Comparison of the experimental methods in haplotype sequencing via next generation sequencing

Abstract

Although the diploid nature has been observed for over 50 years, phasing the diploid is still a laborious task. The speed and throughput of next generation sequencing have largely increased in the past decades. However, the short read-length remains one of the biggest challenges of haplotype analysis. For instance, reads as short as 150 bp span no more than one variant in most cases. Numerous experimental technologies have been developed to overcome this challenge. Distance, complexity and accuracy of the linkages obtained are the main factors to evaluate the efficiency of whole genome haplotyping methods. Here, we review these experimental technologies, evaluating their efficiency in linkages obtaining and system complexity. The technologies are organized into four categories based on its strategy: (i) chromosomes separation, (ii) dilution pools, (iii) crosslinking and proximity ligation, (ix) long-read technologies. Within each category, several subsections are listed to classify each technology. Innovative experimental strategies are expected to have high-quality performance, low cost and be labor-saving, which will be largely desired in the future.

Graphical abstract

Keywords

next generation sequencing / haplotyping / haplotype sequencing

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ACKNOWLEDGEMENTS

This work was supported by the National Basic Research Program of China (No. 2012CB316501), and the National Natural Science Foundation of China (Nos. 61227803 and 61571121).

COMPLIANCE WITH ETHICS GUIDELINES

The authors Jing Tu, Na Lu, Mengqin Duan, An Ju, Xiao Sun and Zuhong Lu declare they have no conflict of interests.

This article does not contain any studies with human or animal subjects performed by any of the authors.

Funding

RIGHTS & PERMISSIONS

2016 Higher Education Press and Springer-Verlag Berlin Heidelberg