Next Generation Sequencing and Bioinformatics Analysis of Family Genetic Inheritance

Abstract

Mendelian and complex genetic trait diseases continue to burden and affect society both socially and economically. The lack of effective tests has hampered diagnosis thus, the affected lack proper prognosis. Mendelian diseases are caused by genetic mutations in a singular gene while complex trait diseases are caused by the accumulation of mutations in either linked or unlinked genomic regions. Significant advances have been made in identifying novel diseases associated mutations especially with the introduction of next generation and third generation sequencing. Regardless, some diseases are still without diagnosis as most tests rely on SNP genotyping panels developed from population based genetic analyses. Analysis of family genetic inheritance using whole genomes, whole exomes or a panel of genes has been shown to be effective in identifying disease-causing mutations. In this review, we discuss next generation and third generation sequencing platforms, bioinformatic tools and genetic resources commonly used to analyze family based genomic data with a focus on identifying inherited or novel disease-causing mutations. Additionally, we also highlight the analytical, ethical and regulatory challenges associated with analyzing personal genomes which constitute the data used for family genetic inheritance.

Genetics Matters: Voyaging from the Past into the Future of Humanity and Sustainability

“…The human genome was completed in the early 2000s, around the same time as a handful of model organisms, including arabidopsis ( Arabidopsis thaliana ), rice ( Oryza sativa ), and fruit fly ( Drosophila melanogaster ) ( Figure 1 ). After the birth of next-generation sequencing (NGS) technologies in the mid-2000s, hundreds of other organisms had their genomes completely sequenced, and millions of genes have been annotated, be they genes responsible for severe diseases in humans or genes conferring resistance and tolerance in crops [ 29 ]. This is especially true for microorganisms with small genome sequences, such as viruses and single-celled organisms (bacteria and protozoa), where the number of genomes being sequenced for these organisms has been exploding [ 30 ].…”

Focused Strategies for Defining the Genetic Architecture of Congenital Heart Defects

“…Another option to capture genetic variation is next generation sequencing (NGS). Briefly, NGS reads millions of small fragments of DNA in parallel [51]; these reads must be pieced back together using bioinformatics tools, which include quality control, alignment to a reference genome, and variant calling [52,53]. NGS can be used to capture SNV and some indels as well as CNV.…”

Application of next generation sequencing in the screening of monogenic diseases in China, 2021: a consensus among Chinese newborn screening experts

“…In recent years, the advent of next generation sequencing (NGS) has led to significant breakthroughs in the diagnosis of genetic diseases. Improvement in analytical accuracy, reporting turn-around-time and standardization of result interpretation as well declining sequencing costs have led to rapidly increased adoption of NGS-based genetic testing in regular clinical practice by domestic and overseas experts [11][12][13][14][15][16][17][18][19][20][21][22][23]. In addition, the widespread application of various molecular diagnostic technologies, especially NGS, in the diagnosis of genetic diseases has helped discover a large number of disease-causing variants.…”