Persistence of the Common Hartnup disease D173N Allele in populations of European origin
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Azmanov, Dimitar; Rodgers, Helen; Auray-Blais, Christiane; Giguere, Robert; Bailey, Charles; Broer, Stefan; Rasko, John Edward; Cavanaugh, Juleen
Description
Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from apparently unrelated families from both Australia and North America. We report an investigation of the origins of the D173N allele using a unique combination of variants including...[Show more]
dc.contributor.author | Azmanov, Dimitar | |
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dc.contributor.author | Rodgers, Helen | |
dc.contributor.author | Auray-Blais, Christiane | |
dc.contributor.author | Giguere, Robert | |
dc.contributor.author | Bailey, Charles | |
dc.contributor.author | Broer, Stefan | |
dc.contributor.author | Rasko, John Edward | |
dc.contributor.author | Cavanaugh, Juleen | |
dc.date.accessioned | 2015-12-08T22:16:44Z | |
dc.identifier.issn | 0003-4800 | |
dc.identifier.uri | http://hdl.handle.net/1885/30809 | |
dc.description.abstract | Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from apparently unrelated families from both Australia and North America. We report an investigation of the origins of the D173N allele using a unique combination of variants including SNPs, microsatellites, and a VNTR across 211 Kb spanning the SLC6A19 locus. All individuals who carry the mutant allele share an identical core haplotype suggesting a single common ancestor, indicating that the elevated frequency of the D173 N allele is not a result of recurrent mutation. Analyses of these data indicate that the allele is more than 1000 years old. We compare the reasons for survival of this allele with other major alleles in some other common autosomal recessive diseases occurring in European Caucasians. We postulate that survival of this allele may be a consequence of failure of the allele to completely inactivate the transport of neutral amino acids. | |
dc.publisher | Cambridge University Press | |
dc.source | Annals of Human Genetics | |
dc.subject | Keywords: amino acid; carrier protein; protein slc6a19; unclassified drug; amino acid substitution; amino acid transport; article; autosomal recessive disorder; Caucasian; controlled study; Europe; gene frequency; gene function; gene locus; genetic association; gen Aminoaciduria; D173N; Evolution; Hartnup; SLC6A19 | |
dc.title | Persistence of the Common Hartnup disease D173N Allele in populations of European origin | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 71 | |
dc.date.issued | 2007 | |
local.identifier.absfor | 060411 - Population, Ecological and Evolutionary Genetics | |
local.identifier.absfor | 060499 - Genetics not elsewhere classified | |
local.identifier.absfor | 110311 - Medical Genetics (excl. Cancer Genetics) | |
local.identifier.ariespublication | u4325460xPUB77 | |
local.type.status | Published Version | |
local.contributor.affiliation | Azmanov, Dimitar, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Rodgers, Helen, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Auray-Blais, Christiane, Universite de Sherbrooke | |
local.contributor.affiliation | Giguere, Robert, Universite de Sherbrooke | |
local.contributor.affiliation | Bailey, Charles, Centenary Institute of Cancer Medicine and Cell Biology | |
local.contributor.affiliation | Broer, Stefan, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Rasko, John Edward, University of Sydney | |
local.contributor.affiliation | Cavanaugh, Juleen, College of Medicine, Biology and Environment, ANU | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.startpage | 1 | |
local.bibliographicCitation.lastpage | 11 | |
local.identifier.doi | 10.1111/j.1469-1809.2007.00375.x | |
dc.date.updated | 2015-12-08T08:04:03Z | |
local.identifier.scopusID | 2-s2.0-34948819167 | |
Collections | ANU Research Publications |
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