Clustering and alignment of polymorphic sequences for HLA-DRB1 genotyping.
Clustering and alignment of polymorphic sequences for HLA-DRB1 genotyping.
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DOI：
10.1371/journal.pone.0059835
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Trucco M
中科院分区：
文献类型：
--
作者：
Ringquist S;Bellone G;Lu Y;Roeder K;Trucco M
人类白细胞抗原基因位于染色体6p 21，具有高度多态性。HLA等位基因与多种表型相关，如发作性睡病、自身免疫以及对感染性疾病的免疫应答。此外，这些基因座的高分辨率基因分型对于实现同种异体移植的长期存活至关重要。开发获得HLA基因型的高分辨率分析的方法将导致更好地理解选择等位基因如何有助于人类健康和疾病风险。从作为溃疡性结肠炎研究的一部分招募的n=383名受试者的队列中获得基因组DNA，并分析HLA-DRB 1。 使用序列特异性寡核苷酸探针和使用Roche/454 GSFLX仪器的下一代测序来确定HLA基因型。开发多态性序列的聚类和比对（CAPSeq）软件应用以分析下一代测序数据。该应用程序从下一代测序数据中生成HLA序列特异性6位基因型信息，使用MUMmer比对序列，并使用R软件包diffusionMap将序列分类到其各自的等位基因组中。结合Bootstrap Aggregating、Bagging以帮助将序列分选到等位基因类别中导致基因分型准确性提高。使用等于60的Bagging迭代，当与序列特异性寡核苷酸探针表征的4位基因型相比时，使用CAPSeq获得的基因分型结果表现出高一致率，在766个（99.1%）等位基因中的759个处匹配。
Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles.
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影响因子：
--
作者：
Bentley G;Higuchi R;Hoglund B;Goodridge D;Sayer D;Trachtenberg EA;Erlich HA
通讯作者：
Erlich HA
影响因子：
--
作者：
Lancaster, A. K.;Single, R. M.;Thomson, G.
通讯作者：
Thomson, G.
影响因子：
46.9
作者：
Rothberg, Jonathan M.;Leamon, John H.
通讯作者：
Leamon, John H.
DOI：
10.1016/j.cccn.2005.06.023
发表时间：
2006-01
期刊：
Clinica chimica acta; international journal of clinical chemistry
影响因子：
--
作者：
Dunbar SA
通讯作者：
Dunbar SA
I级基因座HLA键入的下一代测序。
影响因子：
4.4
作者：
Erlich RL;Jia X;Anderson S;Banks E;Gao X;Carrington M;Gupta N;DePristo MA;Henn MR;Lennon NJ;de Bakker PI
通讯作者：
de Bakker PI