PROTEIN AND DNA-SEQUENCE ANALYSIS OF A PRIVATE GENETIC VARIANT - ALBUMIN-ORTONOVO (GLU-505-]LYS)

Citation
M. Galliano et al., PROTEIN AND DNA-SEQUENCE ANALYSIS OF A PRIVATE GENETIC VARIANT - ALBUMIN-ORTONOVO (GLU-505-]LYS), Biochimica et biophysica acta, 1225(1), 1993, pp. 27-32
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biophysics,Biology
ISSN journal
0006-3002
Volume
1225
Issue
1
Year of publication
1993
Pages
27 - 32
Database
ISI
SICI code
0006-3002(1993)1225:1<27:PADAOA>2.0.ZU;2-#
Abstract
Albumin Ortonovo is a slow moving variant of human serum albumin which has been found only in people coming from the small villages of Orton ovo and Nicola (Liguria, Italy) and reaches polymorphic frequency (gre ater than or equal to 1%) in the poorly admired population group livin g in that area. This is the first report of a 'private' variant detect ed in a Caucasian population. It probably originated as a mutation in a founder individual many generations ago. Isoelectric focusing analys is of CNBr fragments from the purified variant localized the mutation in fragment CNBr VI (residues 447-548). This fragment was isolated on a preparative scale by reversed-phase HPLC and subjected to Vs protein ase digestion. Sequence analysis of the abnormal Vs peptide revealed t hat the variant arises from a previously unreported substitution at po sition 505 where glutamic acid has been replaced by lysine. The protei n data were confirmed by DNA sequence analysis which indicated a singl e nucleotide change of GAA --> AAA in the corresponding codon of the s tructural gene. Since the amino acid substitution found in albumin Ort onovo accords with its electrophoretic mobility on cellulose acetate, residue 505 is probably exposed to the solvent. The clustering of the mutations in the intersubdomain connection linking subdomains IIIA and IIIB (residues 492-511) accords with the fact that this region lies o n the molecular surface and is accessible to solvent.