410
Applications of Neurogenomics in Neurological Disorders
Many neurological conditions are caused by immensely heterogeneous gene muta-
tions. Role of genetic factors in the etiology of complex diseases remains largely
unresolved. Using genome-wide associations in millions of patient medical records,
a study demonstrated that common variants associated with complex diseases are
enriched in the genes indicated by the “Mendelian code” – a phenotypic code that
links each complex disorder to a unique collection of Mendelian loci (Blair et al.
2013 ). The study identifi ed widespread comorbidity between Mendelian-Mendelian
and Mendelian-complex disease pairs.
Pathomechanism of many neurological and psychiatric disorders is poorly
understood and genomic studies will not only contribute to better understanding but
also improve molecular diagnostics. The current diagnostic process is often long
and complex with most patients undergoing multiple invasive and costly investiga-
tions without ever reaching a conclusive diagnosis. The advent of massively paral-
lel, NGS promises to revolutionize genetic testing and shorten the diagnostic
process for many of these patients.
Genetic disorders can involve multiple systems and with predominant involve-
ment of the nervous system, they are referred to as neurogenetic disorders. Some of
the disorders described in the following sections have a signifi cant neurogenetic com-
ponent. Most of the genetic disorders are caused by point mutations. Deletions are
less frequent and may be overlooked by DNA mapping. It is diffi cult to fi nd the loca-
tion of a gene buried in the tangle of chromosomal DNA in the nucleus. WGS may
facilitate identifi cation of alleles that cause disease. However, even in cases with
simple patterns of inheritance, the relationship between disease phenotypes and their
corresponding genetic changes can be complicated. Comprehensive diagnostic assays
must therefore identify all possible DNA changes in each haplotype and determine
Fig. 12.1 Relationships of neurogenomics with other omics
12 Personalized Management of Neurological Disorders