Finding the Rare Pathogenic Variants in a Human Genome | Genetics and Genomics | JAMA | The JAMA Network

Genome Sequencing of Healthy Adults:

This week, we highlight a new education article in JAMA on the use of genome sequencing in screening for healthy individuals with genetic mutations associated with preventable chronic diseases such as cancer and heart disease.

For additional information on the use of genetic screening in healthy adults, please read our recent blog post.

Also, check out a slide presentation by Dr James Evans on genetic screening of adults.

Finding the Rare Pathogenic Variants in a Human Genome | Genetics and Genomics | JAMA | The JAMA Network

JAMA Insights 

Genomics and Precision Health

May 9, 2017

Finding the Rare Pathogenic Variants in a Human Genome

James P. Evans, MD, PhD^1,2; Bradford C. Powell, MD, PhD¹; Jonathan S. Berg, MD, PhD¹

Author Affiliations Article Information

JAMA. 2017;317(18):1904-1905. doi:10.1001/jama.2017.0432

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Audio(17:13)

Genomic Sequencing for the Healthy Individual?: Think Smaller

Decreases in the cost of DNA sequencing have enabled substantial progress in fields ranging from archaeology and evolution to basic biomedical science. Concomitantly, there have been calls for routine genome-scale sequencing of healthy individuals in hopes of discovering clinically important information. For example, discovery of a high risk of breast and ovarian cancer due to a BRCA1/2 mutation can enable aggressive surveillance or risk-reducing surgery.

How It Works

Massively parallel sequencing of the total complement of an individual’s DNA (genome sequencing) has proven to be a powerful diagnostic approach for patients with disorders that have a primarily genetic etiology.¹ Genome-scale sequencing can be performed on DNA from white blood cells or buccal cells from saliva (Audio at time 5:43). In sequence analysis, each individual’s genome contains millions of sites where his or her DNA differs from a reference sequence (typically a composite sequence derived by the international Genome Reference Consortium using data from many genomes). Clinical interpretation requires assessing whether any of these variants (eg, a nucleotide change altering an amino acid or a change that results in premature stop of protein translation) are associated with disease. Such determinations rely on control and population data sets, review of the medical literature, and the patient’s phenotype (Figure).