Comparative analysis of the human saliva microbiome from different climate zones: Alaska, Germany, and Africa

Background: Although the importance of the human oral microbiome for health and disease is increasingly recognized, variation in the composition of the oral microbiome across different climates and geographic regions is largely unexplored. Results: Here we analyze the saliva microbiome from native Alaskans (76 individuals from 4 populations), Germans (10 individuals from 1 population), and Africans (66 individuals from 3 populations) based on next-generation sequencing of partial 16S rRNA gene sequences. After quality filtering, a total of 67,916 analyzed sequences resulted in 5,592 OTUs (defined at ≥97% identity) and 123 genera. The three human groups differed significantly by the degree of diversity between and within individuals (e.g. beta diversity: Africans > Alaskans > Germans; alpha diversity: Germans > Alaskans > Africans). UniFrac, network, ANOSIM, and correlation analyses all indicated more similarities in the saliva microbiome of native Alaskans and Germans than between either group and Africans. The native Alaskans and Germans also had the highest number of shared bacterial interactions. At the level of shared OTUs, only limited support for a core microbiome shared across all three continental regions was provided, although partial correlation analysis did highlight interactions involving several pairs of genera as conserved across all human groups. Subsampling strategies for compensating for the unequal number of individuals per group or unequal sequence reads confirmed the above observations. Conclusion: Overall, this study illustrates the distinctiveness of the saliva microbiome of human groups living under very different climatic conditions

Comparative analysis of the human saliva microbiome from different climate zones: Alaska, Germany, and Africa

Background: Although the importance of the human oral microbiome for health and disease is increasingly recognized, variation in the composition of the oral microbiome across different climates and geographic regions is largely unexplored. Results: Here we analyze the saliva microbiome from native Alaskans (76 individuals from 4 populations), Germans (10 individuals from 1 population), and Africans (66 individuals from 3 populations) based on next-generation sequencing of partial 16S rRNA gene sequences. After quality filtering, a total of 67,916 analyzed sequences resulted in 5,592 OTUs (defined at ≥97% identity) and 123 genera. The three human groups differed significantly by the degree of diversity between and within individuals (e.g. beta diversity: Africans > Alaskans > Germans; alpha diversity: Germans > Alaskans > Africans). UniFrac, network, ANOSIM, and correlation analyses all indicated more similarities in the saliva microbiome of native Alaskans and Germans than between either group and Africans. The native Alaskans and Germans also had the highest number of shared bacterial interactions. At the level of shared OTUs, only limited support for a core microbiome shared across all three continental regions was provided, although partial correlation analysis did highlight interactions involving several pairs of genera as conserved across all human groups. Subsampling strategies for compensating for the unequal number of individuals per group or unequal sequence reads confirmed the above observations. Conclusion: Overall, this study illustrates the distinctiveness of the saliva microbiome of human groups living under very different climatic conditions. Electronic supplementary material The online version of this article (doi:10.1186/s12866-014-0316-1) contains supplementary material, which is available to authorized users

MtDNA and Y-chromosome variation in Kurdish groups

In order to investigate the origins and relationships of Kurdish-speaking groups, mtDNA HV1 sequences, eleven Y chromosome bi-allelic markers, and 9 Y-STR loci were analyzed among three Kurdish groups: Zazaki and Kurmanji speakers from Turkey, and Kurmanji speakers from Georgia. When compared with published data from other Kurdish groups and from European, Caucasian, and West and Central Asian groups, Kurdish groups are most similar genetically to other West Asian groups, and most distant from Central Asian groups, for both mtDNA and the Y-chromosome. However, Kurdish groups show a closer relationship with European groups than with Caucasian groups based on mtDNA, but the opposite based on the Y-chromosome, indicating some differences in their maternal and paternal histories. The genetic data indicate that the Georgian Kurdish group experienced a bottleneck effect during their migration to the Caucasus, and that they have not had detectable admixture with their geographic neighbours in Georgia. Our results also do not support the hypothesis of the origin of the Zazaki -speaking group being in northern Iran; genetically they are more similar to other Kurdish groups. Genetic analyses of recent events, such as the origins and migrations of Kurdish-speaking groups, can therefore lead to new insights into such migrations. [References: 48

Global diversity in the human salivary microbiome

The human salivary microbiome may play a role in diseases of the oral cavity and interact with microbiomes from other parts of the human body (in particular, the intestinal tract), but little is known about normal variation in the salivary microbiome. We analyzed 14,115 partial (∼500 bp) 16S ribosomal RNA (rRNA) sequences from saliva samples from 120 healthy individuals (10 individuals from each of 12 worldwide locations). These sequences could be assigned to 101 known bacterial genera, of which 39 were not previously reported from the human oral cavity; phylogenetic analysis suggests that an additional 64 unknown genera are present. There is high diversity in the salivary microbiome within and between individuals, but little geographic structure. Overall, ∼13.5% of the total variance in the composition of genera is due to differences among individuals, which is remarkably similar to the fraction of the total variance in neutral genetic markers that can be attributed to differences among human populations. Investigation of some environmental variables revealed a significant association between the genetic distances among locations and the distance of each location from the equator. Further characterization of the enormous diversity revealed here in the human salivary microbiome will aid in elucidating the role it plays in human health and disease, and in the identification of potentially informative species for studies of human population history

The contribution of rare variation to prostate cancer heritability

We report targeted sequencing of 63 known prostate cancer risk regions in a multi-ancestry study of 9,237 men and use the data to explore the contribution of low-frequency variation to disease risk. We show that SNPs with minor allele frequencies (MAFs) of 0.1–1% explain a substantial fraction of prostate cancer risk in men of African ancestry. We estimate that these SNPs account for 0.12 (standard error (s.e.) = 0.05) of variance in risk (∼42% of the variance contributed by SNPs with MAF of 0.1–50%). This contribution is much larger than the fraction of neutral variation due to SNPs in this class, implying that natural selection has driven down the frequency of many prostate cancer risk alleles; we estimate the coupling between selection and allelic effects at 0.48 (95% confidence interval [0.19, 0.78]) under the Eyre-Walker model. Our results indicate that rare variants make a disproportionate contribution to genetic risk for prostate cancer and suggest the possibility that rare variants may also have an outsize effect on other common traits

Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk

Prostate cancer is the most common non-skin cancer in males, with a ∼1.5–2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(−6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(−5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(−4)) and GORAB (P = 2.3 × 10(−4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case–control or case–case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5–1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk