Introduction to Functional Variants

Functional variants contributing to EOCAD risk are identified by high-depth whole-exome sequencing.

In summary, whole exome sequencing in Pima Indians has identified potentially functional variants in BBS9 that may increase risk for obesity through leptin signaling.

Finally, we identified a group of two SNPs with increased minor allele frequencies as potential functional variants.

Here, we sequenced 547 genes from 1,102 patients with NDDs and validated 1,271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes.

Although laborious, this multistep procedure for classifying variants allowed the identification of potentially functional variants for milk protein genes.

OBJECTIVE This study, in a Southern Chinese population, was aimed to clarify the roles in HCC incidence of the rs7574865 and other two potentially functional variants, rs897200 and rs1031507 in STAT4.

Fine-mapping of these enhancers nominates candidate functional variants that likely modify AD risk by regulating gene expression in myeloid cells.

Candidate functional variants were tested for association with gout by multivariable-adjusted regression analysis in 2,528 individuals of Polynesian ancestry.

We identified 654 candidate genes including 481 shared candidate genes carrying putative functional variants in at least two disorders.

7% of 270) had evidence of cis-regulation by putative functional variants via proximal promoter or distal enhancer-promoter interactions.

We validate CRAIDE by evolving novel functional variants of an auxotrophic marker gene, and by conferring resistance to a toxic amino acid analogue in baker's yeast Saccharomyces cerevisiae with a mutation rate >3,000-fold higher compared to spontaneous native rate, thus enabling the first demonstrations of in vivo delivery and information transfer from long evolving RNA donor templates into genomic context without the use of in vitro supplied and pre-programmed repair donors.

The introduction of these novel functional variants into marker-assisted breeding programs is expected to have a relevant effect on PTB control.

Thus, here we sought to determine the occurrence of rare functional variants in a large Italian MS multiplex family with five affected members.

Our study revealed several rare functional variants, which form eight novel and rare haplotypes of CYP2C9 (CYP2C9*63–*70).

This study aimed to analyze the association between two functional variants of the miR-146a gene and primary knee OA in Mexican mestizo population.

3 region contains at least two functional variants that map to distinct enhancers and impact CRC risk through modulation of GREM1 expression.

To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing ‘depression-like’ shifts in cortical gene expression.

Certain common functional variants including NUDT15 13:48611934 G/A (rs186364861), UGT1A1 2:234676872 C/T (rs34946978), and ALDH2 12:112241766 G/A (rs671) were population-specific for CMDB Chinese because they were absent (with a zero of variant allele frequency) or very rare in other gnomAD populations.

The analysis of whole-genome sequence (WGS) data from 21 bulls revealed functional variants that are associated with DHC, including a structural rearrangement involving ASIP ( ASIP -SV1).

Patient’s genotyping revealed functional variants associated with severe infections.

Using experimentally determined regulatory variants from iPS cell-derived neurons, we show that MetaChrom predicts functional variants more accurately than existing non-coding variant scoring tools.

Here we present a computational model, Score of Unified Regulatory Features (SURF), that predicts functional variants in enhancer and promoter elements.

The non-coding genome is substantially larger than the protein-coding genome, but the lack of appropriate methodologies for identifying functional variants limits genetic association studies.

Identifying functional variants underlying disease risk and adoption of personalized medicine are currently limited by the challenge of interpreting the functional consequences of genetic variants.

These functional variants provide a new understanding of the genetic basis for HT tolerance in male reproductive organs.

These functional variants are biomarkers of infection or aGVHD death and could facilitate donor selection, prophylaxis, and a conditioning regimen to reduce post-HCT mortality.

Our findings suggest moderately altered MRP4 activity in six out of nine predicted functional variants with likely different mechanisms and substrate-specific effects.

Lastly, the authors focus in on AT-II and identify additional predicted functional variants within several known loci, including 22q12.

Results Analysis of all the targeted DNA sequences for the whole patient group indicated 121 different functional variants.

ATP1A3, a mutated gene for AHC, RDP, and CAPOS, is also associated with polymicrogyria by different functional variants.

Meanwhile, benefitting from extensive annotations generated, CARMEN provides mechanism hints on predicted expression-modulating variants, enabling effectively characterizing functional variants involved in gene expression and disease-related phenotypes.

3D modeling highlighted several non-conservative SNP variants compared to the bovine, as well as putative functional variants involved in the stability of the myostatin dimer.

Functional variants may influence SARS-CoV-2 infection risk and severity of Coronavirus disease 2019 (COVID-19) as well.

Additionally genetic mapping of TRCP6 functional variants may provide a new screening tool to determine increased risk of developing heart failure.

A key to understanding MDD pathophysiology will be elucidation of which SNPs are functional and how such functional variants biologically converge to elicit the disease.

A key to understanding MDD pathophysiology will be elucidation of which SNPs are functional and how such functional variants biologically converge to elicit the disease.

Interactive visualization of tissue-specific eQTLs can facilitate our understanding of functional variants relevant to disease-related traits.

Interactive visualization of tissue-specific eQTLs or splice QTLs (sQTLs) can facilitate our understanding of functional variants relevant to disease-related traits.

The successes of GWAS have triggered thoughts about how to move beyond identification of loci (which contain a very large number of variants), to identification of the functional variants within them that actually contribute to the risk for the traits, and from there to identifying the genes, pathways, and mechanisms involved.

Lastly, the authors focus in on AT-II and identify additional predicted functional variants within several known loci, including 22q12.

Here, we combine genetic data, epigenomic data, and CRISPR activation (CRISPRa) assays to screen for functional variants regulating IRF8 expression.

Another issue was that we currently do not know the full repertoire of functional variants regulating human gene expression and, therefore, candidate studies were unlikely to have selected the correct regulatory variants to test for association in the first place.

In the first two categories, the authors find several potential functional variants affecting genes with functions in extracellular matrix organisation and muscle contraction, but further interpretation is hampered because many of these genes remain poorly characterised.

This study recognized chr4:73206169-73208244 as a key region harboring functional variants affecting the growth of chickens.