Advantages And Disadvantages Of Snps

SNPs are appealing to the forensic DNA community for several reasons. First and foremost, the polymerase chain reaction (PCR) products from SNPs can be less than 100 bp in size, which means that these markers would be able to withstand degraded DNA samples better than STRs that have amplicons as large as

Characteristics

Short Tandem Repeats (STRs)

Single Nucleotide Polymorphisms (SNPs)

Occurrence in human genome General informativeness Marker type

Number of alleles per marker Detection methods Multiplex capability

Major advantage for forensic application

~1 in every 15 kb High

Di-, tri-, tetra-, pentanucleotide repeat markers with many alleles

Typically > 5

Gel/capillary electrophoresis

> 10 markers with multiple fluorescent dyes

Many alleles enabling higher success rates for detecting and deciphering mixtures

Low; only 20-30% as informative as STRs

Mostly bi-allelic markers with six possibilities: A/G, C/T, A/T, C/G, T/G, A/C

Typically 2

Sequence analysis; microchip hybridization Potential of 1000s on microchip

PCR products can be made small potentially enabling higher success rates with degraded DNA samples

300-400 bp (see Chapter 7). Second, they can be potentially multiplexed to a higher level than STRs. Third, the sample processing and data analysis may be more fully automated because a size-based separation is not needed. Fourth, there is no stutter artifact associated with each allele, which should help simplify interpretation of the allele call. Finally, the ability to predict ethnic origin and certain physical traits may be possible with careful selection of SNP markers.

The vast majority of SNPs are bi-allelic meaning that they have two possible alleles and therefore three possible genotypes. For example, if the alleles for a SNP locus are A and B, then the three possible genotypes would be AA, BB, or AB. Mixture interpretation can present a challenge with SNPs because it may be difficult to tell the difference between a true heterozygote and a mixture containing two homozygotes or a heterozygote and a homozygote. The ability to obtain quantitative information from SNP allele calls is important when attempting to decipher mixtures (Gill 2001).

One of the biggest challenges at this time to using SNPs in forensic DNA typing applications is the inability to simultaneously amplify enough SNPs in robust multiplexes from low amounts of DNA. Because a single bi-allelic SNP by itself yields less information than a multi-allelic STR marker, it is necessary to analyze a larger number of SNPs in order to obtain a reasonable power of discrimination to define a unique profile. Progress is being made in the area of multiplex PCR amplification but as of January 2004 the best result so far is a 35plex with Y chromosome SNPs (Sanchez et al. 2003).

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