Identification of rare variants of allergic rhinitis based on whole genome sequencing and gene expression profiling: A preliminary investigation in four families

AbstractHuman population isolates provide a snapshot of the impact of historical demographic processes on population genetics. Such data facilitate studies of the functional impact of rare sequence variants on biomedical phenotypes, as strong genetic drift can result in higher frequencies of variants that are otherwise rare. We present the first whole genome sequencing (WGS) study of the VIKING cohort, a representative collection of samples from the isolated Shetland population in northern Scotland, and explore how its genetic characteristics compare to a mainland Scottish population. Our analyses reveal the strong contributions played by the founder effect and genetic drift in shaping genomic variation in the VIKING cohort. About one tenth of all high-quality variants discovered are unique to the VIKING cohort or are seen at frequencies at least ten fold higher than in more cosmopolitan control populations. Multiple lines of evidence also suggest relaxation of purifying selection during the evolutionary history of the Shetland isolate. We demonstrate enrichment of ultra-rare VIKING variants in exonic regions and for the first time we also show that ultra-rare variants are enriched within regulatory regions, particularly promoters, suggesting that gene expression patterns may diverge relatively rapidly in human isolates.Author SummaryPopulation isolates provide a valuable window on the roles of rare genetic variation in human phenotypes, as a result of their unusual evolutionary histories, that often lead to relatively high frequencies of variants that are exceptionally rare elsewhere. Such populations show increased levels of background relatedness among individuals and are often subject to stronger genetic drift, leading to a higher frequency of deleterious variants. Here, for the first time, we present whole genome sequencing data from the Shetland population in Northern Scotland, encompassing 500 individuals, and compare these genomes to the mainland Scottish population. As expected we find the imprint of Shetland population history in the Shetland genome, with strong evidence for founder effects and genetic drift, but we also discover a relaxation of selective constraint across the genome. These influences have combined to endow the Shetland genome with thousands of ultra-rare genetic variants, not observed previously in other populations. Surprisingly these variants are significantly enriched in functional regions including protein coding regions of genes and regulatory elements. Among regulatory regions, promoters are particularly enriched for ultra-rare variants, suggesting the potential for rapid divergence of gene expression in isolates.

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Multi-OMICS and Molecular Biology Perspective in Buffalo Genome

Journal of Buffalo Science ◽

10.6000/1927-520x.2021.10.04 ◽

2021 ◽

pp. 21-31

Author(s):

Suranjana Sikdar ◽

◽

Tuhin Das ◽

Emran Hossain Sajib ◽

Kazi Mahbub Ur Rahman Rahman ◽

...

Keyword(s):

Gene Expression ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Expression Profiling ◽

Phenotypic Diversity ◽

Genomic Research ◽

Phenotypic Traits ◽

Whole Genome ◽

Single Nucleotide ◽

Geographical Regions

The bovine species buffalo was domesticated from its wild strain Bubalus arnee and is widely used livestock in southern Asia. There are two distinct types of Buffalo- the swamp buffalo (B. bubalis kerebau) and the river buffalo (B. bubalis bubalis), which diverged from the wild Asian water buffalo and then evolved in separate geographical regions. Several research studies performed on buffalo, like- characterization of trait-specific Single Nucleotide Polymorphism (SNP), genetic and phenotypic diversity, gene prediction and function annotation, mapping of the draft genome, have helped our understanding of the buffalo genome. Some advanced discovery as identification of Single Nucleotide Variant (SNVs), Simple Sequence Repeats (SSR) marker and their association with various phenotypic traits, MicroRNA's expression profiling, whole-genome sequencing, etc. have also enabled us to track the chromosomal evolution, physiological processes, and gene expression of buffalo. Proper enhancement of these traits can lead us to apply multi-omics-based tools for better animal health and production. Recent advancement in genomic research on buffalo is being accelerated with the association of modern tools like- Genome-Wide Association Study (GWAS), genotyping by sequencing, epigenomic screening, microRNA's expression profiling, microarray technology, and whole-genome sequencing. All these tools bear great significance in breed up-gradation, identification of the phylogenetic relationship between species in proteome and genomic level, study gene expression level, diagnose diseases or developmental stages, phenotypic diversity, etc. All this knowledge paved the way for better optimization of production efficiency, product quality, and resistance to certain health hazards.

