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
Hb-Mainz Physical Effects According to the variant database, Hb-Mainz causes hemoglobin to become unstable and also causes hemolytic severe anemia.
Hb M-Saskatoon Mutation
M-Saskatoon Detailed Sequence (Mutated) Nucleotide Sequence (444 nt): ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAAC GTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAG AGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGT GAAGGCTTATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAA CCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCT GAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAA GAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCC TGGCCCACAAGTATCACTAA (Mutated) Translation (147 aa): MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKV KAYGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTP PVQAAYQKVVAGVANALAHKYH CAT becomes TAT H becomes Y
Amino Acid Change HistidineTyrosine →
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 bin/hbvar/query_vars3?mode=output&display_f ormat=page&i=387 bin/hbvar/query_vars3?mode=output&display_f ormat=page&i=387 /beta/Shepherds.Bush.html /beta/Shepherds.Bush.html wC&lpg=RA1- PA1623&ots=A9ufCRxiMW&dq=Shepherds%20Bu sh%20mutat&pg=RA1- PA1623#v=onepage&q=shepherds%20bush&f=fal se wC&lpg=RA1- PA1623&ots=A9ufCRxiMW&dq=Shepherds%20Bu sh%20mutat&pg=RA1- PA1623#v=onepage&q=shepherds%20bush&f=fal se
Sources for Hb-Mainz bin/hbvar/query_vars3?mode=output&displa y_format=page&i=451 bin/hbvar/query_vars3?mode=output&displa y_format=page&i=