Screening South African familial adenomatous polyposis families for the five-nucleotide deletion at codon 1309 of the APC gene

doi:10.1016/S0890-8508(95)91007-7

Molecular and Cellular Probes

Volume 9, Issue 1, February 1995, Pages 49-51

https://doi.org/10.1016/S0890-8508(95)91007-7 Get rights and content

We report the occurrence of a common five-nucleotide deletion at codon 1309 of the adenomatous polyposis coli (APC) gene in four different South African population groups. The mutation causes familial adenomatous polyposis (FAP) in 18% (4/22 unrelated patients screened) of affected South Africans, which is similar to the frequency described in several other populations. Knowledge of the gene mutation underlying FAP enabled conclusive genetic testing of at-risk family members of four index patients in which this specific mutation has been characterized. The non-radioactive heteroduplex method described in this study allowed cost-effective molecular diagnosis directly after electrophoresis of enzymatically-amplified DNA in agarose gels. The resulting reduction of uncertainty for at-risk relatives is an important benefit of diagnosis at the DNA level.

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Citation Excerpt :
The enhanced specificity through deliberate multiple base-pair mismatch between primer–template is expected to enhance AS-PCR for the detection of some biomarkers. Although many genetic diseases are associated with short deletion or insertion mutations [15–25], the application of AS-PCR for analysis of theses short deletions or insertions is still rare. To the best of our knowledge, in literature, only several clinical analysis such as the cystic fibrosis F508 deletion [11,42], Sjögren–Larsson syndrome [43], and ABO genotyping [44] have been reliably detected by AS-PCR.
Allele-specific PCR (AS-PCR) has been widely used for the detection of single nucleotide polymorphism. But there are some challenges in using AS-PCR for specifically detecting DNA variations with short deletions or insertions. The challenges are associated with designing selective allele-specific primers as well as the specificity of AS-PCR in distinguishing some types of single base-pair mismatches. In order to address such problems and enhance the applicability of AS-PCR, a general primer design method was developed to create a multiple base-pair mismatch between the primer 3′-terminus and the template DNA. This approach can destabilize the primer–template complex more efficiently than does a single base-pair mismatch, and can dramatically increase the specificity of AS-PCR. As a proof-of-principle demonstration, the method of primer design was applied in colony PCR for identifying plasmid DNA deletion or insertion mutants after site-directed mutagenesis. As anticipated, multiple base-pair mismatches achieved much more specific PCR amplification than single base-pair mismatches. Therefore, with the proposed primer design method, the detection of short nucleotide deletion and insertion mutations becomes simple, accurate and more reliable.
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Original articleScreening South African familial adenomatous polyposis families for the five-nucleotide deletion at codon 1309 of the APC gene

Cell

Cell

Lancet

Gastroenterology

Genomics

Lancet

The concept of hereditary colorectal cancer and the implications of its study

Identification of FAP locus genes from chromosome 5q21

Science

Original article
Screening South African familial adenomatous polyposis families for the five-nucleotide deletion at codon 1309 of the APC gene