2.%20protein%20polymorphisms%202011-1

2.%20protein%20polymorphisms%202011-1 - Molecular basis of...

Info iconThis preview shows pages 1–19. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Molecular basis of variation Variation in expressed genes: Qualitative Quantitative Methods and applications Variation at DNA level: Next lecture Strahan and Read, Chapter 13 Protein polymorphisms Variation in expressed protein sequences provided the frst evidence that genes acted directly to change biochemistry Sickle-cell anaemia Originally identifed in black populations in the Southern United States Characterized by sickle-cell crises in which patients had intense muscle pain, Fever and recurrent bouts oF anaemia Microscopic examination of blood smears Sickle cell Inheritance HbS discriminated by electrophoresis A single peptide difference in -chain Peptide sequencing led to identification of HbS mutation Hb A: val-his-leu-thr-pro-glu-glu-lys GAG Hb S: val-his-leu-thr-pro- val-glu-lys G U G First demonstration that a mutation resulted in a single amino acid substitution, which in turn was consistent with a single nucleotide change The hemoglobin S mutation Molecular basis for sickling Population distribution Molecular diagnosis of HbS Single AA substitions in Theory The extent of mutational variation is quite extreme Single amino acid substitutions From a theoretical viewpoint, given 3 possible substitutions at each base, there would be 9 variants of every codon 25% of these are synonomous, 2.5% are nonsense and 72.5% will result in AA substitutions (missense) For the hemoglobin genes, as of 1996, there were 587 known AA substitutions affecting 238 of the 287 AA Of the 9 possible changes in the normal alpha-gene chain termination codon, 4 are actually known Many are deleterious and occur only rarely, but common neutral variants may go undetected Variation in the hb molecule Variation in the hb molecule Variation in the hb molecule: genotype and phenotype Variation in the hb molecule: genotype and phenotype http://en.wikipedia.org/wiki/Hemoglobin Other types of protein variation Two amino acid substitutions in a single polypeptide: rare, and (almost) all involve second mutations on a common background Small deletions: 2-5 amino acids: rare Tandem repeats: eg., Hb Grady alpha: 115 116 117 118 116 117 118 119 Chain termination mutations: also rare Mutation of normal termination codon to a sense codon Loss of stop codon: Hb Constant Spring a chain mutation resulting in a peptide with 11 additional residues Frame shift: eg., Hb Wayne: only tolerated when near end of coding region Other types of protein variation Fusion sequences: known best in hemoglobin, haptoglobin, immune function proteins Mutation in untranslated regions: may be quite common, and may underline Mendelian variation in quantity of many specific proteins....
View Full Document

This note was uploaded on 10/12/2011 for the course BIOL 370 taught by Professor Levine during the Spring '11 term at McGill.

Page1 / 58

2.%20protein%20polymorphisms%202011-1 - Molecular basis of...

This preview shows document pages 1 - 19. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online