CS Mukhopadhyay and RK Choudhary
School of Animal Biotechnology, GADVASU, Ludhiana
SYBR is a fluorophore that illuminates green after binding to double‐stranded DNA at the minor grooves. It is used in quantitative PCR (qPCR) to determine the amount of amplicon generated following each cycle of amplification. As real‐time PCR is very sensitive, and the presence of secondary structures and spurious amplicon would inflate the quantified amplicon, adequate care should be exercised while designing very specific and high‐quality primers for the SYBR Green chemistry of qPCR.
TABLE 20.1 Optimal and permissible ranges of parameters of qPCR primers (SYBR green chemistry).
SN | Feature | Optimal | Limits | Pros and cons |
1 | Length of each primer | 21–23 nt | 18–25 nt | Shorter primers could increase mispriming, and longer primers would reduce efficiency. |
2 | Amplicon | 120–200 bp | 100–220 bp | Primers for qPCR using chemistry other than SYBR Green use shorter amplicon (60–150 bp). |
3 | Primer Tm | 64 °C | 58–67 °C | Difference between the Tm of two primers should not be more than 2 °C. |
4 | Annealing temperature | 60 °C | 57–64 °C | The annealing and extension temperature of the Taq is recommended to be same. |
5 | GC% of primer | 55–65% | 35–80% | Higher or lower GC% would affect Tm of primers. |
6 | GC‐clamp at 3’‐end | 1 clamp | Maximum 2 clamps | More than 2 G/C clamp with the last five bases at 3’‐end will make the primers sticky. |
7 | Run of identical bases | 2 bases | Maximum 4 | This will increase the possibility of secondary structure formation. |
8 | Proportion of different bases | Equal percentage of each base | Minimum 20–30% of one base | __ |
9 | 3’‐end stability of primers | Delta G > = –9 kcal/mol | –7 to –11 kcal/mol | Delta G of last five bases at 3’‐end should be higher (ignoring the symbol) than that of the internal region of the primer. |
10 | Concentration of Mg++ | 3–4 mM of MgCl2 | 3–6 mM | SYBR green buffer itself contains appropriate amount of MgCl2. |
11 | Max repeat mispriming | 12 or more | 11–15 | Larger value inversely proportionate to the probability of repeat mispriming of the primers. |
12 | Check for template mispriming | No mispriming | Do not select primers with template mispriming | Run Primer‐Blast of NCBI to identify the possible mispriming in the same species. |
13 | Number of unknown bases | 0 | 0 | No non‐specific bases should be present, to prevent non‐specific amplification. |
14 | Run of the same base | 2 | 2–4 | Run of the same base will increase the mispriming. |
15 | Checking the primer quality | Delta G values should be higher for primer‐template and lower for primer secondary structures | Identify potential hairpins and primer‐dimer/self‐dimer formation. |
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