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The crest phenotype in domestic chicken is caused by a 197 bp duplication in the intron of HOXC10

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkaa048 ◽

2021 ◽

Author(s):

Jingyi Li ◽

Mi-Ok Lee ◽

Brian W Davis ◽

Ping Wu ◽

Shu-Man Hsieh-Li ◽

...

Keyword(s):

Gene Expression ◽

Whole Genome Sequencing ◽

Diagnostic Test ◽

Genome Sequencing ◽

Ectopic Expression ◽

Body Region ◽

Whole Genome ◽

Dorsal Skin ◽

Conserved Sequence ◽

Evolutionarily Conserved

Abstract The Crest mutation in chicken shows incomplete dominance and causes a spectacular phenotype in which the small feathers normally present on the head are replaced by much larger feathers normally present only in dorsal skin. Using whole genome sequencing, we show that the crest phenotype is caused by a 197 bp duplication of an evolutionarily conserved sequence located in the intron of HOXC10 on chromosome 33. A diagnostic test showed that the duplication was present in all 54 crested chickens representing eight breeds and absent from all 433 non-crested chickens representing 214 populations. The mutation causes ectopic expression of at least five closely linked HOXC genes, including HOXC10, in cranial skin of crested chickens. The result is consistent with the interpretation that the crest feathers are caused by an altered body region identity. The upregulated HOXC gene expression is expanded to skull tissue of Polish chickens showing a large crest often associated with cerebral hernia, but not in Silkie chickens characterized by a small crest, both homozygous for the duplication. Thus, the 197 bp duplication is required for the development of a large crest and susceptibility to cerebral hernia because only crested chicken show this malformation. However, this mutation is not sufficient to cause herniation because this malformation is not present in breeds with a small crest, like Silkie chickens.

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E. coli NF73-1 Isolated From NASH Patients Aggravates NAFLD in Mice by Translocating Into the Liver and Stimulating M1 Polarization

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.535940 ◽

2020 ◽

Vol 10 ◽

Author(s):

Yifan Zhang ◽

Weiwei Jiang ◽

Jun Xu ◽

Na Wu ◽

Yang Wang ◽

...

Keyword(s):

Gene Expression ◽

Comparative Genomics ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Normal Diet ◽

Specific Gene ◽

Whole Genome ◽

Metabolic Switch ◽

M1 Macrophages ◽

E Coli

ObjectiveThe gut microbiota is associated with nonalcoholic fatty liver disease (NAFLD). We isolated the Escherichia coli strain NF73-1 from the intestines of a NASH patient and then investigated its effect and underlying mechanism.Methods16S ribosomal RNA (16S rRNA) amplicon sequencing was used to detect bacterial profiles in healthy controls, NAFLD patients and NASH patients. Highly enriched E. coli strains were cultured and isolated from NASH patients. Whole-genome sequencing and comparative genomics were performed to investigate gene expression. Depending on the diet, male C57BL/6J mice were further grouped in normal diet (ND) and high-fat diet (HFD) groups. To avoid disturbing the bacterial microbiota, some of the ND and HFD mice were grouped as “bacteria-depleted” mice and treated with a cocktail of broad-spectrum antibiotic complex (ABX) from the 8th to 10th week. Then, E. coli NF73-1, the bacterial strain isolated from NASH patients, was administered transgastrically for 6 weeks to investigate its effect and mechanism in the pathogenic progression of NAFLD.ResultsThe relative abundance of Escherichia increased significantly in the mucosa of NAFLD patients, especially NASH patients. The results from whole-genome sequencing and comparative genomics showed a specific gene expression profile in E. coli strain NF73-1, which was isolated from the intestinal mucosa of NASH patients. E. coli NF73-1 accelerates NAFLD independently. Only in the HFD-NF73-1 and HFD-ABX-NF73-1 groups were EGFP-labeled E. coli NF73-1 detected in the liver and intestine. Subsequently, translocation of E. coli NF73-1 into the liver led to an increase in hepatic M1 macrophages via the TLR2/NLRP3 pathway. Hepatic M1 macrophages induced by E. coli NF73-1 activated mTOR-S6K1-SREBP-1/PPAR-α signaling, causing a metabolic switch from triglyceride oxidation toward triglyceride synthesis in NAFLD mice.ConclusionsE. coli NF73-1 is a critical trigger in the progression of NAFLD. E. coli NF73-1 might be a specific strain for NAFLD patients.

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