Neurological disorders, genetic correlations, and the role of exome sequencing

Abstract

Genomic information access and utilization by researchers and clinicians have barely begun the journey for fulfillment of their full potential in the research and clinical arenas. Exciting is the potential depth and breadth of research, clinical applications, and more personalized medicine, that remain on the horizon. Exome sequencing has clarified the responsibilities of over 130 genes, greatly expanding the medical genetics database and enabling the development of orphan diseasebased pharmaceuticals. The focus of our research efforts was to review several literature sources related to rare genomic disease research and exome sequencing, as well as to review the new research and diagnostic strategies that were utilized. Using a systems approach, under discussion are neurology, neuropathy, and the central nervous and musculoskeletal systems. Also discussed will be the topics of inborn errors of metabolism, and the genetic targets related to developmental delay. Recommendations for future research will also be discussed. Exome sequencing A review of new strategies for rare genomic disease researchThis literature review will examine several publications in which the authors demonstrate the success of whole exome sequencing (WES) in circumstances where traditional methods have presented ambiguous interpretations or failed altogether, for instance, single -subject populations, large candidate counts and reduced reproductive fitness [1]. By supporting exome sequencing, we will show that there is an increasing need for polymorphism databases and assay strategies that do not depend on positional information, if genomic medicine is to advance its research and clinical utility. Within our review, we will discuss the research related to neurology, neuropathy, the central nervous system, the musculoskeletal system, inborn errors of metabolism, and the genetic targets related to developmental delay. Recommendations for future research will also be discussed. Disease survey NeurologyPositional cloning techniques have thus far unveiled 19 contributory genes in the study of 31 genetic variations of autosomal dominant spinocerebellar ataxia [2]. The method has yet to overcome the challenges that presented, such as phenotypic and biological manifestations which do not correlate well to molecular mutations due to the exceedingly complex nature of the brain. Exome sequencing has, however, shed additional light on causal mutations for sensory motor neuropathy with ataxia [3], which presents with cerebellar dysfunction, Spinocerebellar Ataxia with Psychomotor Retardation [4], and Spastic Ataxia-Neuropathy syndrome that manifested with remarkable variety between two brothers [5] due to different mutations in the same protease subunits.A United States incidence of 1 in 12,500 live births makes neuronal ceroid lipofuscinoses the most common group of inherited neurological degenerative disorders [6]. Whether examining the mitochondrial defect implicated in prenatal ventriculomegaly [7], the often early-stage atypical presentation...

The genetic epidemiology of the form of microcephaly ascribed to mutation at the WDR62 locus

“…Brown and Meloche suggest that exome sequencing will be useful for diagnosing brain formation disorders such as polymicrogyria, citing Murdock et al (11,20).…”

“…As we have seen, the frequency of the mutant depends in part on F. As noted above, the value of f Y in Eq. [20], which will be a small positive quantity in most populations, increases C AB and may be neglected.…”