Estimating the Allele Frequency of Autosomal Recessive Disorders through Mutational Records and Consanguinity: The Homozygosity Index (HI)

Alessandro Gialluisi, Tommaso Pippucci, Yair Anikster, Ugur Ozbek, Myrna Medlej-Hashim, Andre Mégarbané, Giovanni Romeo

Research output: Contribution to journalArticlepeer-review

Abstract

In principle mutational records make it possible to estimate frequencies of disease alleles (q) for autosomal recessive disorders using a novel approach based on the calculation of the Homozygosity Index (HI), i.e., the proportion of homozygous patients, which is complementary to the proportion of compound heterozygous patients P(CH). In other words, the rarer the disorder, the higher will be the HI and the lower will be the P(CH). To test this hypothesis we used mutational records of individuals affected with Familial Mediterranean Fever (FMF) and Phenylketonuria (PKU), born to either consanguineous or apparently unrelated parents from six population samples of the Mediterranean region. Despite the unavailability of precise values of the inbreeding coefficient for the general population, which are needed in the case of apparently unrelated parents, our estimates of q are very similar to those of previous descriptive epidemiological studies. Finally, we inferred from simulation studies that the minimum sample size needed to use this approach is 25 patients either with unrelated or first cousin parents. These results show that the HI can be used to produce a ranking order of allele frequencies of autosomal recessive disorders, especially in populations with high rates of consanguineous marriages.

Original languageEnglish
Pages (from-to)159-167
Number of pages9
JournalAnnals of Human Genetics
Volume76
Issue number2
DOIs
StatePublished - Mar 2012
Externally publishedYes

Keywords

  • Autosomal recessive disorders
  • Disease allele frequency
  • Homozygosity index
  • Inbreeding

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