scholarly journals Adaptations to new environments in humans: the role of subtle allele frequency shifts

2010 ◽  
Vol 365 (1552) ◽  
pp. 2459-2468 ◽  
Author(s):  
Angela M. Hancock ◽  
Gorka Alkorta-Aranburu ◽  
David B. Witonsky ◽  
Anna Di Rienzo
Keyword(s):  
Phenotypic Diversity ◽  
Human Populations ◽  
Strongly Correlated ◽  
Nucleotide Polymorphisms ◽  
Environmental Correlation ◽  
Single Nucleotide ◽  
Environmental Pressures ◽  
Genome Wide ◽  
Geographically Distributed

Humans show tremendous phenotypic diversity across geographically distributed populations, and much of this diversity undoubtedly results from genetic adaptations to different environmental pressures. The availability of genome-wide genetic variation data from densely sampled populations offers unprecedented opportunities for identifying the loci responsible for these adaptations and for elucidating the genetic architecture of human adaptive traits. Several approaches have been used to detect signals of selection in human populations, and these approaches differ in the assumptions they make about the underlying mode of selection. We contrast the results of approaches based on haplotype structure and differentiation of allele frequencies to those from a method for identifying single nucleotide polymorphisms strongly correlated with environmental variables. Although the first group of approaches tends to detect new beneficial alleles that were driven to high frequencies by selection, the environmental correlation approach has power to identify alleles that experienced small shifts in frequency owing to selection. We suggest that the first group of approaches tends to identify only variants with relatively strong phenotypic effects, whereas the environmental correlation methods can detect variants that make smaller contributions to an adaptive trait.

scholarly journals Type 2 Diabetes (T2D) Associated Polymorphisms Regulate Expression of Adjacent Transcripts in Transformed Lymphocytes, Adipose, and Muscle from Caucasian and African-American Subjects

2011 ◽  
Vol 96 (2) ◽  
pp. E394-E403 ◽  
Author(s):  
Neeraj K. Sharma ◽  
Kurt A. Langberg ◽  
Ashis K. Mondal ◽  
Steven C. Elbein ◽  
Swapan K. Das
Keyword(s):  
Genome Wide Association ◽  
Small Subset ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Allelic Expression Imbalance ◽  
Single Nucleotide ◽  
Metabolic Traits ◽  
Genome Wide

abstract Context: Genome-wide association scans (GWAS) have identified novel single nucleotide polymorphisms (SNPs) that increase T2D susceptibility and indicated the role of nearby genes in T2D pathogenesis. Objective: We hypothesized that T2D-associated SNPs act as cis-regulators of nearby genes in human tissues and that expression of these transcripts may correlate with metabolic traits, including insulin sensitivity (SI). Design, Settings, and Patients: Association of SNPs with the expression of their nearest transcripts was tested in adipose and muscle from 168 healthy individuals who spanned a broad range of SI and body mass index (BMI) and in transformed lymphocytes (TLs). We tested correlations between the expression of these transcripts in adipose and muscle with metabolic traits. Utilizing allelic expression imbalance (AEI) analysis we examined the presence of other cis-regulators for those transcripts in TLs. Results: SNP rs9472138 was significantly (P = 0.037) associated with the expression of VEGFA in TLs while rs6698181 was detected as a cis-regulator for the PKN2 in muscle (P = 0.00027) and adipose (P = 0.018). Significant association was also observed for rs17036101 (P = 0.001) with expression of SYN2 in adipose of Caucasians. Among 19 GWAS-implicated transcripts, expression of VEGFA in adipose was correlated with BMI (r = −0.305) and SI (r = 0.230). Although only a minority of the T2D-associated SNPs were validated as cis-eQTLs for nearby transcripts, AEI analysis indicated presence of other cis-regulatory polymorphisms in 54% of these transcripts. Conclusions: Our study suggests that a small subset of GWAS-identified SNPs may increase T2D susceptibility by modulating expression of nearby transcripts in adipose or muscle.

