Kasturi Haldar | Search bioRxiv

bioRxiv2016

Next generation whole genome sequencing of Plasmodium falciparum using NextSeq500 technology in India

Plasmodium falciparum is a protozoan parasite that causes the deadliest form of human malaria. Although, malaria burdens worldwide have decreased substantially over the last decade (WHO, 2014), genetic variation and adaptation by parasite strains against drugs and vaccines present significant challenges for the elimination of malaria (Ariey et al., 2014; Neafsey et al., 2015). India has formally launched a malaria elimination campaign (NVBDCP, 2016). Therefore, early in-country detection of drug resistance and/or immune evasion will be important for the program. Presently, the majority of surveillance methods in India detect a limited number of known polymorphisms (Campino et al., 2011; Chatterjee et al., 2016; Daniels et al., 2008; Mishra et al., 2015; Neafsey et al., 2012; Neafsey et al., 2008). A recently reported amplicon sequencing method enables targeted re-sequencing of a panel of genes (Rao et al., 2016). However, the capacity to identify new genes of resistance/immune evasion by whole genome sequencing (WGS) through next generation sequencing (NGS) in India, has remained elusive. Here we report the first WGS of P. falciparum strain performed by Eurofins Genomics India Pvt. Ltd at its Bengaluru division within 40 days of sample submission. Our data establish that timely, commercial WGS through NGS in India can be applied to P. falciparum to greatly empower the malaria elimination agenda in India.

Genomics↗

bioRxiv2016

Case Report: Aggressive Tibial Pseudarthrosis as Primary Symptom in Infant with Neurofibromatosis

Neurofibromatosis (NF1) is a rare genetic neurologic disorder with over 30 distinct clinical manifestations, the top 3 of which include cafe-au-lait spotting, benign tumors and abnormal freckling. Pseudarthrosis (PA), also known as a \"false joint,\" is a rare subset of NF1 symptomology, characterized by bone fractures and nonunion caused by severe bowing of long bones. To date, it is invariably reported as secondary to NF1, commonly at 24 months of age. Here we describe a 4-month old infant who presented with PA as primary symptom, and in absence of an NF1 first-degree relative. Initial manifestation was guarding of the leg and increased irritability upon palpation of the knee, subsequent to light playful jostling. Physician examination revealed gross anterolateral bowing of the left leg. Radiography confirmed tibia-fibula bowing and pathologic transverse fracture at tibia diaphysis, characteristic of PA. Cafe-au-lait spots developed at 6 months subsequent to PA, but with number and size well below the National Institutes of Health criteria for NF1 diagnosis. At 14 months, exome sequencing established definitive NF1 diagnosis. Treatment involved PA takedown surgery. Although healing was seen after 2 months, complications emerged by 6 months. This case suggests that for primary PA without clear etiology, first-contact and consulting physicians should pay careful attention and be vigilant to timing of clinical onset and severity. Early, severe primary PA warrants accelerated NF1 exome sequencing, suggesting expansion of existing federal guidelines may be necessary to improve detection and prognosis of this rare, debilitating but readily managed condition.\n\nFinancial DisclosureThe authors have no financial relationships relevant to this article to disclose\n\nConflict of InterestThe authors have no conflicts of interest to disclose\n\nClinical Trial RegistrationNA

Genetics↗