scholarly journals Mining massive genomic data of two Swiss Braunvieh cattle populations reveals six novel candidate variants that impair reproductive success

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Irene M. Häfliger ◽  
Franz R. Seefried ◽  
Mirjam Spengeler ◽  
Cord Drögemüller
Keyword(s):  
Missense Variant ◽  
Whole Genome Sequencing Data ◽  
Potential Candidate ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Genome Wide ◽  
Early Embryonic Lethality ◽  
A Genome ◽  
Candidate Regions ◽  
Two Populations

Abstract Background This study was carried out on the two Braunvieh populations reared in Switzerland, the dairy Brown Swiss (BS) and the dual-purpose Original Braunvieh (OB). We performed a genome-wide analysis of array data of trios (sire, dam, and offspring) from the routine genomic selection to identify candidate regions showing missing homozygosity and phenotypic associations with five fertility, ten birth, and nine growth-related traits. In addition, genome-wide single SNP regression studies based on 114,890 single nucleotide polymorphisms (SNPs) for each of the two populations were performed. Furthermore, whole-genome sequencing data of 430 cattle including 70 putative haplotype carriers were mined to identify potential candidate variants that were validated by genotyping the current population using a custom array. Results Using a trio-based approach, we identified 38 haplotype regions for BS and five for OB that segregated at low to moderate frequencies. For the BS population, we confirmed two known haplotypes, BH1 and BH2. Twenty-four variants that potentially explained the missing homozygosity and associated traits were detected, in addition to the previously reported TUBD1:p.His210Arg variant associated with BH2. For example, for BS we identified a stop-gain variant (p.Arg57*) in the MRPL55 gene in the haplotype region on chromosome 7. This region is associated with the ‘interval between first and last insemination’ trait in our data, and the MRPL55 gene is known to be associated with early pregnancy loss in mice. In addition, we discuss candidate missense variants in the CPT1C, MARS2, and ACSL5 genes for haplotypes mapped in BS. In OB, we highlight a haplotype region on chromosome 19, which is potentially caused by a frameshift variant (p.Lys828fs) in the LIG3 gene, which is reported to be associated with early embryonic lethality in mice. Furthermore, we propose another potential causal missense variant in the TUBGCP5 gene for a haplotype mapped in OB. Conclusions We describe, for the first time, several haplotype regions that segregate at low to moderate frequencies and provide evidence of causality by trait associations in the two populations of Swiss Braunvieh. We propose a list of six protein-changing variants as potentially causing missing homozygosity. These variants need to be functionally validated and incorporated in the breeding program.

scholarly journals Genome-wide profiling of heritable and de novo STR variations

2016 ◽  
Author(s):  
Thomas Willems ◽  
Dina Zielinski ◽  
Assaf Gordon ◽  
Melissa Gymrek ◽  
Yaniv Erlich
Keyword(s):  
Tandem Repeats ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Genetic Diseases ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Short Tandem

AbstractShort tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases, population genetics applications, and forensic casework. However, STRs have proven problematic to genotype from high-throughput sequencing data. Here, we describe HipSTR, a novel haplotype-based method for robustly genotyping, haplotyping, and phasing STRs from whole genome sequencing data and report a genome-wide analysis and validation of de novo STR mutations.

scholarly journals Investigating the Evolutionary Importance of Denisovan Introgressions in Papua New Guineans and Australians

2015 ◽  
Author(s):  
Ya Hu ◽  
Qiliang Ding ◽  
Yi Wang ◽  
Shuhua Xu ◽  
Yungang He ◽  
...  
Keyword(s):  
False Positive Rate ◽  
Whole Genome Sequencing Data ◽  
Phase Method ◽  
Sequencing Data ◽  
Male Gonad ◽  
Two Phase ◽  
Genome Wide ◽  
A Genome ◽  
Positive Rate ◽  
Olfactory Pit

