title: A human homolog of bacterial acetolactate synthase genes maps within the CADASIL critical region.
abstract: CADASIL, a recently identified autosomal dominant condition characterized by the recurrence of subcortical infarcts leading to dementia, was previously mapped to chromosome 19p13.1 within a 2-cM interval, D19S226-D19S199. No recombination event was observed with D19S841, a highly polymorphic microsatellite marker isolated from a cosmid mapped to this region. We recently identified within this cosmid a conserved sequence that we used to screen a fetal brain cDNA library and isolated an ubiquitous and abundantly transcribed gene. We did not detect any mutation of this gene in CADASIL patients, suggesting that it is not implicated in this disorder. Interestingly, this gene encodes a putative protein homologous to several thiamine pyrophosphate-binding proteins previously identified in bacteria, yeast, and plants. The proteins with the highest degree of similarity were the acetolactate synthase enzymes which, in prokaryotes, are involved in the branched chain amino acid biosynthetic pathway, raising fascinating questions on the yet unknown function of this gene in mammals.
authors.affiliation: INSERM U25, Paris, France. joutel@necker.fr
authors.forename: A
authors.initials: A
authors.lastname: Joutel
authors.forename: A
authors.initials: A
authors.lastname: Ducros
authors.forename: S
authors.initials: S
authors.lastname: Alamowitch
authors.forename: C
authors.initials: C
authors.lastname: Cruaud
authors.forename: V
authors.initials: V
authors.lastname: Domenga
authors.forename: E
authors.initials: E
authors.lastname: Maréchal
authors.forename: K
authors.initials: K
authors.lastname: Vahedi
authors.forename: H
authors.initials: H
authors.lastname: Chabriat
authors.forename: M G
authors.initials: MG
authors.lastname: Bousser
authors.forename: E
authors.initials: E
authors.lastname: Tournier-Lasserve
mesh_terms: D000095:Acetolactate Synthase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002539:Cerebral Arterial Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D018076:DNA, Complementary; D015161:Dementia, Multi-Infarct / Q000235:genetics*; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D018076:DNA, Complementary; D000095:Acetolactate Synthase