AutoMap, a tool that is both web-based or downloadable, to allow performing homozygosity mapping directly on VCF (Variant Call Format) calls from WES or WGS projects. Following a training step on WES data from 26 consanguineous families and a validation procedure on a matched cohort, our method shows higher overall performances when compared with eight existing tools. Most importantly, when tested on real cases with negative molecular diagnosis from an internal set, AutoMap detects three gene-disease and multiple variant-disease associations that were previously unrecognized, projecting clear benefits for both molecular diagnosis and research activities in medical genetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromosome Mapping / methods*
Computational Biology / methods*
Exome Sequencing / methods
Genetic Predisposition to Disease / genetics
Genome, Human / genetics*
Genotype
High-Throughput Nucleotide Sequencing / methods*
Homozygote
Humans
Internet
Mutation
Polymorphism, Single Nucleotide*
Reproducibility of Results
Software*