Previous research reported that Papua New Guineans (PNG) and Australians contain introgressions from Denisovans. Here we present a genome-wide analysis of Denisovan introgressions in PNG and Australians. We firstly developed a two-phase method to detect Denisovan introgressions from whole-genome sequencing data. This method has relatively high detection power (79.74%) and low false positive rate (2.44%) based on simulations. Using this method, we identified 1.34 Gb of Denisovan introgressions from sixteen PNG and four Australian genomes, in which we identified 38,877 Denisovan introgressive alleles (DIAs). We found that 78 Denisovan introgressions were under positive selection. Genes located in the 78 introgressions are related to evolutionarily important functions, such as spermatogenesis, fertilization, cold acclimation, circadian rhythm, development of brain, neural tube, face, and olfactory pit, immunity, etc. We also found that 121 DIAs are missense. Genes harboring the 121 missense DIAs are also related to evolutionarily important functions, such as female pregnancy, development of face, lung, heart, skin, nervous system, and male gonad, visual and smell perception, response to heat, pain, hypoxia, and UV, lipid transport, metabolism, blood coagulation, wound healing, aging, etc. Taken together, this study suggests that Denisovan introgressions in PNG and Australians are evolutionarily important, and may help PNG and Australians in local adaptation. In this study, we also proposed a method that could efficiently identify archaic hominin introgressions in modern non-African genomes.

scholarly journals The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology

2020 ◽  
Author(s):  
Ebrahim Mahmoudi ◽  
Joshua R Atkins ◽  
Yann Quidé ◽  
William R Reay ◽  
Heath M Cairns ◽  
...  
Keyword(s):  
Association Studies ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Brain Morphology ◽  
Whole Genome Sequencing Data ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Genome Wide ◽  
Cortical Morphology

Abstract Genome-wide association studies (GWAS) of schizophrenia have strongly implicated a risk locus in close proximity to the gene for miR-137. While there are candidate single-nucleotide polymorphisms (SNPs) with functional implications for the microRNA’s expression encompassed by the common haplotype tagged by rs1625579, there are likely to be others, such as the variable number tandem repeat (VNTR) variant rs58335419, that have no proxy on the SNP genotyping platforms used in GWAS to date. Using whole-genome sequencing data from schizophrenia patients (n = 299) and healthy controls (n = 131), we observed that the MIR137 4-repeats VNTR (VNTR4) variant was enriched in a cognitive deficit subtype of schizophrenia and associated with altered brain morphology, including thicker left inferior temporal gyrus and deeper right postcentral sulcus. These findings suggest that the MIR137 VNTR4 may impact neuroanatomical development that may, in turn, influence the expression of more severe cognitive symptoms in patients with schizophrenia.

scholarly journals Constructing a Genome-Wide LD Map of WildA. gambiaeUsing Next-Generation Sequencing

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaohong Wang ◽  
Yaw A. Afrane ◽  
Guiyun Yan ◽  
Jun Li
Keyword(s):  
Next Generation Sequencing ◽  
High Throughput Sequencing ◽  
Nucleotide Polymorphisms ◽  
Next Generation ◽  
Sequencing Data ◽  
Chromosome Inversion ◽  
Genome Wide ◽  
A Genome ◽  
Endemic Areas ◽  
Generation Sequencing

Anopheles gambiaeis the major malaria vector in Africa. Examining the molecular basis ofA. gambiaetraits requires knowledge of both genetic variation and genome-wide linkage disequilibrium (LD) map of wildA. gambiaepopulations from malaria-endemic areas. We sequenced the genomes of nine wildA. gambiaemosquitoes individually using next-generation sequencing technologies and detected 2,219,815 common single nucleotide polymorphisms (SNPs), 88% of which are novel. SNPs are not evenly distributed acrossA. gambiaechromosomes. The low SNP-frequency regions overlay heterochromatin and chromosome inversion domains, consistent with the lower recombinant rates at these regions. Nearly one million SNPs that were genotyped correctly in all individual mosquitoes with 99.6% confidence were extracted from these high-throughput sequencing data. Based on these SNP genotypes, we constructed a genome-wide LD map for wildA. gambiaefrom malaria-endemic areas in Kenya and made it available through a public Website. The average size of LD blocks is less than 40 bp, and several large LD blocks were also discovered clustered around theparagene, which is consistent with the effect of insecticide selective sweeps. The SNPs and the LD map will be valuable resources for scientific communities to dissect theA. gambiaegenome.

scholarly journals SVRare: discovering disease-causing structural variants in the 100K Genomes Project

2021 ◽  
Author(s):  
Jing Yu ◽  
Anita Szabo ◽  
Alistair T Pagnamenta ◽  
Ahmed Shalaby ◽  
Edoardo Giacopuzzi ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Kidney Diseases ◽  
Cystic Kidney ◽  
Whole Genome Sequencing Data ◽  
Structural Variants ◽  
Sequencing Data ◽  
Protein Coding ◽  
Genome Wide ◽  
A Genome ◽  
Cystic Kidney Diseases

