HAPPY Mapping

Abstract

For large genomes, such as most eukaryotes, it is difficult or impossible to produce a complete, gap‐free genome sequence. Genome mapping entails finding the relative positions of different deoxyribonucleic acid (DNA) sequences in such an incompletely sequenced genome, often across large distances (kb or Mb). An accurate genome map arranges sequence fragments in context, and can also be used to guide directed sequencing efforts to close the remaining gaps. HAPPY mapping is a versatile in vitro method for making such genome maps. Genomic DNA is broken randomly and diluted to the point where samples contain only a few molecules. Many such samples are analysed and, if two sequences (markers) are often found together in the same sample, this implies that they are often on the same DNA fragment and therefore adjacent in the genome.

Key Concepts

  • A genome map shows the positions of different DNA sequences in a genome, even if the genome has not been fully sequenced.
  • Genome maps show the large‐scale organisation of the genome, across many kilobases or megabases.
  • Genome maps can help to guide efforts to close in a full genome sequence, by showing the size and position of remaining gaps.
  • HAPPY mapping relies only on in vitro steps, and is less prone to artefacts than some other mapping methods
  • HAPPY mapping can be used to make maps with resolutions from kilobases to hundreds of kilobases.

Keywords: genome mapping; single‐molecule analysis; linkage analysis; polymerase chain reaction; genome sequencing

Figure 1. Principle of HAPPY mapping. The example shows the mapping of just three sequence‐tagged site (STS) markers (A, B and Z), although typically many hundreds are mapped in parallel. Genomic deoxyribonucleic acid (DNA) is prepared from cells (a), and is broken randomly to give a pool of fragments (b). The fragments are dispensed into a series of samples (c) constituting the mapping panel; each sample contains less than a genome's worth of fragments and hence only a subset of the markers. Polymerase chain reaction (PCR) is used to ascertain which markers are present in each member of the panel (d). Linked markers such as A and B, because they tend to lie on the same DNA fragments after breakage, tend to cosegregate (as in samples 1, 3 and 96 of this mapping panel). Cosegregation frequencies reflect the distances between markers, which allow a map (e) to be deduced.
close

References

Abrahamsen MS, Templeton TJ, Enomoto S, et al (2004) Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 304: 441–445.

Dear PH and Cook PR (1989) HAPPY mapping – a proposal for linkage mapping the human genome. Nucleic Acids Research 17: 6795–6807.

Dear PH and Cook PR (1993) HAPPY mapping – linkage mapping using a physical analog of meiosis. Nucleic Acids Research 21: 13–20.

Dear PH (1997) HAPPY Mapping in Genome Mapping: A Practical Approach, pp. 95–123. Oxford, UK: IRL Press.

Dear PH, Bankier AT and Piper MB (1998) A high‐resolution metric HAPPY map of human chromosome 14. Genomics 48: 232–241.

Eichinger L, Pachebat JA, Glöckner G, et al. (2005) The genome of the social amoeba Dictyostelium discoideum. Nature 435: 43–57.

Hamilton EP, Dear PH, Rowland T, et al. (2006) Use of HAPPY mapping for higher order assembly of the Tetrahymena genome. Genomics 88: 443–451.

Konfortov BA, Cohen HM, Bankier AT and Dear PH (2000) A high‐resolution HAPPY map of Dictyostelium discoideum chromosome 6. Genome Research 10: 1737–1742.

Lim LS, Tay YL, Alias H, Wan KL and Dear PH (2012) Insights into the genome structure and copy‐number variation of Eimeria tenella. BMC Genomics 13: 389.

Newell WR, Mott R, Beck S and Lehrach H (1995) Construction of genetic maps using distance geometry. Genomics 30: 59–70.

Piper MB, Bankier AT and Dear PH (1999) A HAPPY map of Cryptosporidium parvum. Genome Research 8: 1299–1307.

Shirley MW, Ivens A, Gruber A, et al. (2004) The Eimeria genome projects: a sequence of events. Trends in Parasitology 20: 199–201.

Zhang L, Cui XF, Schmitt K, et al. (1992) Whole genome amplification from a single cell: implications for genetic analysis. Proceedings of the National Academy of Sciences of the United States of America 89: 5847–5851.

Further Reading

Cox DR, Burmeister M, Price ER, Kim S and Myers RM (1990) Radiation hybrid mapping: a somatic cell genetic method for constructing high‐resolution maps of mammalian chromosomes. Science 250: 245–250.

Ott J, Wang J and Leal SM (2015) Genetic linkage analysis in the age of whole‐genome sequencing. Nature Reviews Genetics 16: 275–284.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Dear, Paul H(Apr 2018) HAPPY Mapping. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005362.pub2]