Browsing by Subject "Next-generation sequencing"

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    Identification of ATP8A2 gene mutation in a consaguineous family segregating cerebellar atrophy and quadrupedal gait
    (2012) Onat, Onur Emre
    Cerebellar ataxia, mental retardation, and dysequilibrium syndrome is a rare and heterogeneous neurodevelopmental disorder characterized by cerebellar atrophy, dysarthric speech, and quadrupedal locomotion. Here, a consanguineous family with four affected individuals which suggest an autosomal recessive inheritance was investigated. Homozygosity mapping analysis using high-resolution genotyping arrays in two affected individuals revealed four shared homozygous regions on 13q12, 19p13.3, 19q13.2, and 20q12. Target enrichment and next-generation sequencing of these regions in an affected individual was uncovered 11 novel protein altering variants which were filtered against dbSNP132 and 1000 genomes databases. Further population filtering using personal genome databases and previous exome sequencing datasets, segregation analysis, geographically-matched population screening, and prediction approaches revealed a novel missense mutation, p.I376M, in ATP8A2 segregated with the phenotype in the family. The mutation resides in a highly conserved C-terminal transmembrane region of E1-E2 ATPase domain. ATP8A2 is mainly expressed in brain, in particular with the highest levels at cerebellum which is a crucial organ for motor coordination. Mice deficient with Atp8a2 revealed impaired axonal transport in the motor neurons associated with severe cerebellar ataxia and body tremors. Recently, an unrelated individual with a de novo t(10;13) balanced translocation whose one of the ATP8A2 allele was disrupted has been identified. This patient shares similar neurological phenotypes including severe mental retardation and hypotonia. These findings suggest a role for ATP8A2 in the neurodevelopment, especially in the development of cerebro-cerebellar structures required for posture and gait in humans.
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    Improving genome assemblies using multi-platform sequence data
    (Springer, 2015-09) Kavak, P.; Ergüner, B.; Üstek, D.; Yüksel, B.; Saǧıroǧlu, M. Ş.; Güngör, T.; Alkan, Can
    Accurate de novo assembly using short reads generated by next generation sequencing technologies is still an open problem. Although there are several assembly algorithms developed for data generated with different sequencing technologies, and some that can make use of hybrid data, the assemblies are still far from being perfect. There is still a need for computational approaches to improve draft assemblies. Here we propose a new method to correct assembly mistakes when there are multiple types of data generated using different sequencing technologies that have different strengths and biases. We exploit the assembly of highly accurate short reads to correct the contigs obtained from less accurate long reads. We apply our method to Illumina, 454, and Ion Torrent data, and also compare our results with existing hybrid assemblers, Celera and Masurca. © Springer International Publishing Switzerland 2016.