scholarly journals Population Differentiation at the HLA Genes

2017 ◽  
Author(s):  
Débora Y. C. Brandt ◽  
Jônatas César ◽  
Jérôme Goudet ◽  
Diogo Meyer
Keyword(s):  
Population Differentiation ◽  
Balancing Selection ◽  
Global Scale ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hla Genes ◽  
Genome Wide ◽  
Different Populations ◽  
Genomic Regions

ABSTRACTBalancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by FST. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle this issue, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. However, this result depends on accounting for the differences in allele frequency between selected and putatively neutral sites. Our finding of reduced differentiation at SNPs within HLA genes suggests a predominant role of shared selective pressures among populations at a global scale. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. This pattern was reproduced in simulations of overdominant selection. We conclude that population differentiation at the HLA genes is generally lower than genome-wide, but it may be higher for recently diverged population pairs, and that this pattern can be explained by a simple overdominance regime.

scholarly journals Mining SNPs From EST Databases

1999 ◽  
Vol 9 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Leslie Picoult-Newberg ◽  
Trey E. Ideker ◽  
Mark G. Pohl ◽  
Scott L. Taylor ◽  
Miriam A. Donaldson ◽  
...  
Keyword(s):  
Expressed Sequence Tag ◽  
De Novo ◽  
Cdna Libraries ◽  
Human Populations ◽  
Data Sets ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Using Data

There is considerable interest in the discovery and characterization of single nucleotide polymorphisms (SNPs) to enable the analysis of the potential relationships between human genotype and phenotype. Here we present a strategy that permits the rapid discovery of SNPs from publicly available expressed sequence tag (EST) databases. From a set of ESTs derived from 19 different cDNA libraries, we assembled 300,000 distinct sequences and identified 850 mismatches from contiguous EST data sets (candidate SNP sites), without de novo sequencing. Through a polymerase-mediated, single-base, primer extension technique, Genetic Bit Analysis (GBA), we confirmed the presence of a subset of these candidate SNP sites and have estimated the allele frequencies in three human populations with different ethnic origins. Altogether, our approach provides a basis for rapid and efficient regional and genome-wide SNP discovery using data assembled from sequences from different libraries of cDNAs.[The SNPs identified in this study can be found in the National Center of Biotechnology (NCBI) SNP database under submitter handles ORCHID (SNPS-981210-A) and debnick (SNPS-981209-A and SNPS-981209-B).]

scholarly journals Association Between rs12037447, rs146732504, rs151078858, rs55723436, and rs6094136 Polymorphisms and Kawasaki Disease in the Population of Polish Children

2021 ◽  
Vol 9 ◽  
Author(s):  
Piotr Buda ◽  
Maciej Chyb ◽  
Anna Smorczewska-Kiljan ◽  
Anna Wieteska-Klimczak ◽  
Agata Paczesna ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Developed Countries ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Coronary Artery Involvement ◽  
Genome Wide

