scholarly journals PRICKLE1 × FOCAD Interaction Revealed by Genome-Wide vQTL Analysis of Human Facial Traits

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongjing Liu ◽  
Hyo-Jeong Ban ◽  
Ahmed M. El Sergani ◽  
Myoung Keun Lee ◽  
Jacqueline T. Hecht ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Strong Support ◽  
Variable Structure ◽  
Cranial Base ◽  
Facial Morphology ◽  
Genome Wide ◽  
A Genome ◽  
Trait Variance ◽  
Mean Size ◽  
The Mean

The human face is a highly complex and variable structure resulting from the intricate coordination of numerous genetic and non-genetic factors. Hundreds of genomic loci impacting quantitative facial features have been identified. While these associations have been shown to influence morphology by altering the mean size and shape of facial measures, their effect on trait variance remains unclear. We conducted a genome-wide association analysis for the variance of 20 quantitative facial measurements in 2,447 European individuals and identified several suggestive variance quantitative trait loci (vQTLs). These vQTLs guided us to conduct an efficient search for gene-by-gene (G × G) interactions, which uncovered an interaction between PRICKLE1 and FOCAD affecting cranial base width. We replicated this G × G interaction signal at the locus level in an additional 5,128 Korean individuals. We used the hypomorphic Prickle1Beetlejuice (Prickle1Bj) mouse line to directly test the function of Prickle1 on the cranial base and observed wider cranial bases in Prickle1Bj/Bj. Importantly, we observed that the Prickle1 and Focadhesin proteins co-localize in murine cranial base chondrocytes, and this co-localization is abnormal in the Prickle1Bj/Bj mutants. Taken together, our findings uncovered a novel G × G interaction effect in humans with strong support from both epidemiological and molecular studies. These results highlight the potential of studying measures of phenotypic variability in gene mapping studies of facial morphology.

Genome-wide association analysis of resistance to Pseudoperonospora cubensis in citron watermelon

Plant Disease ◽  
2021 ◽  
Author(s):  
Dennis Katuuramu ◽  
Sandra Branham ◽  
Amnon Levi ◽  
Patrick Wechter
Keyword(s):  
Candidate Genes ◽  
Genome Wide Association Study ◽  
Citrullus Lanatus ◽  
Phenotypic Variability ◽  
Germplasm Collection ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Pseudoperonospora Cubensis ◽  
Genome Wide ◽  
A Genome

Cultivated sweet watermelon (Citrullus lanatus) is an important vegetable crop for millions of people around the world. There are limited sources of resistance to economically important diseases within C. lanatus, whereas Citrullus amarus has a reservoir of traits that can be exploited to improve C. lanatus for resistance to biotic and abiotic stresses. Cucurbit downy mildew (CDM), caused by Pseudoperonospora cubensis, is an emerging threat to watermelon production. We screened 122 C. amarus accessions for resistance to CDM over two tests (environments). The accessions were genotyped by whole-genome resequencing to generate 2,126,759 single nucleotide polymorphic (SNP) markers. A genome-wide association study was deployed to uncover marker-trait associations and identify candidate genes underlying resistance to CDM. Our results indicate the presence of wide phenotypic variability (1.1 - 57.8%) for leaf area infection, representing a 50.7-fold variation for CDM resistance across the C. amarus germplasm collection. Broad-sense heritability estimate was 0.55, implying the presence of moderate genetic effects for resistance to CDM. The peak SNP markers associated with resistance to P. cubensis were located on chromosomes Ca03, Ca05, Ca07, and Ca11. The significant SNP markers accounted for up to 30% of the phenotypic variation and were associated with promising candidate genes encoding disease resistance proteins, leucine-rich repeat receptor-like protein kinase, and WRKY transcription factor. This information will be useful in understanding the genetic architecture of the P. cubensis-Citrullus spp. patho-system as well as development of resources for genomics-assisted breeding for resistance to CDM in watermelon.

scholarly journals Ancestral contributions to contemporary European complex traits

2021 ◽  
Author(s):  
Davide Marnetto ◽  
Vasili Pankratov ◽  
Mayukh Mondal ◽  
Francesco Montinaro ◽  
Katri Pärna ◽  
...  
Keyword(s):  
Bronze Age ◽  
Complex Traits ◽  
Phenotypic Variability ◽  
Complex Trait ◽  
Blood Cholesterol ◽  
Hunter Gatherers ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

