Shepherds Bush Physical Signs According to the variant database, this mutation manifests itself as an increase in oxygen affinity. It also results in a decreased bpg (2,3-dpg). Moreover, the mutation causes the hemoglobin to be unstable and hemolytic anemia
3D Protein Sequence of Hemoglobin Histidine is a positively charged hydrophilic amino acid Tyrosine is an uncharged hydrophilic amino acid What do you notice about where this mutation is near to? We will come back to this…
M-Saskatoon, Methemoglobinemia Special class of low O 2 affinity hemoglobin variant Iron in the heme is in an abnormal oxidation state Known as methemoglobin. – useless in O 2 binding. Has a brown pigment Causes cyanosis Mutation may also cause Dissociation of Dimers
Thalassemias Mutation of Initiation Codon ATG -> ATA beta0 (Original) Nucleotide Sequence (444 nt): ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTT GGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGAT CTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTA GTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCT GCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAA GAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGT ATCACTAA (Original) Translation (147 aa): MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFS DGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH RED – Initiation Codon that changes to ATA which no longer begins the reading frame Blue- Region of nucleotide base pairings, amino acids, and protein that is not read because of the mutation to the START codon Orange- Codon which becomes the START codon but originally is split into two codons before the mutation. All subsequent amino acids change in the translation Green- New Stop Codon
Protein Structure and Description of Effects of Mutation Aspartic Acid is hydrophilic and negatively charged polar Valine is hydrophobic and non polar making it mildly unstable The change in the protein sequence may affect Hb function in cells as it causes an alteration in the protein shape
Effects of Hb Rocky Mountain Those with an Hb Rocky Mountain mutation (a.k.a. Hb Paddington) develop Microcytosis Smaller red blood cells Those with mutation are at higher risk of being anemic Why do you think that is if the red blood cell count is the same as a healthy person?
Useful Sites for Sheperds Bush/ Biblography http://globin.bx.psu.edu/cgi- bin/hbvar/query_vars3?mode=output&display_f ormat=page&i=387 http://globin.bx.psu.edu/cgi- bin/hbvar/query_vars3?mode=output&display_f ormat=page&i=387 http://globin.cse.psu.edu/html/huisman/variants /beta/Shepherds.Bush.html http://globin.cse.psu.edu/html/huisman/variants /beta/Shepherds.Bush.html http://books.google.com/books?id=H85dwxYTKL wC&lpg=RA1- PA1623&ots=A9ufCRxiMW&dq=Shepherds%20Bu sh%20mutat&pg=RA1- PA1623#v=onepage&q=shepherds%20bush&f=fal se http://books.google.com/books?id=H85dwxYTKL wC&lpg=RA1- PA1623&ots=A9ufCRxiMW&dq=Shepherds%20Bu sh%20mutat&pg=RA1- PA1623#v=onepage&q=shepherds%20bush&f=fal se