PMC:1584416 / 32357-33966 JSONTXT

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Keeping in mind that the ~1,200 alleles known to exist for the CTRF gene implicated in the common autosomal recessive disorder cystic fibrosis alone [29] can theoretically result in ~700,000 different allelic combinations, the potential number of allelic combinations of different recessive mutations and single nucleotide polymorphisms genome-wide is currently incalculable. We suggest biallelic effects as a previously underestimated yet important variable in considering genotype–phenotype relationships from autosomal recessive disease to normal phenotypic diversity in mammals. Extension of the above concept implies that recessive mutations can enter evolutionary selection in F1 provided that the second allele carries a different recessive alteration. Finally, our data highlight the potential of clinically relevant alleles previously designated as null, with little or no detectable expression or activity, to nonetheless contribute to 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