The contemporary European genetic makeup formed in the last 8000 years as the combination of three main genetic components: the local Western Hunter-Gatherers, the incoming Neolithic Farmers from Anatolia and the Bronze Age component from the Pontic Steppes. When meeting into the post-Neolithic European environment, the genetic variants accumulated during their three distinct evolutionary histories mixed and came into contact with new environmental challenges. Here we investigate how this genetic legacy reflects on the complex trait landscape of contemporary European populations, using the Estonian Biobank as a case study. For the first time we directly connect the phenotypic information available from biobank samples with the genetic similarity to these ancestral groups, both at a genome-wide level and focusing on genomic regions associated with each of the 27 complex traits we investigated. We also found SNPs connected to pigmentation, cholesterol, sleep, diastolic blood pressure, and body mass index (BMI) to show signals of selection following the post Neolithic admixture events. We recapitulate existing knowledge about pigmentation traits, corroborate the connection between Steppe ancestry and height and highlight novel associations. Among others, we report the contribution of Hunter Gatherer ancestry towards high BMI and low blood cholesterol levels. Our results show that the ancient components that form the contemporary European genome were differentiated enough to contribute ancestry-specific signatures to the phenotypic variability displayed by contemporary individuals in at least 11 out of 27 of the complex traits investigated here.

scholarly journals Genome-Wide Association Study Reveals Genetic Architecture of Septoria Tritici Blotch Resistance in a Historic Landrace Collection

2021 ◽  
Author(s):  
Anik Dutta ◽  
Daniel Croll ◽  
Bruce A. McDonald ◽  
Simon G. Krattinger
Keyword(s):  
Genetic Diversity ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Phenotypic Variability ◽  
Genome Wide Association ◽  
Septoria Tritici Blotch ◽  
Septoria Tritici ◽  
Genome Wide ◽  
A Genome ◽  
Wheat Landraces

Abstract Septoria tritici blotch (STB), caused by the fungus Zymoseptoria tritici, is a major constraint in global wheat production. The lack of genetic diversity in modern elite wheat cultivars largely hinders the improvement of STB resistance. Wheat landraces are reservoirs of untapped genetic diversity, which can be exploited to find novel STB resistance genes or alleles. Here, we characterized 188 Swiss wheat landraces for resistance to STB using four Swiss Z. tritici isolates. We used a genome-wide association study (GWAS) to identify genetic variants associated with the amount of lesion and pycnidia production by the fungus. The majority of the landraces were highly resistant for both traits to the isolate 1E4, indicating a gene-for-gene relationship, while higher phenotypic variability was observed against other isolates. GWAS detected a significant SNP on chromosome 3A that was associated with both traits in the isolate 1E4. The resistance response against 1E4 was likely controlled by the Stb6 gene. Sanger sequencing revealed that the majority of these ~100-year-old landraces carry the Stb6 resistance allele. This indicates the importance of this gene in Switzerland during the early 1900s for disease control in the field. Our study demonstrates the importance of characterizing historic landrace collections for STB resistance to provide valuable information on resistance variability and contributing alleles. This will help breeders in the future to make decisions on integrating such germplasms in STB resistance breeding.

scholarly journals Allelotyping of Follicular Thyroid Carcinoma: Frequent Allelic Losses in Chromosome Arms 7q, 11p, and 22q

2001 ◽  
Vol 86 (9) ◽  
pp. 4268-4272 ◽  
Author(s):  
Yutaka Kitamura ◽  
Kazuo Shimizu ◽  
Koichi Ito ◽  
Shigeo Tanaka ◽  
Mitsuru Emi
Keyword(s):  
Thyroid Carcinoma ◽  
Follicular Thyroid Carcinoma ◽  
Allelic Loss ◽  
Mean Frequency ◽  
Thyroid Carcinomas ◽  
Real Frequency ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Mechanisms ◽  
The Mean

The genetic mechanisms involved in development of follicular thyroid carcinoma are poorly understood, although allelic losses (LOH) in this type of tumor have been reported in small panels of follicular thyroid carcinomas examined in earlier studies. To clarify the real frequency of allelic loss we carried out a genome-wide allelotyping study of 66 follicular thyroid carcinomas using 39 microsatellite markers representing all nonacrocentric autosomal arms. The mean frequency of LOH was 9.2%, and the mean fractional allelic loss was 0.09. The most frequent allelic losses were detected in 7q (28%), 11p (28%), and 22q (41%). When we compared these results with our previous allelotyping studies using identical markers in other types of thyroid cancers, the 9.2% mean frequency of allelic loss detected in follicular thyroid carcinomas was higher than that in papillary thyroid carcinomas (3%), but not as high as that detected in anaplastic thyroid carcinomas (20%). Frequent allelic losses of markers on chromosomes 7q, 11p, and 22q suggest locations to examine for the presence of suppressor genes associated with the development of follicular thyroid carcinoma.

scholarly journals A Genome-Wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans

PLoS Genetics ◽  
2012 ◽  
Vol 8 (9) ◽  
pp. e1002932 ◽  
Author(s):  
Fan Liu ◽  
Fedde van der Lijn ◽  
Claudia Schurmann ◽  
Gu Zhu ◽  
M. Mallar Chakravarty ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Facial Morphology ◽  
Genome Wide ◽  
A Genome

