By CESAR PEREZ
Different diseases have different phenotypes, but there are some diseases with remarkable differences inside the same problem. Consequently, there is a difficulty in detection and treatment. Bainbridge and his team presents a study were they show advantages on the using of whole genome sequencing in the search of variants inside people's genome in order to detect high frequency variants for discriminating heterogeneous diseases from another kind of problems or variants that are benign.
Different diseases have different phenotypes, but there are some diseases with remarkable differences inside the same problem. Consequently, there is a difficulty in detection and treatment. Bainbridge and his team presents a study were they show advantages on the using of whole genome sequencing in the search of variants inside people's genome in order to detect high frequency variants for discriminating heterogeneous diseases from another kind of problems or variants that are benign.
For the study described, the scientists focused
on Dopa (3,4-dihydroxyphenylalanine)–responsive dystonia (DRD), a disease with
Mendelian inheritance. DRD is a clinically and genetically heterogeneous
disorder which makes it ideal for searching the coverage of whole genome
sequencing as a clinical tool. However, there is a difficulty on the diagnosis
of DRD which is symptoms variation along the day, it is very common to find
reduced dystonia by awakening and increasing distonia during midday. Traditionally,
differential diagnosis for DRD was applied including early parkinsonism and cerebral palsy. On the
other hand, clinical diagnosis is focused in a neurological scope, inheritance,
age, presence of certain metabolites, and the response to L-dopa treatment.
Scientist realized a whole genome sequence of
twins diagnosed with DRD, its unaffected older brothers, unaffected parents,
and cousins. Then, all the genetic data was analyzed in order to found single
nucleotide polymorphisms (SNPs). In addition, affected twins were treated with
L-dopa and were monitored. Among the results obtained, a set of putative
nucleotides were found which were probably related to DRD. In order to validate
the variant sites, a set of primers was developed, then PCR was realized. Actually,
designed primers were able to detect the mutation in affected twins, and
parents or relatives. Finally, Twins were treated, and after 4 months of
treatment presented improvements in focusing in school and athletic activities.
This work was important due to the power of
whole genome sequencing could help in the diagnosis and treatment of DRD, plus
another highly heterogeneous symptoms diseases. Sequencing methods not only
could be used to diagnosis, but also to found risk on inheritance of different
disorders. In addition, the analysis of
genomes presents more and more advantages like less time consumption, analysis
of the whole picture of a disorder, or the discovery of new sites related to
diseases. Nevertheless, this technique must face challenges yet: information
among the patients, unknowing variants
and functions, undercovering of the relationship between variants alleles and
phenotypes, or the develop of practical medical databases for the variants'
information.
References:
Bainbridge, M. N., Wiszniewski, W., Murdock, D.
R., Friedman, J., Gonzaga-Jauregui, C., Newsham, I., ... & Gibbs, R. A.
(2011). Whole-genome sequencing for optimized patient management. Science
translational medicine, 3(87), 87re3-87re3.
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