Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals

The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification.

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Statistical methods for multi-marker testing in genetic association studies

10.37099/mtu.dc.etd-restricted/82 ◽

2012 ◽

Author(s):

Yilin Dai

Keyword(s):

Genetic Association ◽

Statistical Methods ◽

Association Studies ◽

Genetic Association Studies

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Case–Parent Trio Studies in Cleft Lip and Palate

Global Medical Genetics ◽

10.1055/s-0040-1722097 ◽

2020 ◽

Vol 07 (03) ◽

pp. 075-079

Author(s):

Mahamad Irfanulla Khan ◽

Prashanth CS

Keyword(s):

Genetic Variants ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Association Studies ◽

Geographical Location ◽

Genetic Association Studies ◽

Population Based ◽

Genome Wide Association Studies ◽

Family Based ◽

Study Designs

AbstractCleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case–control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case–parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case–parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

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Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection

Scientific Reports ◽

10.1038/s41598-020-79124-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kevin K. Esoh ◽

Tobias O. Apinjoh ◽

Steven G. Nyanjom ◽

Ambroise Wonkam ◽

Emile R. Chimusa ◽

...

Keyword(s):

Genetic Structure ◽

Ethnic Groups ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies ◽

Genomic Region ◽

Sub Saharan Africa ◽

Genome Wide Association Studies ◽

Fine Scale ◽

Sub Saharan

AbstractInferences from genetic association studies rely largely on the definition and description of the underlying populations that highlight their genetic similarities and differences. The clustering of human populations into subgroups (population structure) can significantly confound disease associations. This study investigated the fine-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fine-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi-Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric differentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confirming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fine-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.

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Genomic basis of striking fin shapes and colours in the fighting fish

Molecular Biology and Evolution ◽

10.1093/molbev/msab110 ◽

2021 ◽

Author(s):

Le Wang ◽

Fei Sun ◽

Zi Yi Wan ◽

Baoqing Ye ◽

Yanfei Wen ◽

...

Keyword(s):

Evolutionary Biology ◽

Association Studies ◽

Regulatory Element ◽

Regulatory Elements ◽

Major Effect ◽

Betta Splendens ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Phenotypic Variations ◽

Genomic Basis

Abstract Resolving the genomic basis underlying phenotypic variations is a question of great importance in evolutionary biology. However, understanding how genotypes determine the phenotypes is still challenging. Centuries of artificial selective breeding for beauty and aggression resulted in a plethora of colors, long fin varieties, and hyper-aggressive behavior in the air-breathing Siamese fighting fish (Betta splendens), supplying an excellent system for studying the genomic basis of phenotypic variations. Combining whole genome sequencing, QTL mapping, genome-wide association studies and genome editing, we investigated the genomic basis of huge morphological variation in fins and striking differences in coloration in the fighting fish. Results revealed that the double tail, elephant ear, albino and fin spot mutants each were determined by single major-effect loci. The elephant ear phenotype was likely related to differential expression of a potassium ion channel gene, kcnh8. The albinotic phenotype was likely linked to a cis-regulatory element acting on the mitfa gene and the double tail mutant was suggested to be caused by a deletion in a zic1/zic4 co-enhancer. Our data highlight that major loci and cis-regulatory elements play important roles in bringing about phenotypic innovations and establish Bettas as new powerful model to study the genomic basis of evolved changes.

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A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations

Diagnostics ◽

10.3390/diagnostics11020301 ◽

2021 ◽

Vol 11 (2) ◽

pp. 301

Author(s):

Jana Mrazkova ◽

Petr Sistek ◽

Jan Lochman ◽

Lydie Izakovicova Holla ◽

Zdenek Danek ◽

...