Serial genome-wide sequencing of cell-free DNA (cfDNA) by assays used in non-invasive prenatal testing (NIPT) to identify copy number alterations (CNAs) associated with immunotherapy response.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14533-e14533
Author(s):  
Aaron Goodman ◽  
Taylor Jensen ◽  
Shumei Kato ◽  
Christopher Ellison ◽  
Lisa Tran ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Peripheral Blood ◽  
Prenatal Testing ◽  
Quantitative Detection ◽  
Initial Increase ◽  
Continuous Increase ◽  
Genome Wide ◽  
A Genome ◽  
The Mean ◽  
Sustained Increase

e14533 Background: cfDNA derived from tumor cells can be detected in the plasma of many cancer patients. Noninvasive methods to detect CNAs have been developed to detect chromosomal abnormalities in the setting of prenatal screening. We hypothesized that similar methods can be used to enable quantitative detection of CNAs in cfDNA, as represented by a genome instability number (GIN), in patients with cancer and used to monitor response to immunotherapy. Methods: Peripheral blood for CNA analysis was collected from patients with diverse cancers for whom immunotherapy was planned. Plasma was separated from peripheral blood using centrifugation. cfDNA was collected and subjected to low-coverage, genome-wide sequencing. CNAs were detected using methods developed for noninvasive prenatal testing. GIN was calculated as the cumulative sum of the deviation from baseline for all detected autosomal CNAs. The current analysis focused on patients with a complete or partial response (CR/PR) or progressive disease (PD). Results: Of 48 patients, 11 (23%) attained CR/PR; 17 (35%), PD; 20, stable disease. Twelve of the 28 patients (43%) with CR/PR (5 (42%)) or PD (7 (58%)) had a GIN value consistent with the presence of CNAs at treatment initiation and ≥ 1 additional sample for comparison. Four of the 5 patients with CR/PR had a decrease in their GIN from their baseline while all 7 patients with PD had a sustained increase in their GIN. The mean (standard error of the mean (SEM)) change in GIN from maximum to minimum for responders was –2753.8 (+/-1643); mean (SEM) change in GIN from minimum to maximum for progressors was 1373.76 (+/-576) (p = 0.0221). Interestingly, 3 of the 5 responders had an initial increase in their GIN after 2-3 weeks of treatment followed by a decline, while all 7 progressors had a continuous increase in their GIN. Conclusions: GIN can be used to monitor response to immune checkpoint inhibitors in cancer patients. Serial evaluation shows an initial GIN increase followed by decline in patients who eventually attain CR/PR, but a sustained increase in patients with progression.

scholarly journals Behavioral individuality reveals genetic control of phenotypic variability

2014 ◽  
Author(s):  
Julien F Ayroles ◽  
Sean M Buchanan ◽  
Chelsea Jenney ◽  
Kyobi Skutt-Kakaria ◽  
Jennifer Grenier ◽  
...  
Keyword(s):  
Genetic Control ◽  
Genome Wide Association Study ◽  
Phenotypic Variability ◽  
Central Complex ◽  
Null Alleles ◽  
Behavioral Variability ◽  
Phenotypic Differences ◽  
Genome Wide ◽  
A Genome ◽  
Inducible Rnai

Variability is ubiquitous in nature and a fundamental feature of complex systems. Few studies, however, have investigated variance itself as a trait under genetic control. By focusing primarily on trait means and ignoring the effect of alternative alleles on trait variability, we may be missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used a panel of Drosophila inbred lines and focused on locomotor handedness, in an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals while others had low levels. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicated a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We have validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. This study reveals the constellation of phenotypes that can arise from a single genotype and it shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variability. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype.

scholarly journals Behavioral idiosyncrasy reveals genetic control of phenotypic variability

2015 ◽  
Vol 112 (21) ◽  
pp. 6706-6711 ◽  
Author(s):  
Julien F. Ayroles ◽  
Sean M. Buchanan ◽  
Chelsea O’Leary ◽  
Kyobi Skutt-Kakaria ◽  
Jennifer K. Grenier ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Phenotypic Variability ◽  
Genetic Effects ◽  
Central Complex ◽  
Null Alleles ◽  
Behavioral Variability ◽  
Phenotypic Differences ◽  
Genome Wide ◽  
A Genome ◽  
Inducible Rnai

Quantitative genetics has primarily focused on describing genetic effects on trait means and largely ignored the effect of alternative alleles on trait variability, potentially missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study the genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used Drosophila inbred lines and measured the spontaneous locomotor behavior of flies walking individually in Y-shaped mazes, focusing on variability in locomotor handedness, an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals, whereas lines with low variability behaved as although they tossed a coin at each left/right turn decision. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicates a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. Our study reveals the constellation of phenotypes that can arise from a single genotype and shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variabililty. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype.

Sign in / Sign up

Export Citation Format

Share Document