The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

Hdl Handle:
http://hdl.handle.net/10147/263373
Title:
The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.
Authors:
Flanagan, J M; McMahon, G; Brendan Chia, S H; Fitzpatrick, P; Tighe, O; O'Neill, C; Briones, P; Gort, L; Kozak, L; Magee, A; Naughten, E; Radomyska, B; Schwartz, M; Shin, J S; Strobl, W M; Tyfield, L A; Waterham, H R; Russell, H; Bertorelle, G; Reichardt, J K V; Mayne, P D; Croke, D T
Affiliation:
Department of Pathology, The Children's University Hospital, Dublin, Ireland. Jonathan.Flanagan@stjude.org
Citation:
The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations. 2010, 104 (2):148-54 Heredity (Edinb)
Journal:
Heredity
Issue Date:
Feb-2010
URI:
http://hdl.handle.net/10147/263373
DOI:
10.1038/hdy.2009.84
PubMed ID:
19639008
Abstract:
Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.
Item Type:
Article
Language:
en
MeSH:
Europe; European Continental Ancestry Group; Female; Galactosemias; Gene Frequency; Humans; Male; Mutation, Missense; Polymorphism, Single Nucleotide; UDPglucose-Hexose-1-Phosphate Uridylyltransferase
ISSN:
1365-2540

Full metadata record

DC FieldValue Language
dc.contributor.authorFlanagan, J Men_GB
dc.contributor.authorMcMahon, Gen_GB
dc.contributor.authorBrendan Chia, S Hen_GB
dc.contributor.authorFitzpatrick, Pen_GB
dc.contributor.authorTighe, Oen_GB
dc.contributor.authorO'Neill, Cen_GB
dc.contributor.authorBriones, Pen_GB
dc.contributor.authorGort, Len_GB
dc.contributor.authorKozak, Len_GB
dc.contributor.authorMagee, Aen_GB
dc.contributor.authorNaughten, Een_GB
dc.contributor.authorRadomyska, Ben_GB
dc.contributor.authorSchwartz, Men_GB
dc.contributor.authorShin, J Sen_GB
dc.contributor.authorStrobl, W Men_GB
dc.contributor.authorTyfield, L Aen_GB
dc.contributor.authorWaterham, H Ren_GB
dc.contributor.authorRussell, Hen_GB
dc.contributor.authorBertorelle, Gen_GB
dc.contributor.authorReichardt, J K Ven_GB
dc.contributor.authorMayne, P Den_GB
dc.contributor.authorCroke, D Ten_GB
dc.date.accessioned2012-12-20T11:38:46Z-
dc.date.available2012-12-20T11:38:46Z-
dc.date.issued2010-02-
dc.identifier.citationThe role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations. 2010, 104 (2):148-54 Heredity (Edinb)en_GB
dc.identifier.issn1365-2540-
dc.identifier.pmid19639008-
dc.identifier.doi10.1038/hdy.2009.84-
dc.identifier.urihttp://hdl.handle.net/10147/263373-
dc.description.abstractClassical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Heredityen_GB
dc.subject.meshEurope-
dc.subject.meshEuropean Continental Ancestry Group-
dc.subject.meshFemale-
dc.subject.meshGalactosemias-
dc.subject.meshGene Frequency-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMutation, Missense-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshUDPglucose-Hexose-1-Phosphate Uridylyltransferase-
dc.titleThe role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, The Children's University Hospital, Dublin, Ireland. Jonathan.Flanagan@stjude.orgen_GB
dc.identifier.journalHeredityen_GB
dc.description.provinceLeinsteren

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