scholarly journals Topological linkage disequilibrium calculated from coalescent genealogies

2018 ◽  
Author(s):  
Johannes Wirtz ◽  
Martina Rauscher ◽  
Thomas Wiehe
Keyword(s):  
Linkage Disequilibrium ◽  
Coefficient Of Variation ◽  
Human Populations ◽  
Classical Concept ◽  
Practical Application ◽  
Natural Measure ◽  
Marker Loci ◽  
Rate Of Decay ◽  
Coalescent Tree

AbstractWe revisit the classical concept of two-locus linkage disequilibrium (LD) and introduce a novel way of looking at haplotypes. In contrast to defining haplotypes as allele combinations at two marker loci, we concentrate on the clustering of sampled chromosomes induced by their coalescent genealogy. The root of a binary coalescent trees defines two clusters of chromosomes. At two different loci this assignment may be different as a result of recombination. We show that the amount of shared chromosomes among clusters at two different loci, measured by the squared correlation, constitutes a natural measure of LD. We call this topological LD (tLD) since it is induced by the topology of the coalescent tree. We find that its rate of decay decreases more slowly with distance between loci than that of conventional LD. Furthermore, tLD has a smaller coefficient of variation, which should render it more accurate for any kind of mapping purposes than conventional LD. We conclude with a practical application to the LCT region in human populations.

scholarly journals Different historical generation intervals in human populations inferred from Neanderthal fragment lengths and patterns of mutation accumulation

2021 ◽  
Author(s):  
Moisès Coll Macià ◽  
Laurits Skov ◽  
Benjamin Marco Peter ◽  
Mikkel Heide Schierup
Keyword(s):  
Fragment Length ◽  
Human Populations ◽  
Female Age ◽  
Generation Interval ◽  
The Past ◽  
Geographical Regions ◽  
Neanderthal Admixture ◽  
Rate Of Decay ◽  
Out Of Africa ◽  
Insight Into

AbstractAfter the main out-of-Africa event, humans interbred with Neanderthals leaving 1-2% of Neanderthal DNA scattered in small fragments in all non-African genomes today1,2. Here we investigate the size distribution of these fragments in non-African genomes3. We find consistent differences in fragment length distributions across Eurasia with 11% longer fragments in East Asians than in West Eurasians. By comparing extant populations and ancient samples, we show that these differences are due to a different rate of decay in length by recombination since the Neanderthal admixture. In line with this, we observe a strong correlation between the average fragment length and the accumulation of derived mutations, similar to what is expected by changing the ages at reproduction as estimated from trio studies4. Altogether, our results suggest consistent differences in the generation interval across Eurasia, by up to 20% (e.g. 25 versus 30 years), over the past 40,000 years. We use sex-specific accumulations of derived alleles to infer how these changes in generation intervals between geographical regions could have been mainly driven by shifts in either male or female age of reproduction, or both. We also find that previously reported variation in the mutational spectrum5 may be largely explained by changes to the generation interval and not by changes to the underlying mutational mechanism. We conclude that Neanderthal fragment lengths provide unique insight into differences of a key demographic parameter among human populations over the recent history.

scholarly journals Genomic and demographic processes differentially influence genetic variation across the X chromosome

2021 ◽  
Author(s):  
Daniel J. Cotter ◽  
Timothy H. Webster ◽  
Melissa A. Wilson
Keyword(s):  
Genetic Diversity ◽  
Genetic Variation ◽  
Linkage Disequilibrium ◽  
X Chromosome ◽  
Global Scale ◽  
Careful Consideration ◽  
Human Populations ◽  
Evolutionary Forces ◽  
Ideal System ◽  
Demographic Patterns

AbstractMutation, recombination, selection, and demography affect genetic variation across the genome. Increased mutation and recombination both lead to increases in genetic diversity in a region-specific manner, while complex demographic patterns shape patterns of diversity on a more global scale. The X chromosome is particularly interesting because it contains several distinct regions that are subject to different combinations and strengths of these processes, notably the pseudoautosomal regions (PARs) and the X-transposed region (XTR). The X chromosome thus can serve as a unique model for studying how genetic and demographic forces act in different contexts to shape patterns of observed variation. Here we investigate diversity, divergence, and linkage disequilibrium in each region of the X chromosome using genomic data from 26 human populations. We find that both diversity and substitution rate are consistently elevated in PAR1 and the XTR compared to the rest of the X chromosome. In contrast, linkage disequilibrium is lowest in PAR1 and highest on the non-recombining X chromosome, with the XTR falling in between, suggesting that the XTR (usually included in the non-recombining X) may need to be considered separately in future studies. We also observed strong population-specific effects on genetic diversity; not only does genetic variation differ on the X and autosomes among populations, but the effects of linked selection on the X relative to autosomes have been shaped by population-specific history. The substantial variation in patterns of variation across these regions provides insight into the unique evolutionary history contained within the X chromosome.Significance StatementDemography and selection affect the X chromosome differently from non-sex chromosomes. However, the X chromosome can be subdivided into multiple distinct regions that facilitate even more fine-scaled assessment of these processes. Here we study regions of the human X chromosome in 26 populations to find evidence that recombination may be mutagenic in humans and that the X-transposed region may undergo recombination. Further we observe that the effects of selection and demography act differently on the X chromosome relative to the autosomes across human populations. Together, our results highlight profound regional differences across the X chromosome, simultaneously making it an ideal system for exploring the action of evolutionary forces as well as necessitating its careful consideration and treatment in genomic analyses.

scholarly journals Terc Gene Cluster Variants Predict Liver Telomere Length in Mice

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2623
Author(s):  
Dana Zeid ◽  
Sean Mooney-Leber ◽  
Laurel R. Seemiller ◽  
Lisa R. Goldberg ◽  
Thomas J. Gould
Keyword(s):  
Linkage Disequilibrium ◽  
Telomere Length ◽  
Gene Cluster ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Chromosome 3 ◽  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Initial Finding

Variants in a gene cluster upstream-adjacent to TERC on human chromosome 3, which includes genes APRM, LRRC31, LRRC34 and MYNN, have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the TERC gene cluster influence telomere length in humans is unknown. Given the proximity between the TERC gene cluster and TERC (~0.05 Mb) in humans, it is speculated that cluster variants are in linkage disequilibrium with a TERC causal variant. In mice, the Terc gene/Terc gene cluster are also located on chromosome 3; however, the Terc gene cluster is located distantly downstream of Terc (~60 Mb). Here, we initially aim to investigate the interactions between genotype and nicotine exposure on absolute liver telomere length (aTL) in a panel of eight inbred mouse strains. Although we found no significant impact of nicotine on liver aTL, this first experiment identified candidate single nucleotide polymorphisms (SNPs) in the murine Terc gene cluster (within genes Lrrc31, Lrriq4 and Mynn) co-varying with aTL in our panel. In a second experiment, we tested the association of these Terc gene cluster variants with liver aTL in an independent panel of eight inbred mice selected based on candidate SNP genotype. This supported our initial finding that Terc gene cluster polymorphisms impact aTL in mice, consistent with data in human populations. This provides support for mice as a model for telomere dynamics, especially for studying mechanisms underlying the association between Terc cluster variants and telomere length. Finally, these data suggest that mechanisms independent of linkage disequilibrium between the Terc/TERC gene cluster and the Terc/TERC gene mediate the cluster’s regulation of telomere length.

scholarly journals Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Reuben J. Pengelly ◽  
William Tapper ◽  
Jane Gibson ◽  
Marcin Knut ◽  
Rick Tearle ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Human Populations ◽  
Whole Genome ◽  
Linkage Disequilibrium Structure ◽  
Genome Sequences

scholarly journals Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium

Genetics ◽  
2013 ◽  
Vol 193 (4) ◽  
pp. 1233-1254 ◽  
Author(s):  
Po-Ru Loh ◽  
Mark Lipson ◽  
Nick Patterson ◽  
Priya Moorjani ◽  
Joseph K. Pickrell ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Human Populations

scholarly journals Methodology of expert evaluation of effectiveness of methods of organizational diagnostics

2017 ◽  
pp. 38-43
Author(s):  
T. V. CHIBIKOVA
Keyword(s):  
Standard Deviation ◽  
Coefficient Of Variation ◽  
Random Variable ◽  
Diagnostic Methods ◽  
Practical Significance ◽  
Expert Evaluation ◽  
Practical Application ◽  
Actual Problem ◽  
Survey Results ◽  
Statistical Indicators

The article is devoted to the actual problem of assessing the effectiveness of consulting methods. Management consulting is a developing sphere of human activity. The technique of an estimation of efficiency of methods of organizational diagnostics is offered. The research was based on the problem of assessing the effectiveness of diagnostic methods in consulting using only economic indicators. According to the methodology, during the evaluation, the effectiveness of methods is is assessed in the light of costs and results, both should be similarly broken down into a number of elements. These elements were to be evaluated by experts. To confirm the validity of the results obtained, statistical indicators are used: variance of a random variable, standard deviation and coefficient of variation, which confirm (or disprove) the results of an expert poll.To approbate the methodology, a survey of experts elected among employees of consulting companies in Omsk was conducted. The survey data was analyzed. Based on the results of the analysis, the validity of the obtained survey results and the possibility of their practical application was concluded. The practical significance of the study is that it is possible to apply the methodology of interviewing experts in practice. The purpose of such surveys will be a regular reassessment and identification of the need for specific consulting methods for certain methods of organizational diagnostics.