Discovery of disease-causing structural variants (dcSV) from whole genome sequencing data is difficult due to high number of false positives and a lack of efficient way to estimate allele frequency. Here we introduce SVRare, an application that aggregates structural variants (SV) called by other tools, and efficiently annotates rare SVs to aid dcSVs discovery. Applied in the Genomics England (GEL) research environment to data from the 100K Genomes Project, SVRare aggregated 554,060,126 SVs called by Manta and Canvas in all the 71,408 participants in the rare-disease arm. From a pilot study of 4313 families, SVRare identified 36 novel protein-coding disrupting SVs on diagnostic grade genes that may explain proband's phenotype. It is estimated that SVRare can increase SV-based diagnosis yield by at least 4-fold. We also performed a genome-wide association study, and uncovered clusters of dcSVs in genes with known pathogenicity, such as PKD1/2 - cystic kidney diseases and LDLR - familial hypercholesterolaemia.

scholarly journals Genome-Wide Association Study (GWAS) for Examining the Genomics Controlling Prickle Production in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Archana Khadgi ◽  
Courtney A. Weber
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genomic Region ◽  
Rubus Idaeus ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Red Raspberry ◽  
Genome Wide ◽  
A Genome ◽  
Genotype By Sequencing

Red raspberry (Rubus idaeus L.) is an expanding high-value berry crop worldwide. The presence of prickles, outgrowths of epidermal tissues lacking vasculature, on the canes, petioles, and undersides of leaves complicates both field management and harvest. The utilization of cultivars with fewer prickles or prickle-free canes simplifies production. A previously generated population segregating for prickles utilizing the s locus between the prickle-free cultivar Joan J (ss) and the prickled cultivar Caroline (Ss) was analyzed to identify the genomic region associated with prickle development in red raspberry. Genotype by sequencing (GBS) was combined with a genome-wide association study (GWAS) using fixed and random model circulating probability unification (FarmCPU) to analyze 8474 single nucleotide polymorphisms (SNPs) and identify significant markers associated with the prickle-free trait. A total of four SNPs were identified on chromosome 4 that were associated with the phenotype and were located near or in annotated genes. This study demonstrates how association genetics can be used to decipher the genetic control of important horticultural traits in Rubus, and provides valuable information about the genomic region and potential genes underlying the prickle-free trait.

scholarly journals Genome-Wide Association Analysis of Growth Curve Parameters in Chinese Simmental Beef Cattle

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 192
Author(s):  
Xinghai Duan ◽  
Bingxing An ◽  
Lili Du ◽  
Tianpeng Chang ◽  
Mang Liang ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Candidate Genes ◽  
Growth Curve ◽  
Growth And Development ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Coefficient Of Determination ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome

The objective of the present study was to perform a genome-wide association study (GWAS) for growth curve parameters using nonlinear models that fit original weight–age records. In this study, data from 808 Chinese Simmental beef cattle that were weighed at 0, 6, 12, and 18 months of age were used to fit the growth curve. The Gompertz model showed the highest coefficient of determination (R2 = 0.954). The parameters’ mature body weight (A), time-scale parameter (b), and maturity rate (K) were treated as phenotypes for single-trait GWAS and multi-trait GWAS. In total, 9, 49, and 7 significant SNPs associated with A, b, and K were identified by single-trait GWAS; 22 significant single nucleotide polymorphisms (SNPs) were identified by multi-trait GWAS. Among them, we observed several candidate genes, including PLIN3, KCNS3, TMCO1, PRKAG3, ANGPTL2, IGF-1, SHISA9, and STK3, which were previously reported to associate with growth and development. Further research for these candidate genes may be useful for exploring the full genetic architecture underlying growth and development traits in livestock.

scholarly journals Population Genomics of American Mink Using Whole Genome Sequencing Data

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 258
Author(s):  
Karim Karimi ◽  
Duy Ngoc Do ◽  
Mehdi Sargolzaei ◽  
Younes Miar
Keyword(s):  
Population Genomics ◽  
Association Studies ◽  
American Mink ◽  
Population History ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Sequencing Data ◽  
Effective Population ◽  
Cross Validation Error