Background: Kawasaki disease (KD) is an acute self-limited febrile vasculitis that mainly affects young children. Coronary artery involvement is the most serious complication in children with KD. It is currently the leading cause of acquired cardiac disease in children from developed countries. Literature data indicate a significant role of genetic susceptibility to KD.Objective: The aim of this study was to perform the first Genome-Wide Association Study (GWAS) in a population of Polish children with KD and identify susceptible genes involved in the pathogenesis of KD.Materials and Methods: The blood samples of Kawasaki disease patients (n = 119) were collected between 2016 and 2020, isolated and stored at the Department of Pediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute in Warsaw. The control group was based on Polish donors (n = 6,071) registered as the POPULOUS collection at the Biobank Lab of The Department of Molecular Biophysics in University of Lodz. DNA samples were genotyped for 558,231 Single Nucleotide Polymorphisms (SNPs) using the 24 × 1 Infinium HTS Human Core Exome microarrays according to the protocol provided by the manufacturer. In order to discover and verify genetic risk-factors for KD, association analysis was carried out using PLINK 1.9.Results: Of all 164,395 variants, 5 were shown to occur statistically (padjusted < 0.05) more frequent in Kawasaki disease patients than in controls. Those are: rs12037447 in non-coding sequence (padjusted = 8.329 × 10−4, OR = 8.697, 95% CI; 3.629–20.84) and rs146732504 in KIF25 (padjusted = 0.007354, OR = 11.42, 95% CI; 3.79–34.43), rs151078858 in PTPRJ (padjusted = 0.04513, OR = 8.116, 95% CI; 3.134–21.01), rs55723436 in SPECC1L (padjusted = 0.04596, OR = 5.596, 95% CI; 2.669–11.74), rs6094136 in RPN2 (padjusted = 0.04755, OR = 10.08, 95% CI; 3.385–30.01) genes.Conclusion: Polymorphisms of genes KIF25, PTRPJ, SPECC1L, RNP2 may be linked with the incidence of Kawasaki disease in Polish children.

scholarly journals Analysis of coding variants in the human FTO gene from the gnomAD database

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0248610
Author(s):  
Mauro Lúcio Ferreira Souza Junior ◽  
Jaime Viana de Sousa ◽  
João Farias Guerreiro
Keyword(s):  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Studies ◽  
Rare Mutations ◽  
Functional Variants ◽  
Pathogenicity Prediction ◽  
Complete Sequencing ◽  
Coding Variants

Single nucleotide polymorphisms (SNPs) in the first intron of the FTO gene reported in 2007 continue to be the known variants with the greatest effect on adiposity in different human populations. Coding variants in the FTO gene, on the other hand, have been little explored, although data from complete sequencing of the exomes of various populations are available in public databases and provide an excellent opportunity to investigate potential functional variants in FTO. In this context, this study aimed to track nonsynonymous variants in the exons of the FTO gene in different population groups employing the gnomAD database and analyze the potential functional impact of these variants on the FTO protein using five publicly available pathogenicity prediction programs. The findings revealed 345 rare mutations, of which 321 are missense (93%), 19 are stop gained (5.6%) and five mutations are located in the splice region (1.4%). Of these, 134 (38.8%) were classified as pathogenic, 144 (41.7%) as benign and 67 (19.5%) as unknown. The available data, however, suggest that these variants are probably not associated with BMI and obesity, but instead, with other diseases. Functional studies are, therefore, required to identify the role of these variants in disease genesis.

scholarly journals Novel roles of DNA variation in maintenance of AT rich genome and conserved function in rats

2021 ◽  
Author(s):  
Amy Zinski ◽  
Weimin Wang ◽  
Jennifer Michal ◽  
Leah Solberg Woods ◽  
Ryan McLaughlin ◽  
...  
Keyword(s):  
Genome Stability ◽  
Gc Content ◽  
Untranslated Regions ◽  
Strongly Correlated ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Dna Variation ◽  
Functional Conservation ◽  
Genome Wide ◽  
Genome Content

Abstract Whether or not DNA variation changes genome-wide nucleotide compositions remains largely unknown. By examining 4,604,291 DNA variants between two rat strains, we observed that sequencing depth is strongly correlated with genome content as 21.41, 38.36, 44.26 and 6512.70 average reads per locus were collected for Y, X, autosomes and mitochondrial (MT) genomes; respectively (P<0.0001). The mutation rates corresponding to these four genome subsets were 0.055, 0.401, 1.733 and 4.475 variants per kb (P<0.0001), confirming the links between recombination frequencies and DNA variability. Although SNPs (single nucleotide polymorphisms) tend to reduce AT content, more CG deletions than CG insertions (INDELs) implies the GC content would not increase. Therefore, the SNP-INDEL interplay may play a key role in maintenance of the AT-rich genomes in rat during evolution. Formation of CpG sites appear to be hindered because genome-wide G INDELs (1.38%) with C as the 5’-nucleotide and CG INDELs (1.19%) are rare. However, the relatively high C—>G/G—>C rate in 5’UTRs (untranslated regions) and G/C INDELs in the 5’UTR and/or exonic regions highlight their importance for execution of gene function. Our study provides evidence that DNA variation does not jeopardize genome stability and functional conservation during evolution.

