TY - JOUR
T1 - The STR252 - IVS10nt546 - VNTR7 phenylalanine hydroxylase minihaplotype in five mediterranean samples
AU - Calì, Francesco
AU - Dianzani, Irma
AU - Desviat, Lourdes R.
AU - Perez, Belen
AU - Ugarte, Magdalena
AU - Ozguc, Meral
AU - Seyrantepe, Volkan
AU - Shiloh, Yossi
AU - Giannattasio, Sergio
AU - Carducci, Carla
AU - Bosco, Paolo
AU - De Leo, Giacomo
AU - Piazza, Alberto
AU - Romano, Valentino
N1 - Funding Information:
Acknowledgements We wish to thank Turgay Coskun and Im-ram Ozalp (Hacettepe Pediatrics Unit of Metabolism, Ankara) for valuable suggestions. This study was partially funded by Progetto di Ricerca Corrente, the Italian Ministry of Health, contract number ICS-190.1/TC/95.58; Progetto Finalizzato C.N.R., “Beni Cul-turali”; European Commission TMR, contract number ER-BCHRXCT92003; and CNR Target Project FATMA. We thank Alda Ragalmuto for preparing typescripts.
PY - 1997
Y1 - 1997
N2 - IVS10nt546 (IVS10nt-llg→a) is the most common molecular defect of the phenylalanine hydroxylase gene causing phenylketonuria in Mediterranean populations. Previous studies have proposed various and alternative hypotheses concerning the geographical origin and pattern of diffusion of this mutation in this area. In this study, this issue was re-examined on a large sample (149) of 'Mediterranean' IVS10nt546 mutant alleles analysed with multiallelic intragenic polymorphisms. The analysis of intragenic microsatellite (STR) and minisatellite (VNTR) polymorphisms shows allelic heterogeneity of the IVS10nt546 mutation. Eight STR and three VNTR alleles were found in association with the splicing defect. Of the ten detected STR-VNTR combinations ('minihaplotypes'), we identified a predominant allelic association (VNTR7 - STR252) embedded in a RFLP-haplotype 6 background, which seems to correspond to the ancestral gene originating in the Turkey-Israel area. Analysis of both absolute and relative gene frequencies of the STR252 IVS10nt546 - VNTR7 minihaplotypes, shows statistically significant (P < 0.02) variations and may suggest gene flow from Turkey and/or Israel to Italy and Spain. The associated migratory events need not be unique in time (and people) but seem to suggest they may be traced back to the expansion of the Neolithic culture and people, thus allowing dating of the origin of this mutation to at least 5000-10,000 years ago. Alternative hypotheses are discussed to explain, in light of the available historical and pre-historical evidence, the pattern of diffusion of the IVS10nt546 mutation in the Mediterranean basin.
AB - IVS10nt546 (IVS10nt-llg→a) is the most common molecular defect of the phenylalanine hydroxylase gene causing phenylketonuria in Mediterranean populations. Previous studies have proposed various and alternative hypotheses concerning the geographical origin and pattern of diffusion of this mutation in this area. In this study, this issue was re-examined on a large sample (149) of 'Mediterranean' IVS10nt546 mutant alleles analysed with multiallelic intragenic polymorphisms. The analysis of intragenic microsatellite (STR) and minisatellite (VNTR) polymorphisms shows allelic heterogeneity of the IVS10nt546 mutation. Eight STR and three VNTR alleles were found in association with the splicing defect. Of the ten detected STR-VNTR combinations ('minihaplotypes'), we identified a predominant allelic association (VNTR7 - STR252) embedded in a RFLP-haplotype 6 background, which seems to correspond to the ancestral gene originating in the Turkey-Israel area. Analysis of both absolute and relative gene frequencies of the STR252 IVS10nt546 - VNTR7 minihaplotypes, shows statistically significant (P < 0.02) variations and may suggest gene flow from Turkey and/or Israel to Italy and Spain. The associated migratory events need not be unique in time (and people) but seem to suggest they may be traced back to the expansion of the Neolithic culture and people, thus allowing dating of the origin of this mutation to at least 5000-10,000 years ago. Alternative hypotheses are discussed to explain, in light of the available historical and pre-historical evidence, the pattern of diffusion of the IVS10nt546 mutation in the Mediterranean basin.
UR - http://www.scopus.com/inward/record.url?scp=0030922785&partnerID=8YFLogxK
U2 - 10.1007/s004390050515
DO - 10.1007/s004390050515
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AN - SCOPUS:0030922785
SN - 0340-6717
VL - 100
SP - 350
EP - 355
JO - Human Genetics
JF - Human Genetics
IS - 3-4
ER -