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Some of the more common problems that can occur during genomic DNA preparation are described in Table 4.4. Refer to the instructions provided with your genomic DNA preparation product for more detailed troubleshooting information.

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Problem	Possible cause	Solution
Quality of genomic DNA is poor (genomic DNA is not high molecular weight or looks degraded)	Starting sample was not stored properly. \r\n \r\n \r\nStarting sample was fixed with formalin or another fixative (e.g., FFPE tissue). \r\n \r\nPurified genomic DNA was not stored properly. \r\n	Nucleases may have degraded genomic DNA. Follow recommendations for storage and handling of your sample type. \r\n \r\nGenomic DNA may be fragmented in the sample. It is not possible to obtain high-molecular-weight DNA from this sample type. \r\n \r\n \r\nFollow recommended storage conditions to minimize degradation by nucleases. Do not store DNA in water for extended periods.
DNA yield is low	If the yield is low and purity/quality is good: Starting sample size was insufficient. \r\n \r\nIf yield and purity/quality are low: \r\nStarting sample was not stored properly. \r\n \r\nCells were not lysed thoroughly.	Limited samples such as buccal swabs, FTA/Guthrie card blood, etc. may require amplification of genomic DNA using Phi29 DNA polymerase. \r\n \r\n \r\nNucleases may have degraded genomic DNA. Follow recommendations for storage and handling of your sample type. \r\n \r\n \r\nFollow homogenization/lysis recommendations for your sample type. \r\n \r\n
A₂₆₀/A₂₈₀ of genomic DNA sample is < 1.7 or > 1.9	A₂₆₀/A₂₈₀ < 1.7: Proteins or chaotropes may be present. \r\nA₂₆₀/A₂₈₀ > 1.9: RNA may be present.	Process starting sample according to recommended instructions to ensure thorough removal of proteins. Do NOT overload the purification system. To remove protein contaminants, treat the sample with a protease or perform a phenol extraction + ethanol precipitation. \r\nEnsure wash steps are followed closely to eliminate carryover of contaminants into your final sample. \r\nFollow recommendations for processing different sample types. Some sample types contain high levels of RNA. RNA may not interfere with some applications.
DNA does not work well in downstream application	Genomic DNA quality is poor. \r\n \r\nIf DNA quality is good: Contaminants (lipids, salts, etc.) may be present in the sample. \r\n \r\nFor silica purification using ethanolic wash buffer: \r\nResidual ethanol remains in the sample.	See troubleshooting tips above for poor-quality genomic DNA. \r\n \r\nDo not overload the purification system. This may result in poor yield and/or decreased purity of genomic DNA. \r\nIf organic solvents such as phenol were used, residual solvent may be present in the sample. Precipitate the DNA with salt and alcohol. (Appendix 4.) \r\n \r\n \r\n \r\nBe sure to thoroughly air dry the sample prior to elution. \r\n

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