Etude des polymorphismes génétiques des systèmes HLA, GM, ADN mitochondrial et chromosome Y dans les populations vietnamiennes

Nous avons étudié la diversité génétique de trois populations dans le contexte multiethnique complexe du Viêt Nam: les Cham (Austronésiens), les Khmer (Austroasiatiques) et les Nung (Taï-Kadaï). Pour cela, quatre systèmes génétiques indépendants ont été analysés: le système HLA (loci A, B, C, DRB1 et DPB1), la région HVS1 de l'ADN mitochondrial, le chromosome Y (SNPs et STRs) et le système GM. Les profils génétiques de ces populations ont été comparés à d'autres populations de la région sud-est asiatique. Nos résultats montrent que la diversité génétique des populations vietnamiennes est corrélée avec leur localisation géographique. La proximité génétique observée entre Cham et Khmer soutient l'hypothèse d'une diffusion des langues Austronésiennes dans la région, alors que la faible diversité de la population Nung révèle un isolement important. Les résultats, concordants entre 4 systèmes indépendants, confirment que le polymorphisme HLA conserve les principaux signaux de l'histoire démographique humaine à une échelle sub-continentale

Allele frequency estimation from ambiguous data : using resampling schema in validating frequency estimates and in selective neutrality testing

The development of molecular typing techniques applied to the study of population genetic diversity originates data with increasing precision but at the cost of some ambiguities. As distinct techniques may produce distinct kinds of ambiguities, a crucial issue is to assess the differences between frequency distributions estimated from data produced by alternative techniques for the same sample. To that aim, we developed a resampling scheme that allows evaluating, by statistical means, the significance of the difference between two frequency distributions. The same approach is then shown to be applicable to test selective neutrality when only sample frequencies are known. The use of these original methods is presented here through an application to the genetic study of a Munda human population sample, where three different HLA loci were typed using two different molecular methods (reverse PCR-SSO typing on microbeads arrays based on Luminex technology and PCR-SSP typing), as described in details in the companion article by Riccio et al. [The Austroasiatic Munda population from India and its enigmatic origin: An HLA diversity study. Hum. Biol. 38:405–435 (2011)]. The differences between the frequency estimates of the two typing techniques were found to be smaller than those resulting from sampling. Overall, we show that using a resampling scheme in validating frequency estimates is effective when alternative frequency estimates are available. Moreover, resampling appears to be the unique way to test selective neutrality when only frequency data are available to describe the genetic structure of populations

The Austroasiatic Munda Population from India and its Enigmatic Origin: A HLA Diversity Study

The Austroasiatic linguistic family disputes its origin between two geographically distant regions of Asia, India, and Southeast Asia, respectively. As genetic studies based on classical and gender-specific genetic markers provided contradictory results to this debate thus far, we investigated the HLA diversity (HLA-A, -B, and –DRB1 loci) of an Austroasiatic Munda population from Northeast India and its relationships with other populations from India and Southeast Asia. Because molecular methods currently used to test HLA markers often provide ambiguous results due to the high complexity of this polymorphism, we applied two different techniques (reverse PCR-SSO typing on microbeads arrays based on Luminex technology, and PCR-SSP typing) to type the samples. After validating the resulting frequency distributions through the original statistical method described in our companion article (Nunes et al. 2011), we compared the HLA genetic profile of the sampled Munda to those of other Asiatic populations, among which Dravidian and Indo-European-speakers from India and populations from East and Southeast Asia speaking languages belonging to different linguistic families

Household carriage and acquisition of extended-spectrum β-lactamase–producing Enterobacteriaceae: A systematic review

The epidemiology of ESBL-producing Enterobacteriaceae (ESBL-PE) has been extensively studied in hospitals, but data on community transmission are scarce. We investigated ESBL-PE cocarriage and acquisition in households using a systematic literature review

16th IHIW: Analysis of HLA Population Data, with updated results for 1996 to 2012 workshop data (AHPD project report)

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May–June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy–Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th–15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution

Gut microbiome dynamics in index patients colonized with extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales after hospital discharge and their household contacts

Colonization with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) often precedes infections and is therefore considered as a great threat for public health. Here, we studied the gut microbiome dynamics in eight index patients colonized with ESBL-PE after hospital discharge and the impact of exposure to this index patient on the gut microbiome dynamics of their household contacts. We showed that the microbiome composition from index patients is different from their household contacts upon hospital discharge and that, in some of the index patients, their microbiome composition over time shifted toward the composition of their household contacts. In contrast, household contacts showed a stable microbiome composition over time irrespective of low-level extended-spectrum beta-lactamase-producingEscherichia coli(ESBL-Ec) or extended-spectrum beta-lactamase-producingKlebsiella pneumoniae(ESBL-Kp) gut colonization, suggesting that, in healthy microbiomes, colonization resistance is able to prevent ESBL-PE expansion

Norwegian Sami differs significantly from other Norwegians according to their HLA profile

This study reports extensive genomic data for both human leukocyte antigen (HLA) class I and II loci in Norwegian Sami, a native population living in the northwest of Europe. The Sami have a distinct culture and their own languages, which belong to the Uralic linguistic family. Norwegian Sami (n = 200) were typed at the DNA level for the HLA-A, -C, -B, -DRB1 and -DQB1 loci, and compared with a non- Sami Norwegian population (n = 576). The two populations exhibited some common genetic features but also differed significantly at all HLA loci. The most significantly deviating allele frequencies were an increase of HLA-A*03, -B*27, -DRB1*08 and -DQB1*04 and a decrease of HLA-A*01, C*01, -DRB1*04 and -DQB1*02 among Sami compared with non-Sami Norwegians. The Sami showed no deviation from Hardy–Weinberg equilibrium. The hypothesis of selective neutrality was rejected at all loci except for the A- and C- loci for the Sami. HLA haplotype frequencies also differed between the two populations. The most common extended HLA haplotypes were A*02-B*27-C*01-DR*08-DQB1*04 in the Sami and A*01-B*08-C*07-DR*03- DQB1*02 in the other Norwegians. Genetic distance analyses indicated that theNorwegian Sami were highly differentiated from other Europeans and were most closely related to Finns whose language also belongs to the Uralic linguistic family. In conclusion, the Norwegian Sami and the non-Sami Norwegians were significantly different at all HLA loci. Our results can be explained by the fact that the two populations have different origins and that the Sami population has remained smaller and more isolated than its neighbors

Household acquisition and transmission of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae after hospital discharge of ESBL-positive index patients

Objectives: This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient. Methods: Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis

Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report)

During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy–Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1–7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies