Group three - Notch 1 (Heather, Sana, Sebastian)
---+ Introduction

*Notch signalling is a very important signalling pathway in both development and disease. First identified in drosophila, notch signalling is most commonly associated with the process of lateral inhibition. Upon cell contact notch ligands (Jag1,2,Dll1,3,4) bind notch receptors (Notch1,2,3,4), activating a cleavage event by the ADAM protease which sheds the Notch receptor extracellular domain revealing an underlying gamma secretase cleavage site. Upon gamma secretase cleavage the intracellular portion of the notch receptor is released and translocates to the nucleus where it binds the DNA binding protein CSL. Classically this interaction leads to transcriptional activation of the target genes Hes and Hey.*



*- taken from Cell Signalling*

*Predicted functional partners and crystal structure of the mouse Notch1 Receptor - SMART (String)*



*General information about Notch1, such as the locus on the genome, splice variants and conserved regions in different species are found in the UCSC-genome browser. Information on the domain-structure of Notch1 and correlated functions of individual domains is found at the Pfam-database. Information about these topics is found at SebastiansAnalysis*

*Notch1 ReceptorExpression in early embryonic development, discrepancies in databases....*

*Notch regulation and target gene regulation through aligned/conserved TranscriptionFactorBindingSites*

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---+ Multiple Sequence Alignment

*Representation of a gene Multiple Sequence Alignment produced with ClustalW for Genomic sequences of Notch 1 and sequences from other 4 different species. The sequences were obtained in FASTA format from the UCSC -Genome Browser searching with the gene name. The asterisk at the Alignment represent the nucleotide conservation:* MultipleSequencealignment *

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---+ SNP information

*Important knowledge about Notch1-SNPs related to diseases are explained here SNP1.PNG*

*When I selected the rs 10521 green (Green: Coding-Synonomous) I got this conflicting result from the collection of functional SNPs that specifically prioritized for disease association studies then I found: *F-SNP.PNG*

*when I selected the red rs 41309766 (Red: Coding-Non synonomous) I got this result: F-SNP2.PNG*

*Then after, when I compared this rs 10521 green in another different SNP database (dbNSP) , I found the Clinical association with it is : Unknown*

* dbSNP*

*http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?searchType=adhoc_search&type=rs&rs=rs10521*

*I done the same with the red rs 41309766 in dbNSP, the clinical association with this SNP is also I found it unkown:*

*http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?searchType=adhoc_search&type=rs&rs=rs41309766*

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---+ References

*http://www.cellsignal.com/pathways/wnt-hedgehog.jsp*

*http://smart.embl.de/smart/show_motifs.pl?ID=CG3936-PA&GENOMIC=1*

*http://compbio.cs.queensu.ca/F-SNP/*

*http://www.ncbi.nlm.nih.gov/projects/SNP/*

*http://genome.uscs.edu/*