Genotyping

Genotyping studies are those which identify differences in the DNA sequence (i.e genotype) of a sample. The genomic DNA samples are often obtained from two contrasting groups of samples, e.g. drought-resistant rice cultivars vs. drought-sensitive counterparts, with the aim of identifying differences in the genotype which may explain the difference in phenotype.

Genotyping studies can be designed to identify DNA sequence differences at three levels:

• Single nucleotide polymorphisms (SNPs, pronounced ‘snips’): SNP analysis focuses on differences in the DNA sequence at the single nucleotide level.
  • Example: SNP 6.0 profiling of plasma DNA in breast cancer patients
• Copy number variations (CNVs): CNVs refer to an increase or decrease in the number of copies of a segment of DNA (e.g. a gene, or a locus-specific DNA repeat element). Each ‘copy’ can be as short as 50 bases or up to 100 kilobases.
  • Example: A genome-wide copy number variant study of suicidal behaviour
• Structural variations: they are an order of magnitude larger than CNVs and often cover megabases of DNA, and can be caused by chromosomal rearrangement events.
  • Example: Transcription profiling by high throughput sequencing of different maize lines to discover and characterise ‘presence-absence variation’ in the maize genome

One common extension of genotyping studies in humans are genome-wide association studies (GWAS). Samples from cases (e.g. rheumatoid arthritis patients) and controls (e.g. healthy individuals) are genotyped across specific sites in the genome, followed by statistical analysis to find SNPs which are significantly more prevalent in one group (e.g. the disease cases). Such SNPs may then suggest an association between the SNPs and disease susceptibility.