Haplotype-resolved Genome Sequencing: Experimental Methods and Applications

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2015 May 8

PMID 25948246

Citations 103

Authors

Matthew W Snyder

Andrew Adey

Jacob O Kitzman

Jay Shendure

Affiliations

Soon will be listed here.

Abstract

Human genomes are diploid and, for their complete description and interpretation, it is necessary not only to discover the variation they contain but also to arrange it onto chromosomal haplotypes. Although whole-genome sequencing is becoming increasingly routine, nearly all such individual genomes are mostly unresolved with respect to haplotype, particularly for rare alleles, which remain poorly resolved by inferential methods. Here, we review emerging technologies for experimentally resolving (that is, 'phasing') haplotypes across individual whole-genome sequences. We also discuss computational methods relevant to their implementation, metrics for assessing their accuracy and completeness, and the relevance of haplotype information to applications of genome sequencing in research and clinical medicine.

Citing Articles

Single chromatin fiber profiling and nucleosome position mapping in the human brain.

Peter C, Agarwal A, Watanabe R, Kassim B, Wang X, Lambert T Cell Rep Methods. 2024; 4(12):100911.

PMID: 39631398 PMC: 11704683. DOI: 10.1016/j.crmeth.2024.100911.

Somatic mutation phasing and haplotype extension using linked-reads in multiple myeloma.

Foltz S, Li Y, Yao L, Terekhanova N, Weerasinghe A, Gao Q bioRxiv. 2024; .

PMID: 39149342 PMC: 11326269. DOI: 10.1101/2024.08.09.607342.

Genome-wide association study for cashmere traits in Inner Mongolia cashmere goat population reveals new candidate genes and haplotypes.

Rong Y, Wang X, Na Q, Ao X, Xia Q, Guo F BMC Genomics. 2024; 25(1):658.

PMID: 38956486 PMC: 11218406. DOI: 10.1186/s12864-024-10543-4.

otb: an automated HiC/HiFi pipeline assembles the Prosapia bicincta Genome.

Molik D, Stahlke A, Sharma S, Simmonds T, Corpuz R, Kauwe A G3 (Bethesda). 2024; 14(8).

PMID: 38861413 PMC: 11304988. DOI: 10.1093/g3journal/jkae129.

Technology-enabled great leap in deciphering plant genomes.

Xie L, Gong X, Yang K, Huang Y, Zhang S, Shen L Nat Plants. 2024; 10(4):551-566.

PMID: 38509222 DOI: 10.1038/s41477-024-01655-6.

References

Drysdale C, McGraw D, Stack C, Stephens J, Judson R, Nandabalan K . Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci U S A. 2000; 97(19):10483-8. PMC: 27050. DOI: 10.1073/pnas.97.19.10483. View

Nedelkova M, Maresca M, Fu J, Rostovskaya M, Chenna R, Thiede C . Targeted isolation of cloned genomic regions by recombineering for haplotype phasing and isogenic targeting. Nucleic Acids Res. 2011; 39(20):e137. PMC: 3203589. DOI: 10.1093/nar/gkr668. View

Aguiar D, Istrail S . Haplotype assembly in polyploid genomes and identical by descent shared tracts. Bioinformatics. 2013; 29(13):i352-60. PMC: 3694639. DOI: 10.1093/bioinformatics/btt213. View

Voskoboynik A, Neff N, Sahoo D, Newman A, Pushkarev D, Koh W . The genome sequence of the colonial chordate, Botryllus schlosseri. Elife. 2013; 2:e00569. PMC: 3699833. DOI: 10.7554/eLife.00569. View

Wang J, Fan H, Behr B, Quake S . Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell. 2012; 150(2):402-12. PMC: 3525523. DOI: 10.1016/j.cell.2012.06.030. View

Chaisson M, Huddleston J, Dennis M, Sudmant P, Malig M, Hormozdiari F . Resolving the complexity of the human genome using single-molecule sequencing. Nature. 2014; 517(7536):608-11. PMC: 4317254. DOI: 10.1038/nature13907. View

Yang W, Hormozdiari F, Wang Z, He D, Pasaniuc B, Eskin E . Leveraging reads that span multiple single nucleotide polymorphisms for haplotype inference from sequencing data. Bioinformatics. 2013; 29(18):2245-52. PMC: 3753566. DOI: 10.1093/bioinformatics/btt386. View

Xiao M, Wan E, Chu C, Hsueh W, Cao Y, Kwok P . Direct determination of haplotypes from single DNA molecules. Nat Methods. 2009; 6(3):199-201. PMC: 3880790. DOI: 10.1038/nmeth.1301. View

Turner D, Shendure J, Porreca G, Church G, Green P, Tyler-Smith C . Assaying chromosomal inversions by single-molecule haplotyping. Nat Methods. 2006; 3(6):439-45. PMC: 2690135. DOI: 10.1038/nmeth881. View

10.

Douglas J, Boehnke M, Gillanders E, Trent J, Gruber S . Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies. Nat Genet. 2001; 28(4):361-4. DOI: 10.1038/ng582. View

11.

Lo C, Liu R, Lee J, Robasky K, Byrne S, Lucchesi C . On the design of clone-based haplotyping. Genome Biol. 2013; 14(9):R100. PMC: 4053695. DOI: 10.1186/gb-2013-14-9-r100. View

12.

Lo Y, Chan K, Sun H, Chen E, Jiang P, Lun F . Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med. 2010; 2(61):61ra91. DOI: 10.1126/scitranslmed.3001720. View

13.

Lieberman-Aiden E, van Berkum N, Williams L, Imakaev M, Ragoczy T, Telling A . Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009; 326(5950):289-93. PMC: 2858594. DOI: 10.1126/science.1181369. View

14.

McKernan K, Peckham H, Costa G, McLaughlin S, Fu Y, Tsung E . Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res. 2009; 19(9):1527-41. PMC: 2752135. DOI: 10.1101/gr.091868.109. View

15.

Zong C, Lu S, Chapman A, Xie X . Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science. 2012; 338(6114):1622-6. PMC: 3600412. DOI: 10.1126/science.1229164. View

16.

Browning S, Browning B . Haplotype phasing: existing methods and new developments. Nat Rev Genet. 2011; 12(10):703-14. PMC: 3217888. DOI: 10.1038/nrg3054. View

17.

Xie W, Barr C, Kim A, Yue F, Lee A, Eubanks J . Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell. 2012; 148(4):816-31. PMC: 3343639. DOI: 10.1016/j.cell.2011.12.035. View

18.

Laszlo A, Derrington I, Ross B, Brinkerhoff H, Adey A, Nova I . Decoding long nanopore sequencing reads of natural DNA. Nat Biotechnol. 2014; 32(8):829-33. PMC: 4126851. DOI: 10.1038/nbt.2950. View

19.

Abecasis G, Auton A, Brooks L, DePristo M, Durbin R, Handsaker R . An integrated map of genetic variation from 1,092 human genomes. Nature. 2012; 491(7422):56-65. PMC: 3498066. DOI: 10.1038/nature11632. View

20.

Regan J, Kamitaki N, Legler T, Cooper S, Klitgord N, Karlin-Neumann G . A rapid molecular approach for chromosomal phasing. PLoS One. 2015; 10(3):e0118270. PMC: 4349636. DOI: 10.1371/journal.pone.0118270. View