2017/05/30 by Charles A. Steward, Alasdair Parker, Berge A. Minassian +3 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Genomics and Rare Diseases #Genomic variations and chromosomal abnormalities #Genomics and Phylogenetic Studies #Annotation #Genome #Computational biology #Genome project #Exome #Pseudogene #Exome sequencing #Identification (biology) #Human genome #DNA sequencing #Genomics #Gene Annotation #Human genetics #Genetics #Biology #Gene #Mutation
paper · pdf · doi:10.1186/s13073-017-0441-1
openalex publication_date 2017/05/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The Human Genome Project and advances in DNA sequencing technologies have revolutionized the identification of genetic disorders through the use of clinical exome sequencing. However, in a considerable number of patients, the genetic basis remains unclear. As clinicians begin to consider whole-genome sequencing, an understanding of the processes and tools involved and the factors to consider in the annotation of the structure and function of genomic elements that might influence variant identification is crucial. Here, we discuss and illustrate the strengths and weaknesses of approaches for the annotation and classification of important elements of protein-coding genes, other genomic elements such as pseudogenes and the non-coding genome, comparative-genomic approaches for inferring gene function, and new technologies for aiding genome annotation, as a practical guide for clinicians when considering pathogenic sequence variation. Complete and accurate annotation of structure and function of genome features has the potential to reduce both false-negative (from missing annotation) and false-positive (from incorrect annotation) errors in causal variant identification in exome and genome sequences. Re-analysis of unsolved cases will be necessary as newer technology improves genome annotation, potentially improving the rate of diagnosis.