Combining Sperm Typing and Linkage Disequilibrium Analyses Reveals Differences in Selective Pressures or Recombination Rates Across Human Populations

Abstract I determine the contribution of linkage disequilibrium to genetic variances using results for two loci and for induced or marginal systems. The analysis allows epistasis and dominance, but assumes that mutation is weak relative to selection. The linkage disequilibrium component of genetic variance is shown to be unimportant for unlinked loci if the gametic mutation rate divided by the harmonic mean of the pairwise recombination rates is much less than one. For tightly linked loci, linkage disequilibrium is unimportant if the gametic mutation rate divided by the (induced) per locus selection is much less than one.

Download Full-text

Modeling Linkage Disequilibrium and Identifying Recombination Hotspots Using Single-Nucleotide Polymorphism Data

Genetics ◽

10.1093/genetics/165.4.2213 ◽

2003 ◽

Vol 165 (4) ◽

pp. 2213-2233 ◽

Cited By ~ 41

Author(s):

Na Li ◽

Matthew Stephens

Keyword(s):

Linkage Disequilibrium ◽

Recombination Rate ◽

Population Sample ◽

Simulated Data ◽

Region Of Interest ◽

Population Data ◽

Recombination Rates ◽

Single Nucleotide ◽

Recombination Hotspots ◽

Genomic Regions

AbstractWe introduce a new statistical model for patterns of linkage disequilibrium (LD) among multiple SNPs in a population sample. The model overcomes limitations of existing approaches to understanding, summarizing, and interpreting LD by (i) relating patterns of LD directly to the underlying recombination process; (ii) considering all loci simultaneously, rather than pairwise; (iii) avoiding the assumption that LD necessarily has a “block-like” structure; and (iv) being computationally tractable for huge genomic regions (up to complete chromosomes). We examine in detail one natural application of the model: estimation of underlying recombination rates from population data. Using simulation, we show that in the case where recombination is assumed constant across the region of interest, recombination rate estimates based on our model are competitive with the very best of current available methods. More importantly, we demonstrate, on real and simulated data, the potential of the model to help identify and quantify fine-scale variation in recombination rate from population data. We also outline how the model could be useful in other contexts, such as in the development of more efficient haplotype-based methods for LD mapping.

Download Full-text

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

10.1101/2021.01.31.429027 ◽

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.

Download Full-text

Recessive deleterious variation has a limited impact on signals of adaptive introgression in human populations

10.1101/2020.01.13.905174 ◽

2020 ◽

Author(s):

Xinjun Zhang ◽

Bernard Kim ◽

Kirk E. Lohmueller ◽

Emilia Huerta-Sánchez

Keyword(s):

False Positive ◽

False Positive Rate ◽

Genomic Variation ◽

Human Populations ◽

Deleterious Mutations ◽

Modern Humans ◽

Recombination Rates ◽

Limited Impact ◽

Adaptive Mutations ◽

Adaptive Introgression

AbstractAdmixture with archaic hominins has altered the landscape of genomic variation in modern human populations. Several gene regions have been previously identified as candidates of adaptive introgression (AI) that facilitated human adaptation to specific environments. However, simulation-based studies have suggested that population genetics processes other than adaptive mutations, such as heterosis from recessive deleterious variants private to populations before admixture, can also lead to patterns in genomic data that resemble adaptive introgression. The extent to which the presence of deleterious variants affect the false-positive rate and the power of current methods to detect AI has not been fully assessed. Here, we used extensive simulations to show that recessive deleterious mutations can increase the false positive rates of tests for AI compared to models without deleterious variants. We further examined candidates of AI in modern humans identified from previous studies and show that, although deleterious variants may hinder the performance of AI detection in modern humans, most signals remained robust when deleterious variants are included in the null model. While deleterious variants may have a limited impact on detecting signals of adaptive introgression in humans, we found that at least two AI candidate genes, HYAL2 and HLA, are particularly susceptible to high false positive rates due to the recessive deleterious mutations. By quantifying parameters that affect heterosis, we show that the high false positives are largely attributed to the high exon densities together with low recombination rates in the genomic regions, which can further be exaggerated by the population growth in recent human evolution. Although the combination of such parameters is rare in the human genome, caution is still warranted in other species with different genomic composition and demographic histories.

Download Full-text

Terc Gene Cluster Variants Predict Liver Telomere Length in Mice

Cells ◽

10.3390/cells10102623 ◽

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.

Download Full-text

Inferring the Genomic Landscape of Recombination Rate Variation in European Aspen (Populus tremula)

G3 Genes|Genome|Genetics ◽

10.1534/g3.119.400504 ◽

2019 ◽

Vol 10 (1) ◽

pp. 299-309 ◽

Cited By ~ 2

Author(s):

Rami-Petteri Apuli ◽

Carolina Bernhardsson ◽

Bastian Schiffthaler ◽

Kathryn M. Robinson ◽

Stefan Jansson ◽

...

