Úvod Reagencie Basic research SALSA MLPA ME031 GNAS probemix - 50 reactions

SALSA MLPA ME031 GNAS probemix - 50 reactions

application: Albright hereditary osteodystrophy (AHO), Pseudohypoparathyroidism (PHP)
region: GNAS 20q13.32 Detailní informace

Cena s DPH € 573.54
Cena bez DPH € 474.00
 50 react
Dostupnost Na dotaz
Kód produktu ME031-050R

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

Detailní popis SALSA MLPA ME031 GNAS probemix - 50 reactions

ME031-050R SALSA MLPA ME031 GNAS probemix – 50 rxn

Albright hereditary osteodystrophy (AHO) is a complex dysmorphology and endocrine syndrome characterised by short stature, round face, brachymetacarpia, subcutaneous ossification and various degrees of neurobehavioral defects and developmental delay. It is caused by heterozygous inactivating GNAS mutations. Some patients suffer from hormone resistance, mainly parathyroid hormone, leading to hypocalcemia, hyperphosphatemia, high plasma PTH levels and obesity and their condition is referred to as pseudohypoparathyroidism (PHPIa). AHO in the absence of hormone resistance is called pseudopseudohypoparathyroidism (PPHP). In addition to PHPIa and PPHP, aberrations in the GNAS locus can cause PHPIb, which refers to cases in which some of the endocrine disturbances found in PHPIa occur in the absence of the physical features typical of AHO. Clinical overlap between PHP1a and PHP1b is thought to be caused by variable levels of Gsα activity expressed in specific cell types. GNAS encodes the Gsα protein, which is the α-subunit in the heterotrimeric G protein.
Maternally derived mutations are usually associated with PHPIa while PPHP are caused by paternally derived mutations. PHPIb is caused by deletions in one or several of the four differentially methylated regions (DMRs, see figure 1 in product description) of the GNAS locus or deletions in the STX16 gene.

The GNAS locus is a complex imprinted locus that generates multiple transcripts through the use of several alternative first exons that splice into a common set of downstream exons, see figure 1. The GNAS gene (13 exons) spans ~20 kb and is located on chromosome 20q13.32, 57.5 Mb from the p-telomere.
Due to differential methylation of their promoters, most gene products originate from one parental allele. Transcripts GNASXL, which encodes XLαs, GNAS1A (also referred to as A/B) and the antisense transcript NESPAS (also referred to as GNAS-AS1) are transcribed from the paternal allele, while NESP55 (also referred to as NESP) is transcribed from the maternal allele. The most downstream promoter (Gsα exon 1) is not differentially methylated, which results in GNAS expression from both alleles in most tissues.
The Gsα and XLαs transcripts are involved in downstream signaling from parathyroid hormone (PTH), parathyroid hormone related protein (PTHrP) receptors and other hormone receptors like TSHR and GHRHR. The GNAS1A transcript and the antisense transcript NESPAS are not translated into proteins, but are thought to influence Gsα expression via mechanisms that remain to be determined. The STX16 gene, lastly, is a long range control element of methylation at the GNAS locus, located more than 220 kb centromeric.

This SALSA® MS-MLPA® probemix is intended to provide information on deletions, duplications and aberrant methylation of sequences in the 20q13.32 GNAS region. Besides the detection of aberrant methylation, all 32 target probes present will give information on copy number changes in the analysed sample. The ME031-B1 GNAS probemix contains 25 probes specific for the GNAS locus, 6 for the STX16 gene, located ~220 kb centromeric and one for the TH1L (also referred to as NELFCD) gene, located 90 kb telomeric of GNAS. Of these, 17 are MS-MLPA probes containing a HhaI recognition site specific for the four differentially methylated regions of the GNAS locus. The probe targeting the TH1L gene also contains a HhaI recognition site.
In addition, 12 reference probes on different chromosomes and two MS-MLPA digestion control probes are included. The digestion control probes indicate whether or not restriction endonuclease digestion in the MS-MLPA reaction was complete.

This SALSA® MS-MLPA® probemix can be used to detect aberrant methylation of one or more sequences within the GNAS complex locus. Methylation levels can be different for different tissues. Please use DNA derived from the same type of tissue and purified by the same method as reference samples. This SALSA® MS-MLPA® probemix can also be used to detect deletions and duplications of one or more sequences in the GNAS region in a DNA sample. Heterozygous deletions of probe 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. Finally, note that most defects in genes are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.

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