Characterizing the genetic structure and population history can facilitate the development of genomic breeding strategies for the American mink. In this study, we used the whole genome sequences of 100 mink from the Canadian Centre for Fur Animal Research (CCFAR) at the Dalhousie Faculty of Agriculture (Truro, NS, Canada) and Millbank Fur Farm (Rockwood, ON, Canada) to investigate their population structure, genetic diversity and linkage disequilibrium (LD) patterns. Analysis of molecular variance (AMOVA) indicated that the variation among color-types was significant (p < 0.001) and accounted for 18% of the total variation. The admixture analysis revealed that assuming three ancestral populations (K = 3) provided the lowest cross-validation error (0.49). The effective population size (Ne) at five generations ago was estimated to be 99 and 50 for CCFAR and Millbank Fur Farm, respectively. The LD patterns revealed that the average r2 reduced to <0.2 at genomic distances of >20 kb and >100 kb in CCFAR and Millbank Fur Farm suggesting that the density of 120,000 and 24,000 single nucleotide polymorphisms (SNP) would provide the adequate accuracy of genomic evaluation in these populations, respectively. These results indicated that accounting for admixture is critical for designing the SNP panels for genotype-phenotype association studies of American mink.

Abstract P359: A Sickle Cell Variant Associates With Urine Albumin Excretion in Genome Wide Association Study of Hispanics: The HCHS/SOL Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Nora Franceschini ◽  
Adrienne Stilp ◽  
Christina L Wassel ◽  
Holly J Mattix-Kramer ◽  
Michael F Flessner ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Sickle Cell ◽  
Missense Variant ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Minority Population ◽  
Genome Wide Association Studies ◽  
Urine Albumin ◽  
Genome Wide ◽  
A Genome

Introduction: Genome wide association studies have identified genetic variants in the Cubillin gene ( CUBN ) that explain inter-individual variation in urine albumin-to-creatinine excretion (UACR) in populations. These studies have not included Hispanics/Latinos, the fast growing minority population in the U.S., who has also high prevalence of chronic kidney disease and its risk factors. Hypothesis: By leveraging on population admixture of Hispanics and using a genome wide association approach, we hypothesized that novel loci associated with UACR would be identified. Methods: We used data from 12,212 self-identified Hispanic individuals recruited in a community-based study, aged 18-74 years at screening (2008-2011), and randomly selected from households in four U.S. field centers (Chicago, IL; Miami, FL; Bronx, NY; San Diego, CA). Urine albumin (mg/dl) and creatinine (g/dl) were measured at the baseline exam. UACR was log-transformed for analysis. Individuals were excluded if reporting to have end-stage renal disease. Genotyping was performed using a custom Illumina Omni2.5M array. Imputation of variants was performed using 1000 Genome Project data from cosmopolitan HapMap samples. After quality control of imputed data, we performed mixed linear regression analyses that accounted for the sampling strategy and family relatedness, for variants with minor allele frequency (MAF) > 0.01 and imputation quality > 0.3. We used additive genetic models and adjusted for age, sex, and principal components which were estimated from the data. In a secondary analysis, we also examine the association of significant variants with kidney function using estimated glomerular filtration rate (eGFR) equations. Results: Among 12,212 participants, 41% were men, and mean age was 46 (SD =13). There was little evidence for genome wide inflation (lambda =1.024). We identified significant associations of single nucleotide polymorphisms (SNPs) with UACR at two loci: CUBN and HBB . The CUBN SNP (chr10:16966414, p=2.1x10-8) is an indel variant with MAF of 0.14, which was not in linkage disequilibrium with previously reported SNP rs1801239 (rsq=0.38, p=1.3x10-4) identified in individuals of European ancestry. The HBB SNP is a missense variant which results in an E [Glu] ⇒ A [Ala] substitution in the beta-globin chain of hemoglobin and a cause of the Mendelian disorder sickle cell anemia (rs334, T allele frequency =0.01, beta=0.44, SE=0.06, p=7.6x10-12). rs344 was not associated with eGFR in our data (p>0.05). Conclusion: This study identified a novel association of a sickle cell missense variant with UACR in Hispanics, and provided evidence for allelic heterogeneity at the CUBN locus. Our findings suggest a role for Mendelian gene variants in increased albuminuria in Hispanic populations with admixture.

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