scholarly journals Parent-offspring inference in highly inbred populations

2021 ◽  
Author(s):  
Jan-Niklas Runge ◽  
Barbara König ◽  
Anna K. Lindholm ◽  
Andres Bendesky
Keyword(s):  
Genetic Similarity ◽  
Genetic Differences ◽  
New Method ◽  
Genotyping Errors ◽  
Genetic Studies ◽  
First Degree Relatives ◽  
Genome Wide ◽  
Experimental Populations ◽  
Inference Methods ◽  
Inbred Populations

Genealogical relationships are fundamental components of genetic studies. However, it is often challenging to infer correct and complete pedigrees even when genome-wide information is available. For example, inbreeding can obfuscate genetic differences between individuals, making it difficult to even distinguish first-degree relatives such as parent-offspring from full siblings. Similarly, genotyping errors can interfere with the detection of genetic similarity between parents and their offspring. Inbreeding is common in natural, domesticated, and experimental populations and genotyping of these populations often has more errors than in human datasets, so efficient methods for building pedigrees under these conditions are necessary. Here, we present a new method for parent-offspring inference in inbred pedigrees called SPORE (Specific Parent-Offspring Relationship Estimation). SPORE is vastly superior to existing pedigree-inference methods at detecting parent-offspring relationships, in particular when inbreeding is high or in the presence of genotyping errors, or both. SPORE therefore fills an important void in the arsenal of pedigree inference tools.

A new method for quantifying genotyping errors for noninvasive genetic studies

2009 ◽  
Vol 11 (4) ◽  
pp. 1567-1571 ◽  
Author(s):  
Xiangjiang Zhan ◽  
Xiudeng Zheng ◽  
Michael W. Bruford ◽  
Fuwen Wei ◽  
Yi Tao
Keyword(s):  
New Method ◽  
Genotyping Errors ◽  
Genetic Studies

scholarly journals Detecting Genetic Associations betweenATG5and Lupus Nephritis bytrans-eQTL

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yue-miao Zhang ◽  
Fa-juan Cheng ◽  
Xu-jie Zhou ◽  
Yuan-yuan Qi ◽  
Ping Hou ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Information ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Genome Wide ◽  
Custom Made ◽  
Regulatory Effects

Objectives. Numerous loci were identified to perturb gene expression intrans. As elevatedATG5expression was observed in systemic lupus erythematosus (SLE), the study was conducted to analyze the genome-wide genetic regulatory mechanisms associated withATG5expression in a Chinese population with lupus nephritis (LN).Methods. The online expression quantitative trait loci database was searched fortrans-expression single nucleotide polymorphisms (trans-eSNPs) ofATG5. Taggingtrans-eSNPs were genotyped by a custom-made genotyping chip in 280 patients and 199 controls. For positive findings, clinical information and bioinformation analyses were performed.Results. Fourtrans-eSNPs were observed to be associated with susceptibility to LN (P< 0.05), including ANKRD50 rs17008504, AGA rs2271100, PAK7 rs6056923, and TET2 rs1391441, while seven othertrans-eSNPs showed marginal significant associations (0.05 <P< 0.1). Correlations between thetrans-eSNPs andATG5expression and different expression levels ofATG5in SLE patients and controls were validated, and their regulatory effects were annotated. However, no significant associations were observed between different genotypes oftrans-eSNPs and severity or outcome of the patients.Conclusion. Using the new systemic genetics approach, we identified 10 loci associated with susceptibility to LN potentially, which may be complementary to future pathway based genetic studies.

scholarly journals Genome-wide non-HLA donor-recipient genetic differences influence renal allograft survival via early allograft fibrosis

2020 ◽  
Vol 98 (3) ◽  
pp. 758-768
Author(s):  
Zhongyang Zhang ◽  
Madhav C. Menon ◽  
Weijia Zhang ◽  
Eli Stahl ◽  
Bao-Li Loza ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Genetic Differences ◽  
Allograft Survival ◽  
Genome Wide

scholarly journals Partitioning heritability by functional category using GWAS summary statistics

2015 ◽  
Author(s):  
Hilary Kiyo Finucane ◽  
Brendan Bulik-Sullivan ◽  
Alexander Gusev ◽  
Gosia Trynka ◽  
Yakir Reshef ◽  
...  
Keyword(s):  
Association Studies ◽  
Smoking Behavior ◽  
Complex Diseases ◽  
New Method ◽  
Age At Menarche ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Cell Type ◽  
Genome Wide ◽  
Cell Type Specific

Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here, we analyze a broad set of functional elements, including cell-type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits spanning a total of 1.3 million phenotype measurements. To enable this analysis, we introduce a new method for partitioning heritability from GWAS summary statistics while controlling for linked markers. This new method is computationally tractable at very large sample sizes, and leverages genome-wide information. Our results include a large enrichment of heritability in conserved regions across many traits; a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers; and many cell-type-specific enrichments including significant enrichment of central nervous system cell types in body mass index, age at menarche, educational attainment, and smoking behavior. These results demonstrate that GWAS can aid in understanding the biological basis of disease and provide direction for functional follow-up.

scholarly journals Molecular neuroanatomy of anorexia nervosa

2018 ◽  
Author(s):  
Derek Howard ◽  
Priscilla Negraes ◽  
Aristotle N. Voineskos ◽  
Allan S. Kaplan ◽  
Alysson Muotri ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Fetal Brain ◽  
Marker Genes ◽  
Genetic Studies ◽  
Gene Sets ◽  
Genome Wide ◽  
Calcitonin Gene ◽  
Ventral Tegmental ◽  
Deep Brain ◽  
Cell Study

AbstractAnorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using unbiased genome-wide methods, recent studies have associated a variety of genes with the disorder. We characterized these genes by projecting them into aggregated gene expression data from reference transcriptomic atlases of the prenatal and adult human brain. We found that genes from an induced stem cell study of anorexia nervosa are expressed at higher levels in the lateral parabrachial and the ventral tegmental areas. The adult expression enrichment of the lateral parabrachial is confirmed with genes from two independent genetic studies. In the fetal brain, enrichment of the ventral tegmental area is also observed for the six genes near the only common variant associated with the disorder (rs4622308). We also observed signals in the adult and fetal pontine raphe, but they were not observed when using the genes from the genetic studies. In addition to signals related to calcitonin gene-related peptide neurons and the tachykinin, we found more than the expected number of microglia marker genes within the gene sets. Using mouse transcriptomic data, we identified several anorexia nervosa associated genes that are differentially expressed during food deprivation. While these genes that respond to fasting are not enriched in the gene sets, we highlightRPS26which is proximal to rs4622308. We did not observe expression enrichment in the cingulate cortex or hypothalamus suggesting other targets for deep brain stimulation should be considered for severe cases. This work improves our understanding of the neurobiological causes of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.

4. What are the contributions of environments and genes to intelligence differences?

2020 ◽  
pp. 50-69
Author(s):  
Ian J. Deary
Keyword(s):  
Association Studies ◽  
Twin Studies ◽  
Identical Twins ◽  
New Method ◽  
Genome Wide Association ◽  
Shared Environment ◽  
Genome Wide Association Studies ◽  
Genetic Inheritance ◽  
Genome Wide ◽  
Shared Environments

‘What are the contributions of environments and genes to intelligence differences?’ asks whether genetic inheritance and the environments people experience affect intelligence differences. Researchers use two main resources to answer this question: twins and samples of DNA. Studies of identical and non-identical twins are used to show the contributions of genes, shared environment, and non-shared environment to people’s differences in traits. Twin studies tell us that by adulthood, about two-thirds of intelligence differences are caused by how people vary in their genetic inheritance, and that both shared and non-shared environments make significant contributions to intelligence differences. The introduction of genome-wide association studies in 2011 has provided a new method of estimating the heritability of intelligence.

scholarly journals A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model

Genetics ◽  
2019 ◽  
Vol 214 (3) ◽  
pp. 691-702
Author(s):  
Anika C. Bissahoyo ◽  
Yuying Xie ◽  
Lynda Yang ◽  
R. Scott Pearsall ◽  
Daekee Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Genetic Architecture ◽  
Inbred Strains ◽  
Genome Wide Association ◽  
Polygenic Resistance ◽  
Genetic Studies ◽  
Polygenic Model ◽  
Genome Wide ◽  
Dominant Characteristic

The azoxymethane model of colorectal cancer (CRC) was used to gain insights into the genetic heterogeneity of nonfamilial CRC. We observed significant differences in susceptibility parameters across 40 mouse inbred strains, with 6 new and 18 of 24 previously identified mouse CRC modifier alleles detected using genome-wide association analysis. Tumor incidence varied in F1 as well as intercrosses and backcrosses between resistant and susceptible strains. Analysis of inheritance patterns indicates that resistance to CRC development is inherited as a dominant characteristic genome-wide, and that susceptibility appears to occur in individuals lacking a large-effect, or sufficient numbers of small-effect, polygenic resistance alleles. Our results suggest a new polygenic model for inheritance of nonfamilial CRC, and that genetic studies in humans aimed at identifying individuals with elevated susceptibility should be pursued through the lens of absence of dominant resistance alleles rather than for the presence of susceptibility alleles.

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