Dataset Information

Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model.

ABSTRACT: BACKGROUND: Monogenic diabetes is a genetic disease often caused by mutations in genes involved in beta-cell function. Correct sub-categorization of the disease is a prerequisite for appropriate treatment and genetic counseling. Target-region capture sequencing is a combination of genomic region enrichment and next generation sequencing which might be used as an efficient way to diagnose various genetic disorders. We aimed to develop a target-region capture sequencing platform to screen 117 selected candidate genes involved in metabolism for mutations and to evaluate its performance using monogenic diabetes as a study-model. RESULTS: The performance of the assay was evaluated in 70 patients carrying known disease causing mutations previously identified in HNF4A, GCK, HNF1A, HNF1B, INS, or KCNJ11. Target regions with a less than 20-fold sequencing depth were either introns or UTRs. When only considering translated regions, the coverage was 100% with a 50-fold minimum depth. Among the 70 analyzed samples, 63 small size single nucleotide polymorphisms and indels as well as 7 large deletions and duplications were identified as being the pathogenic variants. The mutations identified by the present technique were identical with those previously identified through Sanger sequencing and Multiplex Ligation-dependent Probe Amplification. CONCLUSIONS: We hereby demonstrated that the established platform as an accurate and high-throughput gene testing method which might be useful in the clinical diagnosis of monogenic diabetes.

SUBMITTER: Gao R

PROVIDER: S-EPMC3943834 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model.

Gao Rui R Liu Yanxia Y Gjesing Anette Prior AP Hollensted Mette M Wan Xianzi X He Shuwen S Pedersen Oluf O Yi Xin X Wang Jun J Wang Jun J Hansen Torben T

BMC genetics 20140129

<h4>Background</h4>Monogenic diabetes is a genetic disease often caused by mutations in genes involved in beta-cell function. Correct sub-categorization of the disease is a prerequisite for appropriate treatment and genetic counseling. Target-region capture sequencing is a combination of genomic region enrichment and next generation sequencing which might be used as an efficient way to diagnose various genetic disorders. We aimed to develop a target-region capture sequencing platform to screen 1 ...[more]

PMID: 24476040

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Project description:Rubus (Rosaceae) comprises more than 500 species with additional commercially cultivated raspberries and blackberries. The most recent (> 100 years old) global taxonomic treatment of the genus defined 12 subgenera; two subgenera were subsequently described and some species were rearranged. Intra- and interspecific ploidy levels and hybridization make phylogenetic estimation of Rubus challenging. Our objectives were to estimate the phylogeny of 94 taxonomically and geographically diverse species and three cultivars using chloroplast DNA sequences and target capture of approximately 1,000 low copy nuclear genes; estimate divergence times between major Rubus clades; and examine the historical biogeography of species diversification. Target capture sequencing identified eight major groups within Rubus. Subgenus Orobatus and Subg. Anoplobatus were monophyletic, while other recognized subgenera were para- or polyphyletic. Multiple hybridization events likely occurred across the phylogeny at subgeneric levels, e.g., Subg. Rubus (blackberries) × Subg. Idaeobatus (raspberries) and Subg. Idaeobatus × Subg. Cylactis (Arctic berries) hybrids. The raspberry heritage within known cultivated blackberry hybrids was confirmed. The most recent common ancestor of the genus was most likely distributed in North America. Multiple distribution events occurred during the Miocene (about 20 Ma) from North America into Asia and Europe across the Bering land bridge and southward crossing the Panamanian Isthmus. Rubus species diversified greatly in Asia during the Miocene. Rubus taxonomy does not reflect phylogenetic relationships and subgeneric revision is warranted. The most recent common ancestor migrated from North America towards Asia, Europe, and Central and South America early in the Miocene then diversified. Ancestors of the genus Rubus may have migrated to Oceania by long distance bird dispersal. This phylogeny presents a roadmap for further Rubus systematics research. In conclusion, the target capture dataset provides high resolution between species though it also gave evidence of gene tree/species tree and cytonuclear discordance. Discordance may be due to hybridization or incomplete lineage sorting, rather than a lack of phylogenetic signal. This study illustrates the importance of using multiple phylogenetic methods when examining complex groups and the utility of software programs that estimate signal conflict within datasets.

Dataset Information

Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model.

Publications

Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model.

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