scholarly journals The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update

2021 ◽  
Vol 22 (13) ◽  
pp. 6678
Author(s):  
Robert Eckenstaler ◽  
Ralf A. Benndorf
Keyword(s):  
Early Onset ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Functional Analyses ◽  
Urate Reabsorption ◽  
Shed Light

Urate homeostasis in humans is a complex and highly heritable process that involves i.e., metabolic urate biosynthesis, renal urate reabsorption, as well as renal and extrarenal urate excretion. Importantly, disturbances in urate excretion are a common cause of hyperuricemia and gout. The majority of urate is eliminated by glomerular filtration in the kidney followed by an, as yet, not fully elucidated interplay of multiple transporters involved in the reabsorption or excretion of urate in the succeeding segments of the nephron. In this context, genome-wide association studies and subsequent functional analyses have identified the ATP-binding cassette (ABC) transporter ABCG2 as an important urate transporter and have highlighted the role of single nucleotide polymorphisms (SNPs) in the pathogenesis of reduced cellular urate efflux, hyperuricemia, and early-onset gout. Recent publications also suggest that ABCG2 is particularly involved in intestinal urate elimination and thus may represent an interesting new target for pharmacotherapeutic intervention in hyperuricemia and gout. In this review, we specifically address the involvement of ABCG2 in renal and extrarenal urate elimination. In addition, we will shed light on newly identified polymorphisms in ABCG2 associated with early-onset gout.

The current review of adolescent obesity: the role of genetic factors

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Birsen Yılmaz ◽  
Makbule Gezmen Karadağ
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Heterogeneous Condition ◽  
Current Review ◽  
Genome Wide

AbstractObesity, a complex, multi-factor and heterogeneous condition, is thought to result from the interaction of environmental and genetic factors. Considering the result of adolescence obesity in adulthood, the role of genetic factors comes to the fore. Recently, many genome-wide association studies (GWAS) have been conducted and many loci associated with adiposity have been identified. In adolescents, the strongest association with obesity has been found in single nucleotide polymorphisms (SNP) in the FTO gene. Besides FTO, GWAS showed consistent effects between variants in MC4R, TMEM18, TNNI3K, SEC16B, GNPDA2, POMC and obesity. However, these variants may not have similar effects for all ethnic groups. Although recently genetic factors are considered to contribute to obesity, relatively little is known about the specific loci related to obesity and the mechanisms by which they cause obesity.

scholarly journals Genetics and Epigenetics in Allergic Rhinitis

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2004
Author(s):  
Bo Yoon Choi ◽  
Munsoo Han ◽  
Ji Won Kwak ◽  
Tae Hoon Kim
Keyword(s):  
Allergic Rhinitis ◽  
Association Studies ◽  
Large Population ◽  
Allergic Diseases ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Advanced Technique ◽  
Single Nucleotide ◽  
Genome Wide

The pathogenesis of allergic rhinitis is associated with genetic, environmental, and epigenetic factors. Genotyping of single nucleotide polymorphisms (SNPs) is an advanced technique in the field of molecular genetics that is closely correlated with genome-wide association studies (GWASs) in large population groups with allergic diseases. Many recent studies have paid attention to the role of epigenetics, including alteration of DNA methylation, histone acetylation, and miRNA levels in the pathogenesis of allergic rhinitis. In this review article, genetics and epigenetics of allergic rhinitis, including information regarding functions and significance of previously known and newly-discovered genes, are summarized. Directions for future genetic and epigenetic studies of allergic rhinitis are also proposed.

Sign in / Sign up

Export Citation Format

Share Document