Bibliographie : HLA et Odeurs Corporelles

Kristin G. Ardlie, Leonid Kruglyak and Mark Seielstad : Nature Reviews Genetics 3, 299–309 (2002) + correction

Patterns of Linkage Disequilibrium in the Human Genome

ABSTRACT : Particular alleles at neighbouring loci tend to be co-inherited. For tightly linked loci, this might lead to associations between alleles in the population — a property known as linkage disequilibrium (LD). LD has recently become the focus of intense study in the hope that it might facilitate the mapping of complex disease loci through whole-genome association studies. This approach depends crucially on the patterns of LD in the human genome. In this review, we draw on empirical studies in humans and Drosophila, as well as simulation studies, to assess the current state of knowledge about patterns of LD, and consider the implications for the use of LD as a mapping tool.

A. Arnaiz-Villena, K. Dimitroski, A. Pacho, J. Moscoso, E. Gomez-Casado, C. Silvera-Redondo, P. Varela, M. Blagoevska, V. Zdravkovska, J. Martınez-Laso : Tissue Antigens 2001: 57: 118–127

HLA genes in Macedonians and the sub-Saharan origin of the Greeks

ABSTRACT : HLA alleles have been determined in individuals from the Republic of Macedonia by DNA typing and sequencing. HLA-A, -B, -DR, -DQ allele frequencies and extended haplotypes have been for the first time determined and the results compared to those of other Mediterraneans, particularly with their neighbouring Greeks. Genetic distances, neighbor-joining dendrograms and correspondence analysis have been performed. The following conclusions have been reached: 1) Macedonians belong to the ‘‘older’’ Mediterranean substratum, like Iberians (including Basques), North Africans, Italians, French, Cretans, Jews, Lebanese, Turks (Anatolians), Armenians and Iranians, 2) Macedonians are not related with geographically close Greeks, who do not belong to the ‘‘older’’ Mediterranenan substratum, 3) Greeks are found to have a substantial relatedness to sub-Saharan (Ethiopian) people, which separate them from other Mediterranean groups. Both Greeks and Ethiopians share quasi-specific DRB1 alleles, such as *0305, *0307, *0411, *0413, *0416, *0417, *0420, *1110, *1112, *1304 and *1310. Genetic distances are closer between Greeks and Ethiopian/sub-Saharan groups than to any other Mediterranean group and finally Greeks cluster with Ethiopians/sub-Saharans in both neighbour joining dendrograms and correspondence analyses. The time period when these relationships might have occurred was ancient but uncertain and might be related to the displacement of Egyptian-Ethiopian people living in pharaonic Egypt.

Thomas Boehm and Frank Zufall : Trends in Neurosciences, Vol.29 No.2, February 2006, pp. 100-107

MHC peptides and the sensory evaluation of genotype

ABSTRACT : Social interactions, such as finding and identifying a mate, often rely on the ability to sense molecular cues carrying information about genetic relationship and individuality. We summarize recent evidence for an unexpected mechanistic link between the immune and olfactory systems in enabling this identification process. In addition to their established role in the immune response, peptide ligands of major histocompatibility complex (MHC) molecules constitute a previously unknown family of social recognition signals detected by specific subsets of sensory neurons in the mammalian nose. This sensing of MHC peptides can be viewed as a form of functional genome analysis by the nose. Behavioral studies in mice and fish show that MHC peptides are accepted as olfactory cues that influence mate choice decisions and selective pregnancy failure. These findings provide a molecular mechanism by which an individual can sense the composition and compatibility of vital immune system molecules of a conspecific, with direct consequences for social behavior.

Anke Ehlers, Stephan Beck, Simon A. Forbes, John Trowsdale, Armin Volz, Ruth Younger and Andreas Ziegler : Genome Res. 2000 10: 1968-1978

MHC-Linked Olfactory Receptor Loci Exhibit Polymorphism and Contribute to Extended HLA/OR-Haplotypes

ABSTRACT : Clusters of olfactory receptor (OR) genes are found on most human chromosomes. They are one of the largest mammalian multigene families. Here, we report a systematic study of polymorphism of OR genes belonging to the largest fully sequenced OR cluster. The cluster contains 36 OR genes, of which two belong to the vomeronasal 1 (V1-OR) family. The cluster is divided into a major and a minor region at the telomeric end of the HLA complex on chromosome 6. These OR genes could be involved in MHC-related mate preferences. The polymorphism screen was carried out with 13 genes from the HLA-linked OR cluster and three genes from chromosomes 7, 17, and 19 as controls. Ten human cell lines, representing 18 different chromosome 6s, were analyzed. They were from various ethnic origins and exhibited different HLA haplotypes. All OR genes tested, including those not linked to the HLA complex, were polymorphic. These polymorphisms were dispersed along the coding region and resulted in up to seven alleles for a given OR gene. Three polymorphisms resulted either in stop codons (genes hs6M1-4P, hs6M1-17) or in a 16–bp deletion (gene hs6M1-19P), possibly leading to lack of ligand recognition by the respective receptors in the cell line donors. In total, 13 HLA-linked OR haplotypes could be defined. Therefore, allelic variation appears to be a general feature of human OR genes.

