SALSA MLPA P378 MUTYH probemix - 100 reactions

application: Colon cancer, stomach cancer (hereditary)

region: 1p34 and 15q1 Detailní informace

Cena s DPH € 1 147.08
Cena bez DPH € 948.00
 100 react
Dostupnost Skladem
Kód produktu P378-100R

Nejnovější informace o produktu naleznete exklusivně na stránkách výrobce MRC-Holland (nové okno)

Detailní popis SALSA MLPA P378 MUTYH probemix - 100 reactions

P378-025R SALSA MLPA P378 MUTYH probemix – 100 rxn

SD027 Artificial Duplication DNA: MRC-Holland has prepared a mixture of female genomic DNA from healthy individuals and a carefully titrated amount of plasmid that contains the target sequence recognised by several probes present in the selected MLPA probemixes. The use of SD027 in MLPA reactions performed with the selected MLPA probemixes will therefore show a duplication of several sequences. This SD027 can be ordered separately.

The MUTYH (mutY homolog (E. coli)) gene encodes a DNA glycosylase involved in oxidative DNA damage repair. Mutations in this gene result in heritable predisposition to colon and stomach cancer (MUTYH associated polyposis). MUTYH related colorectal cancer should be regarded as an autosomal recessive trait. A single defective copy of the MUTYH gene may result in no, or only a small increase in risk for colorectal cancer. Bi-allelic MUTYH defects however impart a 93-fold excess risk of colorectal cancer with an almost complete penetrance by the age of 60 years (Farrington SM et al. 2005, Am J Hum Genet. 77:112-9). Bi-allelic MUTYH-related colorectal cancer presents 36% of the cases without polyps. The two most common MUTYH mutations associated with hereditary colorectal cancer are p.Y179C (c.536A>G) and p.G396D (c.1187G>A). These two mutations cover up to 80% of germline alterations found in patients of European origin (Aretz S and Hes FJ, 2010, Eur J Hum Genet. 18(9)). Patients with homozygous G396D or heterozygous G396D/Y179C mutations show a milder phenotype when compared to homozygous carriers of the Y179C mutation (Nielsen M et al. 2009, Gastroenterology. 136:471-6).

Hereditary mixed polyposis syndrome (HMPS) is characterized by autosomal dominant inheritance of multiple types of colorectal polyps and development of colorectal cancer at later age. It has been shown that HMPS is caused by a 40 kb duplication of the 3’ end of the SCG5 (secretogranin V) gene and the upstream region of the GREM1 locus. This duplication leads to increased allele-specific GREM1 expression in the epithelium of the large bowel in individuals with HMPS. Increased GREM1 expression is predicted to cause reduced bone morphogenetic protein pathway activity, a mechanism also underlying tumorigenesis in juvenile polyposis (Jaeger E et al. 2012, Nat Genet. 44:699-703).

The MUTYH gene (16 exons) spans ~11 kb of genomic DNA and is located at 1p34.1, 45 Mb from the p-telomere. The GREM1 gene (2 exons) spans ~17 kb of genomic DNA and is located at 15q13.3. The SCG5 gene (6 exons) spans ~56 kb of genomic DNA and is located next to GREM1 also at 15q13.3. The P378-C1 probemix contains one probe for each exon of the MUTYH gene. Furthermore, it also contains mutation-specific probes for the Y179C and G396D point mutations. For GREM1, two probes for each exon are included, and in addition, two probes for the region upstream of the GREM1 gene are included. For SCG5, probes for exons 2 to 6 are present. In addition, 14 reference probes have been included in this probemix, detecting different autosomal chromosomal locations which are relatively quiet in colorectal and stomach cancer.

SD022 Sample DNA: Please note that the Y179C and G396D mutation-specific probes have only been tested on control plasmids and not on positive human DNA samples! This SD022 sample DNA is provided with each P378-C1 probemix vial and can be used in data binning in the fragment analysis and as a positive control for the mutation-specific probes.

This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned genes in a DNA sample and to detect the presence of the aforementioned mentioned point mutations in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in these genes are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test, except for the MUTYH Y179C and G396D point mutations.

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