A person's genome sequence should be interpreted many times throughout his or her lifetime. A single, simple mutation cannot be the sole determinant of a disease. In the years to come, genomic interpretation will be focused on genetic patterns and biological pathways. In other words, single mutations will no longer be the primary driver of disease. Genomic interpretation will require integrative approaches in order to produce actionable conclusions. Here are the steps for genomic interpretation.
In this study, the authors sequenced genomes using the Illumina HiSeq platform. The sequence read data was realigned to the NCBI reference sequence using the Burrows-Wheeler Aligner (BWA) method. They performed variant calls using Genomic Analysis Tool Kit (GATK) version 2.3-9-gdcdccbb. They derived variant annotation using ALAMUT HT version 1.1.2 and Variant Effect Predictor (VEP) version 2.6. Their results are delivered on an encrypted portable hard drive.
Genomic variants are categorized according to their impact on gene function. Single nucleotide variations can have a profound or a minimal impact on the encoded protein. In addition, transcript selection affects gene expression in different tissues, resulting in different biological outcomes. The degree to which an SNV can alter a particular protein's function will determine its clinical significance. The more complex a variant's impact is, the greater the difficulty associated with its interpretation.
A genome-wide association study of a patient's genome will be useful in identifying patients at risk for disease. This information can lead to secondary findings. The data obtained by genomic analysis may be revised and refined over time. A patient's diagnosis can be individualized by collaboration between the cardiovascular genetics provider and the laboratory. When these two groups work together, they can achieve the best outcomes for patients. And if an individual's genetic profile is complex, they should work with the cardiovascular genetics provider to develop the most accurate and effective genomic interpretation.
Genomic interpretation also helps individuals with serious diseases understand the risks and consequences of certain genetic variations. It also helps in the planning of reproductive and family activities, such as conception and pregnancy. This information can be used in long-term predictions. Further, the information will also be useful for those who seek genetic counseling. However, it is not a cure for all disease. And, as a result, a patient's genome is not a guarantee of a disease or trait.
Clinical genomics must take into account the diversity of human populations, especially when comparing individuals from different parts of the world. Some variants may be more common in diseased individuals than in healthy people. Population stratification can lead to false-positive results. Additionally, a reference panel drawn from a single population may have a falsely high frequency of a variant in one population. The results of genomic studies must be based on a surrogate endpoint to ensure that the treatments are effective.
Genomic testing has great potential to transform health care for some patients. The additional diagnoses obtained through genomic testing will alter the trajectory of a patient's disease. In turn, additional diagnoses will lead to more effective treatment, management, and counseling. Although challenges may exist, it will be possible to overcome these through policy and technological advances. However, the process will require considerable training and expertise to be effective. So, it is important that clinicians understand how genomic testing works in order to make informed decisions for patients.
Public databases of genome sequence data will be critical for clinical genomics. These databases contain information on new gene-disease associations and reclassified variants. The MedSeq Project will deposit all its variant classifications into the ClinVar database. This database will help physicians integrate GS into the clinical practice. Further, public databases will improve the diagnostic yield from genome sequencing. There is a growing need for comprehensive and timely genetic testing.
A specialized geneticist should be consulted when genetic tests are complex. An experienced genetic specialist can help interpret the data and explain the potential medical relevance of the findings. The GR is an acronym that communicates complex genomic data to non-genetic specialists. The first page of the GR summarizes all relevant findings. This includes carrier risk for recessive diseases, monogenic disease, pharmacogenomic results, and blood group antigen summary.
As the cost of sequencing decreases and the knowledge of disease genes grows, clinical genomic testing has become a mandatory component of care for nearly every healthcare provider. Until recently, genetic testing was ordered only by the genetics department, but the limited technology available often slowed this process. A sequential targeted approach to genetic testing slowed the process, and patients often had to wait for expensive diagnostic odysseys. With the advent of genomic testing, all healthcare providers should learn how to perform the tests correctly.
