title: The evolutionary and clinical implications of the uneven distribution of the frequency of the inherited haemoglobin variants over short geographical distances.
abstract: Studies of the frequency of heterozygous carriers for common inherited diseases of haemoglobin in over 7500 adolescent children in 25 districts in Sri Lanka have disclosed a highly significant variation over very short geographical distances. A further analysis of these findings, including their relationship to the past frequency and distribution of malaria, climatic variation, altitude, ethnic origin and consanguinity rates, have provided evidence regarding the evolutionary basis for the variable distribution of these conditions over short distances. It is likely that the complex interplay between malaria and the environment, together with related ethnic and social issues, exists in many countries across the tropical belt. Hence, these observations emphasise the importance of micromapping heterozygote distributions in high-frequency countries in order to define their true burden and the facilities required for the prevention and management of the homozygous and compound heterozygous disorders that result from their interaction.
authors.affiliation: University of Kelaniya, Colombo, Sri Lanka.
authors.forename: Anuja
authors.initials: A
authors.lastname: Premawardhena
authors.affiliation: MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Allen
authors.affiliation: Imperial College, London, United Kingdom.
authors.forename: Fred
authors.initials: F
authors.lastname: Piel
authors.affiliation: MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Fisher
authors.affiliation: University of Kelaniya, Colombo, Sri Lanka.
authors.forename: Laxman
authors.initials: L
authors.lastname: Perera
authors.affiliation: University of Kelaniya, Colombo, Sri Lanka.
authors.forename: Rexan
authors.initials: R
authors.lastname: Rodrigo
authors.affiliation: University of Kelaniya, Colombo, Sri Lanka.
authors.forename: Gayan
authors.initials: G
authors.lastname: Goonathilaka
authors.affiliation: University of Kelaniya, Colombo, Sri Lanka.
authors.forename: Lebbe
authors.initials: L
authors.lastname: Ramees
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Peto
authors.affiliation: University of Toronto, Toronto, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.affiliation: MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Weatherall
mesh_terms: D000293:Adolescent; D000531:Altitude; D002980:Climate; D003241:Consanguinity; D005006:Ethnicity; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006453:Hemoglobinopathies / Q000453:epidemiology / Q000235:genetics; D006454:Hemoglobins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008288:Malaria; D008297:Male; D017720:Molecular Epidemiology; D013188:Sri Lanka / Q000453:epidemiology
chemical_list: D006454:Hemoglobins
keywords: consanguinity; distribution; haemoglobinopathies; malaria; micromapping