Loss of information due to ambiguous haplotyping of SNPs (original) (raw)

To quantify the extent of haplotype (phase) ambiguity, we assume k diallelic loci, Hardy-Weinberg equilibrium and linkage equilibrium. We denote the alleles at the ith locus as Ai and Bi, with frequencies pi and qi=1-pi, respectively. The total number of possible genotypes (ignoring linkage phase) is 3k, because there are three possibilities (AiAi, AiBi, BiBi) at each locus.

An 'ambiguous individual' is one whose haplotypes cannot be inferred with certainty. For example, an A1B1,B2B2,A3B3 individual may be haplotyped as A1B2A3/B1B2B3 or A1B2B3/B1B2A3, and is thus ambiguous. An individual is ambiguous if, and only if, s/he is heterozygous at two or more loci. The number of ambiguous k-locus genotypes is found by subtracting from 3k the number of genotypes homozygous at all k loci (2_k_) or at exactly k-1 loci (_k_2_k_-1), yielding 3_k_-2_k_-_k_2_k_-1 (for example, for k=3, there are 7 ambiguous genotypes: A1B1,A2B2,A3A3; A1B1,A2B2,B3B3; A1B1,A2A2,A3B3; A1B1,B2B2,A3B3; A1A1,A2B2,A3B3; B1B1,A2B2,A3B3; A1B1,A2B2,A3B3).

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Acknowledgements

We thank H. Göring, J. Hoh, F. Collins and K. Weiss for helpful comments. This work was supported in part by grants MH-48858, DK-31813, DK-31775, HG-00376 and HL-35018.

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Authors and Affiliations

  1. Department of Psychiatry, Columbia University, NY State Psychiatric Institute, Unit 24, 1051 Riverside Drive, New York, 10032, New York, USA
    Susan E. Hodge
  2. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, 48109, Michigan, USA
    Michael Boehnke
  3. Department of Pediatrics, UC Irvine Medical Center, Orange, 92868, California, USA
    M. Anne Spence

Authors

  1. Susan E. Hodge
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  2. Michael Boehnke
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  3. M. Anne Spence
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Correspondence toSusan E. Hodge.

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Hodge, S., Boehnke, M. & Spence, M. Loss of information due to ambiguous haplotyping of SNPs.Nat Genet 21, 360–361 (1999). https://doi.org/10.1038/7687

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