Detection and assignment of mutations and minihaplotypes in human DNA using peptide mass signature genotyping (PMSG): application to the human RDS/peripherin gene.
Peptide mass-signature genotyping (PMSG) is a scanning genotyping method that identifies mutations and polymorphisms by translating the sequence of interest in more than one reading frame and measuring the masses of the resulting peptides by mass spectrometry. PMSG was applied to the RDS/peripherin gene of 16 individuals from a family exhibiting autosomal dominant macular degeneration. The method revealed an A-->T transversion in the 5' splice site of intron 2 that is the likely cause of the disease. It also revealed four different minihaplotypes in exon 3 that represent particular combinations of SNPs at four different locations. This study demonstrates the utility of PMSG for identifying and characterizing point mutations and local minihaplotypes that are not readily analyzed by other approaches.
Telmer
Cheryl A
CA
SpectraGenetics LLC, Pittsburgh, Pennsylvania 15213, USA. cheryl.telmer@spectragenetics.com
Retchless
Adam C
AC
Kinsey
Ashley D
AD
Conley
Yvette
Y
Rigatti
Brian
B
Gorin
Michael B
MB
Jarvik
Jonathan W
JW
Retchless
Adam R
AR
D004252:DNA Mutational Analysis / Q000379:methods; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010455:Peptides / Q000737:chemistry / Q000235:genetics*; D064531:Peripherins; D012162:Retinal Degeneration / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D010455:Peptides; D064531:Peripherins