The answer to your question revolves around what are the added advantages of “triome” over
Singleton: This term refers herein to when only DNA from the patient is sequenced. While not
perfect, most of the advantages of sequencing can be gained from testing the patient alone, at
least in many patients (see below).
Triome: This term refers to when DNA from the patientand both parentsare sequenced. Triome
sequencing offers certain advantages over singleton sequencing, including:
- The primary advantage of triome is the identification ofde novovariants, which are
“new mutations” that are present in the patient but absent in both parents. Triome
sequencing is frequently often used in patients with neurodevelopmental disorders
(intellectual disability, autism, etc.), epilepsy, “syndromes”, and/or birth defects,
whereasde novo variants are fairly common and oftentimes the main cause of the
- Most metabolic disorders are autosomal recessive, in which both parents are (usually
unaffected) carriers of one disease-causing variant each, and the patient inherited both
of these variants, resulting in disease. When two different variants that might be
disease-related are identified in a patient, recessive disease is likely. To be disease
causing, each variant should be on a different chromosome, inherited one each from
both parents (in which the “phase” is termed as being “in trans”). The alternative is that
both variants are located on the same chromosome, inherited from only one parent (in
which the “phase” is termed as being “in cis”). In the latter case, the variants are likely
not disease causal, but could be a risk factor. The easiest, and often the only, way to
determine the phase of the variants (in cis versusin trans) is to sequence at least one
- In the case that one parent is clinically affected, sequencing can determine which of
several “variants of uncertain significance” were inherited from the affected parent.
Obviously, these variants would be more important to consider than are the variants
inherited from the unaffected parent.
The purpose of triome sequencing is to better understand the sequence results in the patient.
Triome sequencing is NOT intended to identify genetic disease or risks is the parents, most of
which will not be identified. Of course, triome sequencing will identify a parent as having a
disease-causing variant if both the patient and a parent share the variant.
Of note, triome sequencing can be used for large panels, whole exome sequencing (WES),
and whole genome sequencing (WGS).
As a practical matter, triome sequencing is recommended forpatients with neurodevelopmental
disorders (intellectual disability, autism, etc.), epilepsy, “syndromes”, and/or birth defects,
whereas in many other settings, singleton sequencing is appropriate.