Review
Applications of single nucleotide polymorphisms in crop genetics

https://doi.org/10.1016/S1369-5266(02)00240-6Get rights and content

Abstract

The discovery of single nucleotide polymorphisms (SNPs) and insertions/deletions, which are the basis of most differences between alleles, has been simplified by recent developments in sequencing technology. SNP discovery in many crop species, such as corn and soybean, is relatively straightforward because of their high level of intraspecific nucleotide diversity, and the availability of many gene and expressed sequence tag (EST) sequences. For these species, direct readout of SNP haplotypes is possible. Haplotype-based analysis is more informative than analysis based on individual SNPs, and has more power in analyzing association with phenotypes. The elite germplasm of some crops may have been subjected to bottlenecks relatively recently, increasing the amount of linkage disequilibrium (LD) present and facilitating the association of SNP haplotypes at candidate gene loci with phenotypes. Whole-genome scans may help identify genome regions that are associated with interesting phenotypes if sufficient LD is present. Technological improvements make the use of SNP and indel markers attractive for high-throughput use in marker-assisted breeding, EST mapping and the integration of genetic and physical maps.

Introduction

As more genomes, including those of humans, Arabidopsis and soon rice, are completely sequenced, interest is re-focusing on the discovery and analysis of intraspecific sequence differences. This is particularly evident in research into the human genome, in which over one million single nucleotide polymorphisms (SNPs) (the most common type of sequence differences between alleles) have been catalogued recently. These polymorphisms could be used as simple genetic markers, which may be identified in the vicinity of virtually every gene. There is also great potential for the use of SNPs in the detection of associations between allelic forms of a gene and phenotypes, especially for common diseases that have multifactorial genetics 1., 2.. Very recently, studies of the level of linkage disequilibrium (LD) in human populations revealed that large islands of high LD extend over much larger distances than predicted previously [3••]. This finding suggests that the analysis of SNP haplotypes, rather than of individual SNPs, provides a more effective way of associating alleles with traits.

When working with SNPs, plant scientists could take advantage of the investment in technology development that has already been made by the broader community, especially by the Human Genome Project. Considerable progress has been made in the areas of SNP discovery and SNP assay development, and in the use of haplotype diversity for association mapping. At the same time, plant genomes offer some unique advantages for researchers using SNP-based technologies. The high level of polymorphism of many plant species, such as maize, facilitates SNP identification. Inbred lines, when available, enable direct read-off of haplotypes. Populations that are suitable for high-resolution genetic mapping make the detailed analysis of the relationship between genetic and physical distance relatively straightforward.

In an accompanying review, Buckler and Thornsberry (this issue) discuss recent advances in understanding sequence diversity in higher plants and the factors that influence diversity distribution. Here, we focus on the methodology of SNP discovery, the applications of SNPs in plant genetics and breeding, and some of the implications of recent advances in human association studies for work on higher plants.

Section snippets

SNP discovery

Several different routes to the discovery of SNPs may be taken. These include the re-sequencing of PCR amplicons with or without pre-screening; electronic SNP (eSNP) discovery in shotgun genomic libraries; and eSNP discovery in expressed sequence tag (EST) libraries.

Direct sequencing of DNA segments (amplified by PCR) from several individuals is the most direct way to identify SNP polymorphisms 4., 5.. PCR primers are designed to amplify 400–700 bp segments of DNA, which are frequently derived

SNP assays

Several methods are available for SNP genotyping, which have already been discussed in several reviews 23•., 24•., 25., 26., 27.. The choice of a method for a particular assay depends on many factors, including cost, throughput, equipment needed, difficulty of assay development, and potential for multiplexing. There is intense commercial activity in this area and no dominant assay has emerged yet. Marker-assisted breeding of soybean in a commercial setting has been facilitated by the use of a

SNPs and indels as genetic markers

Numerous types of DNA markers that are based on the indirect detection of sequence-level polymorphism have been developed 28., 29.. Frequently, highly informative simple sequence repeat (SSR) markers are preferred [30]. SSRs are less suitable for association studies, however, because of the occurrence of homoplasy; that is, the occurrence of SSR alleles of identical size but different evolutionary origin 31., 32.. Conversely, it is also likely that SSRs of different size are embedded in

Conclusions

Single nucleotide polymorphisms and indels are an essentially inexhaustible source of polymorphic markers for use in the high-resolution genetic mapping of traits, and for association studies that are based on candidate genes or possibly whole genomes. A better understanding of the distribution of LD and of recombination frequencies along plant chromosomes is needed, especially in crop plants. Much may be learned from the recent progress in this area in human and animal genomics. The rapid

Acknowledgements

I would like to thank Michele Morgante and Ed Buckler for helpful suggestions. Ada Ching and Kelly Palaisa supplied some unpublished data.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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