Collection articles
The Collection contains relevant articles from Nature Publishing Group. These articles are available free to registered users until 30 April 2008.
Feature
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Replicating genotype–phenotype associations
Journal:Nature 447, 655-660 (7 June 2007); doi:10.1038/447655a
What constitutes replication of a genotype–phenotype association, and how best can it be achieved?
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Review
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Microarray technology: beyond transcript profiling and genotype analysis
Journal:Nature Reviews Genetics 7, 200-210 (2006); doi:10.1038/nrg1809
Understanding complex functional mechanisms requires the global and parallel analysis of different cellular processes. DNA microarrays have become synonymous with this kind of study and, in many cases, are the obvious platform to achieve this aim. They have already made important contributions, most notably to gene-expression studies, although the true potential of this technology is far greater. Whereas some assays, such as transcript profiling and genotyping, are becoming routine, others are still in the early phases of development, and new areas of application, such as genome-wide epigenetic analysis and on-chip synthesis, continue to emerge.
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Article
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Assaying chromosomal inversions by single-molecule haplotyping
Journal:Nature Methods 3, 439-445 (2006); doi:10.1038/nmeth881
Inversions are an important form of structural variation, but they are difficult to characterize, as their breakpoints often fall within inverted repeats. We have developed a method called 'haplotype fusion' in which an inversion breakpoint is genotyped by performing fusion PCR on single molecules of human genomic DNA. Fusing single-copy sequences bracketing an inversion breakpoint generates orientation-specific PCR products, exemplified by a genotyping assay for the int22 hemophilia A inversion on Xq28. Furthermore, we demonstrated that inversion events with breakpoints embedded within long (>100 kb) inverted repeats can be genotyped by haplotype-fusion PCR followed by bead-based single-molecule haplotyping on repeat-specific markers bracketing the inversion breakpoint. We illustrate this method by genotyping a Yp paracentric inversion sponsored by >300-kb-long inverted repeats. The generality of our methods to survey for, and genotype chromosomal inversions should help our understanding of the contribution of inversions to genomic variation, inherited diseases and cancer.
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