Method, kit and specific primer for detecting CLCN1 (chloride channel 1) gene mutation
A specific and kit-based technology used in the detection of coding region and intron splice site mutations of CLCN1 gene
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Embodiment 1
[0032] Example 1: Design of specific primers
[0033] Design amplification primers according to the characteristics of CLCN1 exon distribution:
[0034] 1) According to the reference sequence of CLCN1 normal gene in NCBI and other databases, design primers of 15-30 BP according to the principle of complementary base pairing at the upstream of the 5' end and downstream of the 3' end of the mutation site. The primers should be designed in the conserved region of the nucleic acid series and have specificity;
[0035] 2) The product cannot form a secondary structure, the bases should be randomly distributed, and the primer itself cannot have 4 consecutive bases complementary;
[0036] 3) Design primers for 40-50bp extensions at both ends of each exon, including intron splicing sites (including mutation sites, which can cause frame-shift mutations).
[0037] 4) The annealing temperature difference between forward and reverse primers of all PCR fragments shall not exceed 5°C, and ...
Embodiment 2
[0041] Embodiment 2: sample DNA extraction
[0042] The positive sample used in the present invention is from a subject from Shandong, who was diagnosed as congenital myotonia by a hospital, sporadic cases without family history, and obtained blood samples after informed consent.
[0043] The QIAamp DNA Blood MINI Kit kit (Cat. No. 51106) from QIAGEN was used to extract DNA from the whole blood sample of the subjects. Exemplary steps are as follows:
[0044] (1) Add 20 μl proteinase K to a 1.5ml centrifuge tube;
[0045] (2) Add 200 μl whole blood sample to the centrifuge tube;
[0046] (3) Add 200 μl buffer AL to the centrifuge tube, and vortex for 15 seconds;
[0047] (4) 56 ° water bath for 15 minutes;
[0048] (5) Centrifuge properly so that all the liquid falls to the bottom of the centrifuge tube;
[0049] (6) Add 200 μl of absolute ethanol to the centrifuge tube, shake for 15 seconds to mix, and centrifuge properly to make all the liquid drop to the bottom of the c...
Embodiment 3
[0057] Embodiment 3: PCR amplification
[0058] The DNA sample extracted in Example 2 was amplified using the PCR amplification primer pair designed in Example 1, and the reaction used a 25 μl system, wherein: enzymes and buffer solutions were purchased from KATARA Company.
[0059]
[0060] The PCR conditions are:
[0061] Pre-denaturation at 95°C for 5 minutes
[0062] 94℃30sec→specific annealing temperature 30sec→72℃30sec (35 cycles)
[0063] Then extend for another 10 minutes.
[0064] Wherein, the specific annealing temperature of each pair of primers is as follows:
[0065]
[0066]
PUM
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