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Paternally inherited HLA alleles are associated with women's choice of male odor

Abstract

The major histocompatibility complex (MHC) is a source of unique individual odors that influence individual recognition, mating preferences, nesting behavior and selective block of pregnancy in animals1,2,3,4,5,6,7,8,9,10. Such phenomena have been difficult to study in humans, because the human leukocyte antigen (HLA, human MHC) loci are the most polymorphic loci in the human genome11, with the potential to generate millions of unique combinations of genotypes. In addition, high variability in background odors, encoded by the rest of the genome and influenced by cultural practices, contribute to a low signal-to-noise ratio that could mask HLA-based olfactory cues. Here we show that women can detect differences of one HLA allele among male odor donors with different MHC genotypes. Notably, the mechanism for a woman's ability to discriminate and choose odors is based on HLA alleles inherited from her father but not her mother. The parents' HLA alleles that she does not inherit show no relationship with odor choice, despite exposure to these HLA-encoded odors throughout her life. Our data indicate that paternally inherited HLA-associated odors influence odor preference and may serve as social cues.

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Figure 1: Number of allele matches between each smeller/donor pair.
Figure 2: Number of matching HLA alleles and odor choice.
Figure 3: Effects of inheritance and parental origin of HLA alleles on odor choice.

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Acknowledgements

We thank D. Hayreh and P. Klimczyk for assistance on field trips, K. Beaman for serological HLA typing the donors in this study, C. Wedekind for sharing unpublished protocols and J. Brown for helpful comments. This work was supported by a MERIT Award from the National Institute of Mental Health, a grant from the John T. and Catherine D. MacArthur Foundation (to M.K.M.), a grant from the National Institute of Child Health and Development (to C.O.) and an MD/PhD Training Grant from the National Institutes of Health (to S.J.).

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Correspondence to Martha K. McClintock.

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Jacob, S., McClintock, M., Zelano, B. et al. Paternally inherited HLA alleles are associated with women's choice of male odor. Nat Genet 30, 175–179 (2002). https://doi.org/10.1038/ng830

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