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Trends in Ecology & Evolution Mar 2020The particular combinations of alleles that define haplotypes along individual chromosomes can be determined with increasing ease and accuracy by using current... (Review)
Review
The particular combinations of alleles that define haplotypes along individual chromosomes can be determined with increasing ease and accuracy by using current sequencing technologies. Beyond allele frequencies, haplotype data collected in population samples contain information about the history of allelic associations in gene genealogies, and this is of tremendous potential for conservation genomics. We provide an overview of how haplotype information can be used to assess historical demography, gene flow, selection, and the evolutionary outcomes of hybridization across different timescales relevant to conservation issues. We address technical aspects of applying such approaches to nonmodel species. We conclude that there is much to be gained by integrating haplotype-based analyses in future conservation genomics studies.
Topics: Alleles; Gene Flow; Gene Frequency; Genomics; Haplotypes
PubMed: 31810774
DOI: 10.1016/j.tree.2019.10.012 -
Cell Mar 2019Recent developments in genetics and genomics are providing a detailed and systematic characterization of the genetic underpinnings of common metabolic diseases and... (Review)
Review
Recent developments in genetics and genomics are providing a detailed and systematic characterization of the genetic underpinnings of common metabolic diseases and traits, highlighting the inherent complexity within systems for homeostatic control and the many ways in which that control can fail. The genetic architecture underlying these common metabolic phenotypes is complex, with each trait influenced by hundreds of loci spanning a range of allele frequencies and effect sizes. Here, we review the growing appreciation of this complexity and how this has fostered the implementation of genome-scale approaches that deliver robust mechanistic inference and unveil new strategies for translational exploitation.
Topics: Alleles; Chromosome Mapping; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Metabolic Diseases; Phenotype; Quantitative Trait Loci
PubMed: 30901536
DOI: 10.1016/j.cell.2019.02.024 -
Fa Yi Xue Za Zhi Oct 2021
Topics: Alleles; Gene Frequency; Genotype
PubMed: 35191256
DOI: 10.12116/j.issn.1004-5619.2020.500402 -
Heredity Oct 2016Effective population size (Ne) is a key parameter in population genetics. It has important applications in evolutionary biology, conservation genetics and plant and... (Review)
Review
Effective population size (Ne) is a key parameter in population genetics. It has important applications in evolutionary biology, conservation genetics and plant and animal breeding, because it measures the rates of genetic drift and inbreeding and affects the efficacy of systematic evolutionary forces, such as mutation, selection and migration. We review the developments in predictive equations and estimation methodologies of effective size. In the prediction part, we focus on the equations for populations with different modes of reproduction, for populations under selection for unlinked or linked loci and for the specific applications to conservation genetics. In the estimation part, we focus on methods developed for estimating the current or recent effective size from molecular marker or sequence data. We discuss some underdeveloped areas in predicting and estimating Ne for future research.
Topics: Biological Evolution; Gene Frequency; Genetic Drift; Genetic Linkage; Genetic Markers; Genetics, Population; Inbreeding; Linkage Disequilibrium; Models, Genetic; Mutation; Population Density; Reproduction; Selection, Genetic
PubMed: 27353047
DOI: 10.1038/hdy.2016.43 -
Cell Cycle (Georgetown, Tex.) Jan 2022To explore the relationship between fut3 gene polymorphism and colonic polyps.
OBJECTIVE
To explore the relationship between fut3 gene polymorphism and colonic polyps.
METHODS
Two hundred patients with colonic polyps and 200 healthy people in our hospital in recent 3 years were taken as the research objects, as the disease group and the control group, respectively. The disease group was divided into cancerous colonic polyps group (n = 50) and non-cancerous colonic polyps group (n = 150). The peripheral blood nucleated cells of the subjects were collected and isolated. The fut3 gene polymorphism was obtained by sequencing and analyzed combined with the expression of fut3 gene and the level of tumor markers.
RESULTS
The frequency of allele C at rs2561796 locus in the disease group was significantly higher than that in the control group ( < 0.05). The frequency of Ag genotype at rs441158 locus in the disease group was significantly higher than that in the control group, and the frequency of Ca genotype at rs2561796 locus was significantly lower than that in the control group ( < 0.05). In the disease group, the frequency of AA + Ag in the dominant model at rs441158 was significantly higher than that in the control group, and the frequency of Ca + AA in the invisible model at rs2561796 was significantly higher than that in the control group ( < 0.05). The frequency of CGC haplotype in the disease group was higher than that in the control group ( < 0.05). The linkage disequilibrium of rs441158 and rs2561796 loci of fut3 gene was high (' = 0.423). The genotype of rs372725 of fut3 gene was correlated with the expression of fut3 gene ( < 0.05). The expression of fut3 gene in patients with CC genotype was significantly higher than that in patients with other genotypes ( < 0.05). Conclusion: fut3 gene polymorphism is associated with the susceptibility and carcinogenesis of colonic polyps.
Topics: Alleles; Colon; Colonic Polyps; Fucosyltransferases; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Polymorphism, Single Nucleotide
PubMed: 34936845
DOI: 10.1080/15384101.2021.2012036 -
Current Biology : CB Oct 2011
Review
Topics: Biological Evolution; Gene Frequency; Genetic Drift; Genetics, Population; Humans; Mutation; Population Density; Selection, Genetic
PubMed: 22032182
DOI: 10.1016/j.cub.2011.08.007 -
Cells Sep 2022Natural Killer (NK) cells are innate immune cells that mediate antiviral and antitumor responses. NK cell activation and induction of effector functions are tightly...