Keyword(s):

Association Studies ◽

Genetic Association Studies ◽

Cost Effective ◽

European Population ◽

Mannose Binding Lectin ◽

Nucleotide Polymorphisms ◽

Online Application ◽

Czech Population ◽

Mannose Binding ◽

Binding Lectin

Mannose-binding lectin (MBL) deficiency caused by the variability in the MBL2 gene is responsible for the susceptibility to and severity of various infectious and autoimmune diseases. A combination of six single nucleotide polymorphisms (SNPs) has a major impact on MBL levels in circulation. The aim of this study is to design and validate a sensitive and economical method for determining MBL2 haplogenotypes. The SNaPshot assay is designed and optimized to genotype six SNPs (rs1800451, rs1800450, rs5030737, rs7095891, rs7096206, rs11003125) and is validated by comparing results with Sanger sequencing. Additionally, an algorithm for online calculation of haplogenotype combinations from the determined genotypes is developed. Three hundred and twenty-eight DNA samples from healthy individuals from the Czech population are genotyped. Minor allele frequencies (MAFs) in the Czech population are in accordance with those present in the European population. The SNaPshot assay for MBL2 genotyping is a high-throughput, cost-effective technique that can be used in further genetic-association studies or in clinical practice. Moreover, a freely available online application for the calculation of haplogenotypes from SNPs is developed within the scope of this project.

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Patterns of linkage disequilibrium atPARK16may explain variances in genetic association studies

Movement Disorders ◽

10.1002/mds.26176 ◽

2015 ◽

Vol 30 (10) ◽

pp. 1335-1342 ◽

Cited By ~ 6

Author(s):

Huihua Li ◽

Yik-Ying Teo ◽

Eng-King Tan

Keyword(s):

Linkage Disequilibrium ◽

Genetic Association ◽

Association Studies ◽

Genetic Association Studies

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Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project

Human Molecular Genetics ◽

10.1093/hmg/ddm205 ◽

2007 ◽

Vol 16 (20) ◽

pp. 2494-2505 ◽

Cited By ~ 23

Author(s):

Yasuhito Nannya ◽

Kenjiro Taura ◽

Mineo Kurokawa ◽

Shigeru Chiba ◽

Seishi Ogawa

Keyword(s):

Genetic Association ◽

Empirical Data ◽

Association Studies ◽

Genetic Association Studies ◽

Hapmap Project ◽

Genome Wide

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Clinical, biochemical and genetic risk factors for 30-day and 5-year mortality in 518 adult patients subjected to cardiopulmonary bypass during cardiac surgery - the INFLACOR study.

Acta Biochimica Polonica ◽

10.18388/abp.2017_2361 ◽

2018 ◽

Vol 65 (2) ◽

pp. 241-250 ◽

Cited By ~ 3

Author(s):

Maciej Michał Kowalik ◽

Romuald Lango ◽

Piotr Siondalski ◽

Magdalena Chmara ◽

Maciej Brzeziński ◽

...

Keyword(s):

Risk Factors ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Genetic Association ◽

Biochemical Parameters ◽

Cox Regression ◽

Association Studies ◽

Nyha Class ◽

Genetic Association Studies ◽

Chronic Obstructive

There is increasing evidence that genetic variability influence patients’ early morbidity after cardiac surgery performed using cardiopulmonary bypass (CPB). The use of mortality as an outcome measure in cardiac surgical genetic association studies is rare. We publish the 30-day and 5-year survival analyses with focus on pre-, intra-, postoperative variables, biochemical parameters, and genetic variants in the INFLACOR (INFlAmmation in Cardiac OpeRations) cohort.In a series of prospectively recruited 518 adult Polish Caucasians who underwent cardiac surgery in which CPB was used, the clinical data, biochemical parameters, IL-6, soluble ICAM-1, TNFa, soluble E-selectin, and 10 single nucleotide polymorphisms were evaluated for their associations with 30-day and 5-year mortality.The 30-day mortality was associated with: pre-operative prothrombin international normalized ratio, intra-operative blood lactate, postoperative serum creatine phosphokinase, and acute kidney injury requiring renal replacement therapy (AKI-RRT) in logistic regression. Factors that determined the 5-year survival included: pre-operative NYHA class, history of peripheral artery disease and severe chronic obstructive pulmonary disease, intra-operative blood transfusion; and postoperative peripheral hypothermia, myocardial infarction, infection, and AKI-RRT in Cox regression. The serum levels of IL-6 and ICAM-1 measured three hours after operation were associated with 30-day and 5-year mortality, respectively. The ICAM1 rs5498 was associated with 30-day and 5-year survival with borderline significance.Different risk factors determined the early (30-day) and late (5-year) survival after adult cardiac surgery in which cardiopulmonary bypass was used. Future genetic association studies in cardiac surgical patients should adjust for the identified chronic and acute postoperative risk factors.

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