title: Consanguinity affects selection of alpha-thalassemia genotypes and the size of populations under selection pressure from malaria.
abstract: BACKGROUND
  In populations with alpha(+)-thalassemia gene deletion, the practice of consanguineous marriages is common.
  
  
  OBJECTIVE
  The study explored the impact of consanguinity (inbreeding) on the selection of alpha(+)-thalassemia genotypes in a computer model.
  
  
  METHODS
  In a population under selection pressure from malaria, a single protective mutation (-alpha/alphaalpha genotype) was introduced among normal genotypes (alphaalpha/alphaalpha), and mating allowed to proceed. Heterozygote (-alpha/alphaalpha) and homozygote (-alpha/-alpha) 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,-alpha/-alpha homozygotes reached a frequency of 0.5 faster than in less inbred populations. As the frequency of the alpha(+)-thalassemia allele in a population increases, however, the positive effect of inbreeding on the population growth decreases.
  
  
  CONCLUSIONS
  Under selection pressure from malaria, consanguinity may increase the speed of selection of-alpha/-alpha homozygotes and provide an advantage regarding population growth over non-consanguineous populations.
authors: Faculty of Medicine and Health Sciences, UAE University, Al Ain, Abu Dhabi, United Arab Emirates. s.denic@uaeu.ac.ae
authors: Srdjan
authors: S
authors: Denic
authors: Chris
authors: C
authors: Frampton
authors: Nicolas
authors: N
authors: Nagelkerke
authors: M Gary
authors: MG
authors: Nicholls
mesh_terms: D003198:Computer Simulation; D003241:Consanguinity; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008288:Malaria / Q000235:genetics*; D008957:Models, Genetic; D012641:Selection, Genetic; D017085:alpha-Thalassemia / Q000209:etiology / Q000235:genetics*