title: Estimating the Total Pathogenic Allele Frequency of Autosomal Recessive Disorders in Case of Consanguinity.
abstract: OBJECTIVE
  Estimating the total allele frequency of all pathogenic alleles of an autosomal recessive disease is not possible if only mutational data of a sample of affected individuals are available. However, if the affected individuals come from a population where consanguinity is not uncommon, this total allele frequency can be estimated by additionally using the positive individual inbreeding coefficients or an estimate of the population inbreeding coefficient. In this paper, we propose two estimators.
  
  
  RESULTS
  We propose to estimate the total allele frequency by a conditional maximum likelihood estimator if a part of the affected individuals in the sample comes from consanguineous marriages with known inbreeding coefficients. A simulation study shows that this estimator is unbiased and robust. We propose a second estimator which is based on an estimate of the population inbreeding coefficient. The method is applied to mutational data and individual inbreeding coefficients of Tunisian patients with congenital adrenal hyperplasia.
  
  
  CONCLUSIONS
  Additionally using individual inbreeding coefficients or an estimate of the population inbreeding coefficient makes it possible to estimate the total allele frequency. Since consanguinity is commonly practiced in many parts of the world, the estimators proposed in the paper are of practical importance.
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marianne A
authors.initials: MA
authors.lastname: Jonker
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Teeuw
authors.forename: Wided
authors.initials: W
authors.lastname: Kelmemi
authors.forename: Maher
authors.initials: M
authors.lastname: Kharrat
authors.forename: Habiba
authors.initials: H
authors.lastname: Chaabouni-Bouhamed
authors.forename: Leo P
authors.initials: LP
authors.lastname: Ten Kate
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics; D000483:Alleles; D003241:Consanguinity; D005787:Gene Frequency; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D009154:Mutation; D014416:Tunisia