Toward a more uniform sampling of human genetic diversity: A survey of worldwide populations by high-density genotyping

Xing, Jinchuan; Watkins, W. Scott; Shlien, Adam; Walker, Erin J.; Huff, Chad; Witherspoon, David J.; Zhang, Yuhua; Simonson, Tatum S.; Weiss, Robert B.; Schiffman, Joshua D.; Malkin, David; Woodward, Scott R.; Jorde, Lynn B.

doi:10.1016/j.ygeno.2010.07.004

Cited by 78 publications

(110 citation statements)

References 66 publications

(75 reference statements)

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“…The dashed LOESS fitted line highlights the significant negative correlation between the two variables, as assessed by the Spearman's rank correlation test. Although one Oceanic sample (Tongan/Samoan) appears as an outlier, its allele frequency (19%) is consistent with this sample's previously reported genetic relationship to East Asians (Xing et al 2010). ( largely consistent with demographic models of the human expansion out of Africa, with a potential weak contribution from positive/ negative selection.…”

Section: Population Stratification Of the 8p23 Inversionsupporting

confidence: 84%

“…Following PFIDO, samples were regrouped as recommended (Donnelly et al 2010;Xing et al 2010) to mitigate sampling error. Six populations with sample sizes less than 10 and two populations in which inversion-allele frequency breached HWE (exact test; P < 0.05) were excluded.…”

Section: Global 8p23 Inversion Distributionmentioning

confidence: 99%

“…Populations in the study by Xing et al (2010) and in HapMap were geographically assigned to their sampling location, apart from CEU and CHD samples (assigned to Northern Europe and Eastern China, respectively) (Lao et al 2008;International HapMap 3 Consortium 2010). Chinese SGVP samples were assigned to Southern China (Teo et al 2009), whereas SGVP Malay and Indian populations were placed in their country of origin's center.…”

Section: Global 8p23 Inversion Distributionmentioning

confidence: 99%

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The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism

Salm

Horswell²,

Hutchison³

et al. 2012

Genome Res.

159

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Genomic inversions are an increasingly recognized source of genetic variation. However, a lack of reliable high-throughput genotyping assays for these structures has precluded a full understanding of an inversion's phylogenetic, phenotypic, and population genetic properties. We characterize these properties for one of the largest polymorphic inversions in man (the ∼4.5-Mb 8p23.1 inversion), a structure that encompasses numerous signals of natural selection and disease association. We developed and validated a flexible bioinformatics tool that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion. This tool was applied retrospectively to diverse genome-wide data sets, revealing significant population stratification that largely follows a clinal “serial founder effect” distribution model. Phylogenetic analyses establish the inversion's ancestral origin within the Homo lineage, indicating that 8p23.1 inversion has occurred independently in the Pan lineage. The human inversion breakpoint was localized to an inverted pair of human endogenous retrovirus elements within the large, flanking low-copy repeats; experimental validation of this breakpoint confirmed these elements as the likely intermediary substrates that sponsored inversion formation. In five data sets, mRNA levels of disease-associated genes were robustly associated with inversion genotype. Moreover, a haplotype associated with systemic lupus erythematosus was restricted to the derived inversion state. We conclude that the 8p23.1 inversion is an evolutionarily dynamic structure that can now be accommodated into the understanding of human genetic and phenotypic diversity.

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Section: Population Stratification Of the 8p23 Inversionsupporting

confidence: 84%

Section: Global 8p23 Inversion Distributionmentioning

confidence: 99%

Section: Global 8p23 Inversion Distributionmentioning

confidence: 99%

See 1 more Smart Citation

The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism

Salm

Horswell²,

Hutchison³

et al. 2012

Genome Res.

159

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“…Uniform global sample 36 This data were downloaded on 6/20/15 from http://jordelab.genetics.utah.edu/pub/affy6_xing2010/. Sampling locations were provided by Jinchuan Xing.…”

Section: Estonian Biocentre Datamentioning

confidence: 99%

Genetic landscapes reveal how human genetic diversity aligns with geography

Peter

Petkova

Novembre

2017

Preprint

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Geographic patterns in human genetic diversity carry footprints of population history 1,2 and need to be understood to carry out global biomedicine 3,4 . Summarizing and visually representing these patterns of diversity has been a persistent goal for human geneticists [5][6][7][8][9] . However, most analytical methods to represent population structure [10][11][12][13][14] do not incorporate geography directly, and it must be considered post hoc alongside a visual summary. Here, we use a recently developed spatially explicit method to estimate "effective migration" surfaces to visualize how human genetic diversity is geographically structured (the EEMS method 15). The resulting surfaces are "rugged", which indicates the relationship between genetic and geographic distance is heterogenous and distorted as a rule. Most prominently, topographic and marine features regularly align with increased genetic differentiation (e.g. the Sahara Desert, Mediterranean Sea or Himalaya at large scales; the Adriatic, inter-island straits in near Oceania at smaller scales). We also see traces of historical migrations and boundaries of language families. These results provide visualizations of human genetic diversity that reveal local patterns of differentiation in detail and emphasize that while genetic similarity generally decays with geographic distance, there have regularly been factors that subtly distort the underlying relationship across space observed today. The fine-scale population structure depicted here is relevant to understanding complex processes of human population history and may provide insights for geographic patterning in rare variants and heritable disease risk.In many regions of the world, genetic diversity "mirrors" geography in the sense that genetic differentiation increases with geographic distance ("isolation by distance" [16][17][18] ); However, due to the complexities of geography and history, this relationship is not one of constant proportionality. The recently developed analysis method EEMS visualizes how the isolation-by-distance relationship varies across geographic space 15 Specifically, it uses a model based on a local "effective migration" rate. For several reasons, the effective migration rates inferred by EEMS do not directly represent levels of gene flow 15 ; however they are useful for conveying spatial population structure: high values of effective migration reflect genetic isolation accrues gradually with distance, and low values imply isolation accrues rapidly with distance. In turn, a map of inferred patterns of effective migration can provide a compact visualization of spatial genetic structure for large, complex samples. 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/233486 doi: bioRxiv preprint first posted online Dec. ...

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“…However, traditional methods are not always the most effective as each person has a different genetic architecture (1). Recent advances in medical and human genetics have enabled a more detailed understanding of the impact of genetics in disease (2).…”

Section: Introductionmentioning

confidence: 99%

Overview of personalized medicine in the disease genomic era

Hong¹,

Oh²

2010

BMB Reports

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Sir William Osler (1849-1919) recognized that "variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions we know as disease". Accordingly, the traditional methods of medicine are not always best for all patients. Over the last decade, the study of genomes and their derivatives (RNA, protein and metabolite) has rapidly advanced to the point that genomic research now serves as the basis for many medical decisions and public health initiatives. Genomic tools such as sequence variation, transcription and, more recently, personal genome sequencing enable the precise prediction and treatment of disease. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. In order to make personalized medicine effective, these genomic techniques must be standardized and integrated into health systems and clinical workflow. In addition, full application of personalized or genomic medicine requires dramatic changes in regulatory and reimbursement policies as well as legislative protection related to privacy. This review aims to provide a general overview of these topics in the field of personalized medicine. [BMB reports 2010; 43(10): 643-648]

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Toward a more uniform sampling of human genetic diversity: A survey of worldwide populations by high-density genotyping

Cited by 78 publications

References 66 publications

The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism

The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism

Genetic landscapes reveal how human genetic diversity aligns with geography

Overview of personalized medicine in the disease genomic era

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