Identification of Genetic Variants and de novo
Mutations Based on NGS
10
Patricia Basurto-Lozada, Carolina Castañeda-Garcia, Raúl Ossio,
and Carla Daniela Robles-Espinoza
Contents
10.1 Introduction: Quick Recap of a Sequencing Experiment Design . . . . . . . . . . . . . . . . . . . . . . . . . 124
10.2 How Are Novel Genetic Variants Identified? . .. .. . .. .. . .. . .. .. . .. .. . .. .. . .. . .. .. . .. .. . .. .. 124
10.2.1 Naive Variant Calling . . . ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... 125
10.2.2 Bayesian Variant Calling . . . . . . . . . . . . . . .. . .. . .. . .. . .. . . .. . .. . .. . .. . . .. . .. . .. . .. . . .. 126
10.2.3 Heuristic Variant Calling . . . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. 128
10.2.4 Other Factors to Take into Account When Performing Variant Calling . . . . . . . . 129
10.2.5 How to Choose an Appropriate Algorithm for Variant Calling? . . . . . . . . . . . . . . . . 130
10.3 Working with Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
10.4 Applying Post-variant Calling Filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
10.5 De novo Genetic Variants: Population-Level Studies and Analyses Using Pedigree
Information . . . . . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. 133
10.6 Filtering Genetic Variants to Identify Those Associated to Phenotypes . . . .. . . .. . . . .. . . .. 134
10.6.1 Variant Annotation . . ..... .... ..... .... ..... .... ..... .... ..... ..... .... ..... .... .... 135
10.6.2 Evaluating the Evidence Linking Variants Causally to Phenotypes . . . . . . . . . . . . . 135
P. Basurto-Lozada · C. Castañeda-Garcia · R. Ossio
Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional
Autónoma de México, Campus Juriquilla, Santiago de Querétaro, México
C. D. Robles-Espinoza (*)
Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional
Autónoma de México, Campus Juriquilla, Santiago de Querétaro, México
Experimental Cancer Genetics, Wellcome Sanger Institute, Cambridge, UK
e-mail: drobles@liigh.unam.mx
# Springer Nature Switzerland AG 2021
M. Kappelmann-Fenzl (ed.), Next Generation Sequencing and Data Analysis, Learning
Materials in Biosciences, https://doi.org/10.1007/978-3-030-62490-3_10
123
Mutations Based on NGS
10
Patricia Basurto-Lozada, Carolina Castañeda-Garcia, Raúl Ossio,
and Carla Daniela Robles-Espinoza
Contents
10.1 Introduction: Quick Recap of a Sequencing Experiment Design . . . . . . . . . . . . . . . . . . . . . . . . . 124
10.2 How Are Novel Genetic Variants Identified? . .. .. . .. .. . .. . .. .. . .. .. . .. .. . .. . .. .. . .. .. . .. .. 124
10.2.1 Naive Variant Calling . . . ..... ..... ..... ..... ..... ..... ..... .... ..... ..... ..... ..... 125
10.2.2 Bayesian Variant Calling . . . . . . . . . . . . . . .. . .. . .. . .. . .. . . .. . .. . .. . .. . . .. . .. . .. . .. . . .. 126
10.2.3 Heuristic Variant Calling . . . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. . . .. 128
10.2.4 Other Factors to Take into Account When Performing Variant Calling . . . . . . . . 129
10.2.5 How to Choose an Appropriate Algorithm for Variant Calling? . . . . . . . . . . . . . . . . 130
10.3 Working with Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
10.4 Applying Post-variant Calling Filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
10.5 De novo Genetic Variants: Population-Level Studies and Analyses Using Pedigree
Information . . . . . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. . . .. . .. . . .. . .. . . .. . .. . . .. . .. . . .. 133
10.6 Filtering Genetic Variants to Identify Those Associated to Phenotypes . . . .. . . .. . . . .. . . .. 134
10.6.1 Variant Annotation . . ..... .... ..... .... ..... .... ..... .... ..... ..... .... ..... .... .... 135
10.6.2 Evaluating the Evidence Linking Variants Causally to Phenotypes . . . . . . . . . . . . . 135
P. Basurto-Lozada · C. Castañeda-Garcia · R. Ossio
Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional
Autónoma de México, Campus Juriquilla, Santiago de Querétaro, México
C. D. Robles-Espinoza (*)
Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional
Autónoma de México, Campus Juriquilla, Santiago de Querétaro, México
Experimental Cancer Genetics, Wellcome Sanger Institute, Cambridge, UK
e-mail: drobles@liigh.unam.mx
# Springer Nature Switzerland AG 2021
M. Kappelmann-Fenzl (ed.), Next Generation Sequencing and Data Analysis, Learning
Materials in Biosciences, https://doi.org/10.1007/978-3-030-62490-3_10
123