Keyword(s):

Linkage Disequilibrium ◽

Linkage Map ◽

Recombination Rate ◽

Gene Density ◽

Populus Tremula ◽

Rate Variation ◽

Recombination Rates ◽

Genomic Features ◽

European Aspen ◽

Recombination Rate Variation

The rate of meiotic recombination is one of the central factors determining genome-wide levels of linkage disequilibrium which has important consequences for the efficiency of natural selection and for the dissection of quantitative traits. Here we present a new, high-resolution linkage map for Populus tremula that we use to anchor approximately two thirds of the P. tremula draft genome assembly on to the expected 19 chromosomes, providing us with the first chromosome-scale assembly for P. tremula (Table 2). We then use this resource to estimate variation in recombination rates across the P. tremula genome and compare these results to recombination rates based on linkage disequilibrium in a large number of unrelated individuals. We also assess how variation in recombination rates is associated with a number of genomic features, such as gene density, repeat density and methylation levels. We find that recombination rates obtained from the two methods largely agree, although the LD-based method identifies a number of genomic regions with very high recombination rates that the map-based method fails to detect. Linkage map and LD-based estimates of recombination rates are positively correlated and show similar correlations with other genomic features, showing that both methods can accurately infer recombination rate variation across the genome. Recombination rates are positively correlated with gene density and negatively correlated with repeat density and methylation levels, suggesting that recombination is largely directed toward gene regions in P. tremula.

Download Full-text

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

BMC Genomics ◽

10.1186/s12864-015-1854-0 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 12

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

Download Full-text

A Multilocus Model for Constructing a Linkage Disequilibrium Map in Human Populations

Statistical Applications in Genetics and Molecular Biology ◽

10.2202/1544-6115.1419 ◽

2009 ◽

Vol 8 (1) ◽

pp. 1-25 ◽

Cited By ~ 10

Author(s):

Qin Li ◽

Rongling Wu

Keyword(s):

Linkage Disequilibrium ◽

Human Populations ◽

Multilocus Model ◽

Linkage Disequilibrium Map

Download Full-text

Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium

Genetics ◽

10.1534/genetics.112.147330 ◽

2013 ◽

Vol 193 (4) ◽

pp. 1233-1254 ◽

Cited By ~ 259

Author(s):

Po-Ru Loh ◽

Mark Lipson ◽

Nick Patterson ◽

Priya Moorjani ◽

Joseph K. Pickrell ◽

...

Keyword(s):

Linkage Disequilibrium ◽

Human Populations

Download Full-text

Human influences on antipredator behaviour in Darwin’s finches

10.1101/591651 ◽

2019 ◽

Cited By ~ 1

Author(s):

Kiyoko M. Gotanda

Keyword(s):

Urban Areas ◽

Antipredator Behaviour ◽

Human Populations ◽

Urban Populations ◽

Darwin's Finches ◽

Selective Pressures ◽

Invasive Predators ◽

Darwin’S Finches ◽

History Of ◽

Predator Eradication

Abstract1) Humans exert dramatic influences upon the environment, creating novel selective pressures to which organisms must adapt. On the Galapagos, humans have established a permanent presence and have altered selective pressures through influences such as invasive predators and urbanization, affecting iconic species such as Darwin’s finches.2) Here, I ask two key questions: (i) does antipredator behaviour (e.g. FID) change depending on whether invasive predators are historically absent, present, or eradicated? and (ii) to what degree does urbanization affect antipredator behaviour? This study is one of the first to quantify antipredator behaviour in endemic species after the eradication of invasive predators. This will help to understand the consequences of invasive predator eradication and inform conservation measures.3) I quantified flight initiation distance (FID), an antipredator behaviour, in Darwin’s finches, across multiple islands in the Galapagos that varied in the presence, absence, or successful eradication of invasive predators. On islands with human populations, I quantified FID in urban and non-urban populations of finches.4) FID was higher on islands with invasive predators compared to islands with no predators. On islands from which invasive predators were eradicated ∼11 years previously, FID was also higher than on islands with no invasive predators. Within islands that had both urban and non-urban populations of finches, FID was lower in urban finch populations, but only above a threshold human population size. FID in larger urban areas on islands with invasive predators was similar to or lower than FID on islands with no history of invasive predators.5) Overall, these results suggest that invasive predators can have a lasting effect on antipredator behaviour, even after eradication. Furthermore, the effect of urbanization can strongly oppose the effect of invasive predators, reducing antipredator behaviour to levels lower than found on pristine islands with no human influences. These results improve our understanding of human influences on antipredator behaviour which can help inform future conservation and management efforts on islands.

Download Full-text