scholarly journals A sex-specific evolutionary interaction between ADCY9 and CETP

2021 ◽  
Author(s):  
Isabel Gamache ◽  
Marc-André Legault ◽  
Jean-Christophe Grenier ◽  
Rocio Sanchez ◽  
Eric Rhéaume ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Epistatic Interaction ◽  
Human Populations ◽  
Uk Biobank ◽  
Rna Seq ◽  
Specific Result ◽  
Transfer Protein ◽  
Clinical Responses ◽  
The Uk ◽  
Pharmacogenomic Studies

Pharmacogenomic studies have revealed associations between rs1967309 in the adenylyl cyclase type 9 (ADCY9) gene and clinical responses to the cholesteryl ester transfer protein (CETP) modulator dalcetrapib, however, the mechanism behind this interaction is still unknown. Here, we characterized selective signals at the locus associated with the pharmacogenomic response in human populations and we show that rs1967309 region exhibits signatures of natural selection in several human populations. Furthermore, we identified a variant in CETP, rs158477, which is in long-range linkage disequilibrium with rs1967309 in the Peruvian population. The signal is mainly seen in males, a sex-specific result that is replicated in the LIMAA cohort of over 3400 Peruvians. We further detected interaction effects of these two SNPs with sex on cardiovascular phenotypes in the UK Biobank, in line with the sex-specific genotype associations found in Peruvians at these loci. Analyses of RNA-seq data further suggest an epistatic interaction on CETP expression levels between the two SNPs in multiple tissues. We propose that ADCY9 and CETP coevolved during recent human evolution, which points towards a biological link between dalcetrapib's pharmacogene ADCY9 and its therapeutic target CETP.

Demographic history and linkage disequilibrium in human populations

1997 ◽  
Vol 17 (4) ◽  
pp. 435-438 ◽  
Author(s):  
Maris Laan ◽  
Svante Pääbo
Keyword(s):  
Linkage Disequilibrium ◽  
Demographic History ◽  
Human Populations

scholarly journals Similar patterns of genetic diversity and linkage disequilibrium in Western chimpanzees (Pan troglodytes verus) and humans indicate highly conserved mechanisms of MHC molecular evolution

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Christelle Vangenot ◽  
José Manuel Nunes ◽  
Gaby M. Doxiadis ◽  
Estella S. Poloni ◽  
Ronald E. Bontrop ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Linkage Disequilibrium ◽  
Molecular Diversity ◽  
Selective Sweep ◽  
Balancing Selection ◽  
Substantial Effect ◽  
Human Populations ◽  
Large Set ◽  
Large Populations ◽  
Population Sizes

Abstract Background Many species are threatened with extinction as their population sizes decrease with changing environments or face novel pathogenic threats. A reduction of genetic diversity at major histocompatibility complex (MHC) genes may have dramatic effects on populations’ survival, as these genes play a key role in adaptive immunity. This might be the case for chimpanzees, the MHC genes of which reveal signatures of an ancient selective sweep likely due to a viral epidemic that reduced their population size a few million years ago. To better assess how this past event affected MHC variation in chimpanzees compared to humans, we analysed several indexes of genetic diversity and linkage disequilibrium across seven MHC genes on four cohorts of chimpanzees and we compared them to those estimated at orthologous HLA genes in a large set of human populations. Results Interestingly, the analyses uncovered similar patterns of both molecular diversity and linkage disequilibrium across the seven MHC genes in chimpanzees and humans. Indeed, in both species the greatest allelic richness and heterozygosity were found at loci A, B, C and DRB1, the greatest nucleotide diversity at loci DRB1, DQA1 and DQB1, and both significant global linkage disequilibrium and the greatest proportions of haplotypes in linkage disequilibrium were observed at pairs DQA1 ~ DQB1, DQA1 ~ DRB1, DQB1 ~ DRB1 and B ~ C. Our results also showed that, despite some differences among loci, the levels of genetic diversity and linkage disequilibrium observed in contemporary chimpanzees were globally similar to those estimated in small isolated human populations, in contrast to significant differences compared to large populations. Conclusions We conclude, first, that highly conserved mechanisms shaped the diversity of orthologous MHC genes in chimpanzees and humans. Furthermore, our findings support the hypothesis that an ancient demographic decline affecting the chimpanzee populations – like that ascribed to a viral epidemic – exerted a substantial effect on the molecular diversity of their MHC genes, albeit not more pronounced than that experienced by HLA genes in human populations that underwent rapid genetic drift during humans’ peopling history. We thus propose a model where chimpanzees’ MHC genes regenerated molecular variation through recombination/gene conversion and/or balancing selection after the selective sweep.

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