H. A. Erlich, G. Opelz, and J. Hansen : Immunity, Vol. 14, 347–356, April 2001

HLA DNA Typing and Transplantation : Review

Daniel E. Geraghty, Ji Pei, Brian Lipsky, John A. Hansen, Patricia Taillon-Millers, Sarah K. Bronson and David D. Chaplin : Proc. Natl. Acad. Sci. USA, Vol. 89, pp. 2669-2673, April 1992, Immunology

Cloning and physical mapping of the HLA class I region spanning the HLA-E-to-HLA-F interval by using yeast artificial chromosomes

ABSTRACT : The HLA class I genes are located within a 2-million-base pair (2-Mbp) region constituting the telomeric half of the human major histocompatibility complex. The large majority of the class I sequences, including the lLA-A, -E, -F, and -G genes, is found within the telomeric 1 Mbp. We report here the isolation and characterization of yeast artificial chromosome (YAC) clones that span a contiguous region of >1.2 Mbp and include 14 of the 18 characterized class I sequences. Restriction enzyme mapping and the use of locus-specific probes have allowed all of the class I genes and sequences to be ordered and positioned within the region. In addition, the transcriptional orientation of the four class I genes has been determined. Using probes derived from the ends ofYAC inserts and from class I pseudogenes, we describe a highly polymorphic region between the HLA-A and HLA-G genes. This region appears to be deleted in certainHLA haplotypes, shortening the distance between HLA-A and HL4-G by >50 kilobase pairs (kbp). As part of the characterization of the YAC clones, unique sequence probes derived from the ends of each YAC insert were identified. When combined with probes derived from HLA genes and pseudogenes, 25 locus-specific probes spanning the 1.2-Mbp region have been identified for an average of 1 probe every 48 kbp.

Yasuo Ihara, Kenichi Aoki, Katsushi Tokunaga, Koki Takahashi, and Takeo Juji : Anthropological Science 108(2), 2000, pp. 199-214.

HLA and human mate choice: tests on Japanese couples

ABSTRACT : House mice are apparently more likely to mate with individuals dissimilar to themselves at MHC (major histocompatibility complex) loci than with similar individuals. Such negative assortative mating is thought to be mediated by olfaction. Recently, it has been suggested that human mate choice may be affected by HLA (human leukocyte antigen; MHC in humans), based on the finding that women prefer the odor of men dissimilar to themselves at HLA loci to that of HLA-similar men. If these odor preferences are indeed an important criterion of mate choice in humans, actual marriages may show negative assortment with respect to HLA. In this paper, we compared the observed similarity between spouses at HLA loci with the expected similarity under random mating, for about 150 couples from 6 prefectures in the Tohoku region of Japan, and for about 300 couples from 16 prefectures all over Japan. For statistical tests, we used empirical distributions of goodness-of-fit statistics, X2 and G, obtained by Monte Carlo methods, because these statistics may not follow the chi-square distribution. Tests for each sample as a whole and for each prefecture rule out strong disassortative mating at the HLA-A and HLA-C loci.

Seppo Kuukasjärvi, C. J. Peter Eriksson, Esa Koskela, Tapio Mappes, Kari Nissinen, and Markus J. Rantala : Behavioral Ecology Vol. 15 No. 4: 579–584

Attractiveness of women’s body odors over the menstrual cycle: the role of oral contraceptives and receiver sex

ABSTRACT : It is a long held assumption that women have concealed ovulation, which means that men do not know when women’s menstrual cycles are in their most fertile phase. Recent empirical results have provided evidence that ovulation may not be totally concealed from pair-bonded males, but the generality and the mechanisms of the finding demand further study. To examine the possible adaptive value of the phenomenon, it is necessary to study whether the ability to detect ovulation is confined to males. We studied these questions in an experiment in which male and female raters rated the sexual attractiveness and intensity of T-shirts’ odors worn by 42 women using oral contraceptives (pill users) and by 39 women without oral contraceptives (nonusers). Males rated the sexual attractiveness of nonusers highest at midcycle. However, female raters showed only a nonsignificant trend for this relationship. Neither sex rated attractiveness of the odors of pill users according to their menstrual cycle. The results indicate that men can use olfactory cues to distinguish between ovulating and nonovulating women. Furthermore, the contrasting results between pill users and nonusers may indicate that oral contraceptives demolish the cyclic attractiveness of odors. Together, these findings give more basis for the study of the role of odors in human sexual behavior. Key words: body odor, concealed ovulation,

Keywords : Homo sapiens, human, oral contraceptives, reproductive status, sexual selection.