Natural Killer (NK) cells are innate immune cells that mediate antiviral and antitumor responses. NK cell activation and induction of effector functions are tightly regulated by the integration of activating and inhibitory receptors such as killer immunoglobulin-like receptors (KIR). genes are characterized by a high degree of diversity due to presence or absence, gene copy number and allelic polymorphism. The aim of this study was to establish the distribution of genes and genotypes, to infer the most common haplotypes in an admixed Colombian population and to compare these gene frequencies with some Central and South American populations and worldwide. A total of 161 individuals from Medellin, Colombia were included in the study. Genomic DNA was used for and genotyping. We analyzed only gene-content (presence or absence) based on PCR-SSO. The genotype, most common haplotypes and combinations of and ligands frequencies were estimated according to the presence or absence of and genes. Dendrograms, principal component (PC) analysis and Heatmap analysis based on genetic distance were constructed to compare gene frequencies among Central and South American, worldwide and Amerindian populations. The 16 genes analyzed were distributed in 37 different genotypes and the 7 most frequent inferred haplotypes. Importantly, we found three new genotypes not previously reported in any other ethnic group. Our genetic distance, PC and Heatmap analysis revealed marked differences in the distribution of gene frequencies in the Medellin population compared to worldwide populations. These differences occurred mainly in the activating isoforms, which are more frequent in our population, particularly . Finally, we observed unique structural patterns of genotypes, which evidences the potential diversity and variability of this gene family in our population, and the need for exhaustive genetic studies to expand our understanding of the gene complex in Colombian populations.
Topics: Antiviral Agents; Gene Frequency; Humans; Immunoglobulins; Receptors, KIR; South America
PubMed: 36139351
DOI: 10.3390/cells11182776 -
Nature Genetics Oct 2022Several biobanks, including UK Biobank (UKBB), are generating large-scale sequencing data. An existing method, SAIGE-GENE, performs well when testing variants with minor...
Several biobanks, including UK Biobank (UKBB), are generating large-scale sequencing data. An existing method, SAIGE-GENE, performs well when testing variants with minor allele frequency (MAF) ≤ 1%, but inflation is observed in variance component set-based tests when restricting to variants with MAF ≤ 0.1% or 0.01%. Here, we propose SAIGE-GENE+ with greatly improved type I error control and computational efficiency to facilitate rare variant tests in large-scale data. We further show that incorporating multiple MAF cutoffs and functional annotations can improve power and thus uncover new gene-phenotype associations. In the analysis of UKBB whole exome sequencing data for 30 quantitative and 141 binary traits, SAIGE-GENE+ identified 551 gene-phenotype associations.
Topics: Gene Frequency; Genome-Wide Association Study; Phenotype; Exome Sequencing
PubMed: 36138231
DOI: 10.1038/s41588-022-01178-w -
Nature Genetics May 2019In numerous applications, from working with animal models to mapping the genetic basis of human disease susceptibility, knowing whether a single disrupting mutation in a... (Review)
Review
In numerous applications, from working with animal models to mapping the genetic basis of human disease susceptibility, knowing whether a single disrupting mutation in a gene is likely to be deleterious is useful. With this goal in mind, a number of measures have been developed to identify genes in which protein-truncating variants (PTVs), or other types of mutations, are absent or kept at very low frequency in large population samples-genes that appear 'intolerant' to mutation. One measure in particular, the probability of being loss-of-function intolerant (pLI), has been widely adopted. This measure was designed to classify genes into three categories, null, recessive and haploinsufficient, on the basis of the contrast between observed and expected numbers of PTVs. Such population-genetic approaches can be useful in many applications. As we clarify, however, they reflect the strength of selection acting on heterozygotes and not dominance or haploinsufficiency.
Topics: Animals; Gene Frequency; Genes, Recessive; Genetic Drift; Genetics, Population; Haploinsufficiency; Heterozygote; Humans; Loss of Function Mutation; Models, Genetic; Mutation; Selection, Genetic
PubMed: 30962618
DOI: 10.1038/s41588-019-0383-1 -
Cell Mar 2019Identifying the causes of similarities and differences in genetic disease prevalence among humans is central to understanding disease etiology. While present-day humans... (Review)
Review
Identifying the causes of similarities and differences in genetic disease prevalence among humans is central to understanding disease etiology. While present-day humans are not strongly differentiated, vast amounts of genomic data now make it possible to study subtle patterns of genetic variation. This allows us to trace our genomic history thousands of years into the past and its implications for the distribution of disease-associated variants today. Genomic analyses have shown that demographic processes shaped the distribution and frequency of disease-associated variants over time. Furthermore, local adaptation to new environmental conditions-including pathogens-has generated strong patterns of differentiation at particular loci. Researchers are also beginning to uncover the genetic architecture of complex diseases, affected by many variants of small effect. The field of population genomics thus holds great potential for providing further insights into the evolution of human disease.
Topics: Adaptation, Physiological; Alleles; Evolution, Molecular; Gene Frequency; Genetic Diseases, Inborn; Genetic Drift; Genetic Variation; Genetics, Population; Genomics; Humans; Metagenomics; Models, Genetic; Phylogeny
PubMed: 30901534
DOI: 10.1016/j.cell.2019.01.052