Allele-level resolution data at primary HLA typing is the ideal for most histocompatibility testing laboratories. Many high-throughput molecular HLA typing approaches are unable to determine the ...phase of observed DNA sequence polymorphisms, leading to ambiguous results. The use of higher resolution methods is often restricted due to cost and time limitations. Here we report on the feasibility of using Pacific Biosciences' Single Molecule Real-Time (SMRT) DNA sequencing technology for high-resolution and high-throughput HLA typing. Seven DNA samples were typed for HLA-A, -B and -C. The results showed that SMRT DNA sequencing technology was able to generate sequences that spanned entire HLA Class I genes that allowed for accurate allele calling. Eight novel genomic HLA class I sequences were identified, four were novel alleles, three were confirmed as genomic sequence extensions and one corrected an existing genomic reference sequence. This method has the potential to revolutionize the field of HLA typing. The clinical impact of achieving this level of resolution HLA typing data is likely to considerable, particularly in applications such as organ and blood stem cell transplantation where matching donors and recipients for their HLA is of utmost importance.
Objectives: To evaluate co‐segregation and genetic associations between von Willebrand's disease (vWD) and psychotic disorders.
Methods: The study was initiated following ascertainment of a nuclear ...family in which four members were diagnosed with vWD and psychotic/mood disorders. As co‐segregation was uncertain in the extended pedigree, we also investigated population‐based linkage and association using polymorphisms of vWF, the gene conferring susceptibility to vWD. Three common vWF polymorphisms were investigated among 194 patients with psychotic disorders (bipolar I disorder, BD I; schizoaffective disorder, SZA and schizophrenia, SZ) and their parents. The cases were also compared with unrelated population‐based controls (n = 183).
Results: The transmission disequilibrium test and related analyses suggested nominally significant transmission distortion of one allele and related haplotypes to the probands from their parents. The most significant results were obtained among patients with BD I, and similar trends were also evident in the SZ sample. Comparisons between the cases and population‐based controls did not reveal associations, though marginally significant case–control differences were obtained in the BD I sample.
Conclusions: These studies are consistent with association and linkage between vWF and BD I. However, given the relatively small sample, stochastic variation is an alternative explanation.
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