TY - JOUR
T1 - Consanguinity affects selection of alpha-thalassemia genotypes and the size of populations under selection pressure from malaria
AU - Denic, Srdjan
AU - Frampton, Chris
AU - Nagelkerke, Nicolas
AU - Nicholls, M. Gary
N1 - Funding Information:
This study was supported by the Sheikh Hamdan bin Rashid Al Maktoum Award for Medical Sciences (5/2003-2004).
PY - 2007/11
Y1 - 2007/11
N2 - Background: In populations with α+-thalassemia gene deletion, the practice of consanguineous marriages is common. Aim: The study explored the impact of consanguinity (inbreeding) on the selection of α+-thalassemia genotypes in a computer model. Method: In a population under selection pressure from malaria, a single protective mutation (-α/αα genotype) was introduced among normal genotypes (αα/αα), and mating allowed to proceed. Heterozygote (-α/αα) and homozygote (-α/-α) children were 1.5 and 2.5 times more likely to survive malaria than those with normal genotypes. Using different coefficients of inbreeding (F, range 0-0.12), we examined the effect of population size, and the mean number of generations required for the homozygote frequency to reach 0.5. Results: On average, consanguineous populations were larger than randomly mating populations and the size was directly proportional to F. In more inbred populations,-α/-α homozygotes reached a frequency of 0.5 faster than in less inbred populations. As the frequency of the α+-thalassemia allele in a population increases, however, the positive effect of inbreeding on the population growth decreases. Conclusion: Under selection pressure from malaria, consanguinity may increase the speed of selection of-α/-α homozygotes and provide an advantage regarding population growth over non-consanguineous populations.
AB - Background: In populations with α+-thalassemia gene deletion, the practice of consanguineous marriages is common. Aim: The study explored the impact of consanguinity (inbreeding) on the selection of α+-thalassemia genotypes in a computer model. Method: In a population under selection pressure from malaria, a single protective mutation (-α/αα genotype) was introduced among normal genotypes (αα/αα), and mating allowed to proceed. Heterozygote (-α/αα) and homozygote (-α/-α) children were 1.5 and 2.5 times more likely to survive malaria than those with normal genotypes. Using different coefficients of inbreeding (F, range 0-0.12), we examined the effect of population size, and the mean number of generations required for the homozygote frequency to reach 0.5. Results: On average, consanguineous populations were larger than randomly mating populations and the size was directly proportional to F. In more inbred populations,-α/-α homozygotes reached a frequency of 0.5 faster than in less inbred populations. As the frequency of the α+-thalassemia allele in a population increases, however, the positive effect of inbreeding on the population growth decreases. Conclusion: Under selection pressure from malaria, consanguinity may increase the speed of selection of-α/-α homozygotes and provide an advantage regarding population growth over non-consanguineous populations.
KW - Alpha-thalassemia
KW - Computer modeling
KW - Consanguinity
KW - Inbreeding
KW - Malaria
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U2 - 10.1080/03014460701615993
DO - 10.1080/03014460701615993
M3 - Article
C2 - 18092206
AN - SCOPUS:40949124880
SN - 0301-4460
VL - 34
SP - 620
EP - 631
JO - Annals of Human Biology
JF - Annals of Human Biology
IS - 6
ER -