Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 49 |
| Journal | Genome Medicine |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - May 30 2017 |
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ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Genetics(clinical)
Cite this
Genome annotation for clinical genomic diagnostics : Strengths and weaknesses. / Steward, Charles A.; Parker, Alasdair P.J.; Minassian, Berge A.; Sisodiya, Sanjay M.; Frankish, Adam; Harrow, Jennifer.
In: Genome Medicine, Vol. 9, No. 1, 49, 30.05.2017.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Genome annotation for clinical genomic diagnostics
T2 - Strengths and weaknesses
AU - Steward, Charles A.
AU - Parker, Alasdair P.J.
AU - Minassian, Berge A.
AU - Sisodiya, Sanjay M.
AU - Frankish, Adam
AU - Harrow, Jennifer
PY - 2017/5/30
Y1 - 2017/5/30
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85019973466&partnerID=8YFLogxK
U2 - 10.1186/s13073-017-0441-1
DO - 10.1186/s13073-017-0441-1
M3 - Review article
C2 - 28558813
AN - SCOPUS:85019973466
VL - 9
JO - Genome Medicine
JF - Genome Medicine
SN - 1756-994X
IS - 1
M1 - 49
ER -