Page 29 - Genomic Medicine in Emerging Economies

18 CHAPTER 2: Taking Genomics From the Bench to the Bedside in Developing Countries

of financing these tests out of their own pockets. These continue to be chal-
lenges because the cost of service contracts, reagents, other consumables, etc.,
are constantly escalating, and a service dependent on payment by the customer
where the markup is kept deliberately small to make them affordable to those
who need it cannot survive without cash infusion from philanthropic donors.
Issues related to financing tests, perception about the usefulness of these tests
among policymakers and administrators, and the high cost of the maintenance
contract once the warranty period passed were additional challenges that we
had to face (Sirisena et al., 2016). On the other hand, the challenge for bio-
informatics and reporting include the interpretation of variants in the context
of the phenotypic data, dealing with variants of uncertain clinical significance
(VUS), nonrepresentation of variants found in the Sri Lankan population in
public databases, and dealing with incidental findings. We expect that some of
these challenges will be resolved as we sequence more and more exomes and
understand the allele frequencies of variants in our own population. We believe
that the rapid accumulation of data and the availability of updated popula-
tion frequency databases will also result in improved variant classification and
an overall reduction in inconclusive results (Castéra et al., 2014; Eggington
et al., 2014; Hiraki et al., 2014). The fact, that we were doing our own bioinfor-
matics analysis in-house using already well-established open-source tools and
custom-written program scripts, rather than outsourcing that work as is usu-
ally the case in resource-poor settings, enabled us to have first-hand experience
of handling data generated through NGS and to appreciate the quality issues
related to such data, such as differences in coverage and depth in different parts
of the genome. It also enabled us to have an understanding of the limitations
of the commercial kits that we used and to have meaningful discussions with
the manufacturers on possible requirements for customization of the gene pan-
els for local needs. The ethical, legal, and social implications of moving from
genetic to genomic counseling, managing patient privacy in an atmosphere
of collaborative, open-access public data sharing, and working with families
encountering legal prohibition of selective termination of pregnancies based
on genetic information are some of the other challenging concerns related to
genomic medicine that we have had to tackle (Sirisena et al., 2016).
The implementation of genomic medicine into our routine clinical practice has
facilitated improved care for our patients (all of whom hitherto lacked a pre-
cise genetic diagnosis and appropriate treatment) by enabling us to diagnose
and successfully manage patients with rare disorders, complex disorders with
unusual coexisting phenotypes, and inherited cancer syndromes. It has also
enabled us to build a catalog of genetic variants in the Sri Lankan population.

Experiences similar to that of our own in other developing countries, how-
ever, is often isolated, and there is therefore the need for more widespread
equitable implementation of genomic medicine throughout the developing