Manfred Milinski and Claus Wedekind : Behavioral Ecology Vol. 12 No. 2: 140–149

Evidence for MHC-correlated perfume preferences in humans

ABSTRACT : Fragrances have been used since at least 5000 years ago and all traditional scents are found in modern perfumes. Although perfumes are obviously involved in sexual communication, the significance of great individual differences in preference for fragrances is an evolutionary puzzle. The major histocompatibility complex (MHC) is a highly polymorphic and conserved set of genes that plays an important role in immune function in vertebrates. Both mice and humans have been shown to prefer the body odor of potential partners that have a dissimilar MHC genotype, which would result in heterozygous offspring. We tested whether individual preferences for perfume ingredients correlate with a person’s MHC genotype. The human MHC is called HLA (human leukocyte antigen). A total of 137 male and female students who had been typed for their MHC (HLA-A, -B, -DR) scored 36 scents in a first test for use on self (‘‘Would you like to smell like that yourself?’’) and a subset of 18 scents 2 years later either for use on self or for a potential partner (‘‘Would you like your partner to smell like that?’’). An overall analysis showed a significant correlation between the MHC and the scorings of the scents ‘‘for self’’ in both tests. In a detailed analysis we found a significant interaction of the two most common HLAs with the rating of the 36 scents in the first study as well as with the 18 scents in the second study when evaluated for self. This result suggests that persons who share, for example, HLA-A2, have a similar preference for any of the perfume ingredients. The significant repeatability of these preferences in the two tests showed that the volunteers that had either HLA-A1 or HLA-A2 were significantly consistent in their preferences for the perfume ingredients offered. Hardly any significant correlation between MHC genotype and ratings of the scents ‘‘for partner’’ were found. This agrees with the hypothesis that perfumes are selected ‘‘for self’’ to amplify in some way body odors that reveal a person’s immunogenetics.

Keywords : HLA type, immunogenetics, major histocompatibility complex (MHC), perfume, scent preference, sexual communication.

Carole Ober, Lowell R. Weitkamp, Nancy Cox, Harvey Dytch, Donna Kostyu and Sherman Elias : Am. J. Hum. Genet. 61:497-504, 1997

HLA and Mate Choice in Humans

Evidence from studies in rodents suggests that mate selection is influenced by major-histocompatibility-complex haplotypes, with preferences for dissimilar partners. This study was initiated to determine whether avoidance of a mate with the same HLA haplotype as one's own might be occurring in the Hutterites, a North American reproductive isolate of European ancestry, notable for their large sibships, communal lifestyle, and limited number of five-locus HLA haplotypes (HLA-A, -B, -C, -DR, and -DQ). HLA haplotypes were known for 411 Hutterite couples. The number of couples expected to match for a haplotype was calculated in two ways: first, from population genotype frequencies, with account being taken of the nonrandom mating pattern with respect to colony lineages, and, second, from computer simulations using conservative founder assumptions and the exact genealogy of the 411 couples. We observed fewer matches for HLA haplotypes between spouses than expected (first method, P = .005; second method, P = .020-.067). Among couples who did match for a haplotype, the matched haplotype was inherited from the mother in 29 cases and from the father in 50 cases (P = .018). These results are consistent with the conclusion that Hutterite mate choice is influenced by HLA haplotypes, with an avoidance of spouses with haplotypes that are the same as one's own.

Michele L. Schaefer, David A. Young, and Diego Restrepo : The Journal of Neuroscience, April 1, 2001, 21(7):2481–2487

Olfactory Fingerprints for Major Histocompatibility Complex-Determined Body Odors

ABSTRACT : Recognition of individual body odors is analogous to human face recognition in that it provides information about identity. Individual body odors determined by differences at the major histocompatibility complex (MHC or H-2) have been shown to influence mate choice, pregnancy block, and maternal behavior in mice. Unfortunately, the mechanism and extent of the main olfactory bulb (MOB) and accessory olfactory bulb (AOB) involvement in the discrimination of animals according to H-2- type has remained ambiguous. Here we study the neuronal activation patterns evoked in the MOB in different individuals on exposure to these complex, biologically meaningful sensory stimuli. We demonstrate that body odors from H-2 disparate mice evoke overlapping but distinct maps of neuronal activation in the MOB. The spatial patterns of odor-evoked activity are sufficient to be used like fingerprints to predict H-2 identity using a novel computer algorithm. These results provide functional evidence for discrimination of H-2-determined body odors in the MOB, but do not preclude a role for the AOB. These data further our understanding of the neural strategies used to decode socially relevant odors.

Key words: major histocompatibility complex; congenic mice; olfactory; urine; coding; recognition; c-fos; complex odors; mapping

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