scholarly journals A Novel Genetic Marker for the C9orf72 Repeat Expansion in the Finnish Population

2021 ◽  
pp. 1-8
Author(s):  
Hannah Rostalski ◽  
Ville Korhonen ◽  
Teemu Kuulasmaa ◽  
Eino Solje ◽  
Johanna Krüger ◽  
...  
Keyword(s):  
Strong Association ◽  
Normal Pressure ◽  
Repeat Expansion ◽  
Risk Haplotype ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
C9orf72 Repeat Expansion ◽  
Inph Patient ◽  
The Uk ◽  
All Diseases

Background: C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods. Objective: Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp. Methods: We elucidated the potential of the previously described Finnish risk haplotype, defined by the SNP rs3849942, to identify potential C9exp carriers among 218,792 Finns using the FinnGen database. The haplotype approach was first tested in an idiopathic normal pressure hydrocephalus (iNPH) patient cohort (European Alzheimer’s Disease DNA BioBank) containing C9exp carriers by comparing intermediate (15–30) and full-length (>  60 repeats) C9exp carriers (n = 41) to C9exp negative patients (<  15 repeats, n = 801). Results: In this analysis, rs3849942 was associated with carriership of C9exp (OR 8.44, p <  2×10–15), while the strongest association was found with rs139185008 (OR 39.4, p <  5×10–18). Unbiased analysis of rs139185008 in FinnGen showed the strongest association with FTLD (OR 4.38, 3×10–15) and motor neuron disease ALS (OR 5.19, 3×10–21). rs139185008 was the top SNP in all diseases (iNPH, FTLD, ALS), and further showed a strong association with ALS in the UK Biobank (p = 9.0×10–8). Conclusion: Our findings suggest that rs139185008 is a useful marker to identify potential C9exp carriers in the genotyped cohorts and biobanks originating from Finland.

scholarly journals Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 808
Author(s):  
Laura Pérez-Lago ◽  
Teresa Aldámiz-Echevarría ◽  
Rita García-Martínez ◽  
Leire Pérez-Latorre ◽  
Marta Herranz ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Evolutionary Dynamics ◽  
Viral Evolution ◽  
Special Focus ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
New Variant ◽  
History Of ◽  
Evolution Dynamics ◽  
The Uk

A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases.

Lifestyle factors and genetic variants on two biological age measures: evidence from 94,443 Taiwan Biobank participants

2021 ◽  
Author(s):  
Wan-Yu Lin
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Lifestyle Factors ◽  
Biological Age ◽  
Biological Aging ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
The Uk

Abstract Background Biological age (BA) can be estimated by phenotypes and is useful for predicting lifespan and healthspan. Levine et al. proposed a PhenoAge and a BioAge to measure BA. Although there have been studies investigating the genetic predisposition to BA acceleration in Europeans, little has been known regarding this topic in Asians. Methods I here estimated PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 94,443 Taiwan Biobank (TWB) participants, wherein 25,460 TWB1 subjects formed a discovery cohort and 68,983 TWB2 individuals constructed a replication cohort. Lifestyle factors and genetic variants associated with PhenoAgeAccel and BioAgeAccel were investigated through regression analysis and a genome-wide association study (GWAS). Results A unit (kg/m 2) increase of BMI was associated with a 0.177-year PhenoAgeAccel (95% C.I. = 0.163~0.191, p = 6.0×) and 0.171-year BioAgeAccel (95% C.I. = 0.165~0.177, p = 0). Smokers on average had a 1.134-year PhenoAgeAccel (95% C.I. = 0.966~1.303, p = 1.3×) compared with non-smokers. Drinkers on average had a 0.640-year PhenoAgeAccel (95% C.I. = 0.433~0.847, p = 1.3×) and 0.193-year BioAgeAccel (95% C.I. = 0.107~0.279, p = 1.1×) relative to non-drinkers. A total of 11 and 4 single-nucleotide polymorphisms (SNPs) were associated with PhenoAgeAccel and BioAgeAccel (p&lt;5× in both TWB1 and TWB2), respectively. Conclusions A PhenoAgeAccel-associated SNP (rs1260326 in GCKR) and two BioAgeAccel-associated SNPs (rs7412 in APOE; rs16998073 near FGF5) were consistent with the finding from the UK Biobank. The lifestyle analysis shows that prevention from obesity, cigarette smoking, and alcohol consumption is associated with a slower rate of biological aging.

scholarly journals Evidence for a genetic sex determination in Cnidaria, the Mediterranean red coral ( Corallium rubrum )

2017 ◽  
Vol 4 (3) ◽  
pp. 160880 ◽  
Author(s):  
M. Pratlong ◽  
A. Haguenauer ◽  
S. Chenesseau ◽  
K.  Brener ◽  
G. Mitta ◽  
...  
Keyword(s):  
Sex Determination ◽  
Strong Association ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Evolutionary Forces ◽  
Corallium Rubrum ◽  
Red Coral ◽  
Determination System ◽  
Sex Determination System ◽  
Male Specific

Sexual reproduction is widespread among eukaryotes, and the sex-determining processes vary greatly among species. While genetic sex determination (GSD) has been intensively described in bilaterian species, no example has yet been recorded among non-bilaterians. However, the quasi-ubiquitous repartition of GSD among multicellular species suggests that similar evolutionary forces can promote this system, and that these forces could occur also in non-bilaterians. Studying sex determination across the range of Metazoan diversity is indeed important to understand better the evolution of this mechanism and its lability. We tested the existence of sex-linked genes in the gonochoric red coral ( Corallium rubrum , Cnidaria) using restriction site-associated DNA sequencing. We analysed 27 461 single nucleotide polymorphisms (SNPs) in 354 individuals from 12 populations including 53 that were morphologically sexed. We found a strong association between the allele frequencies of 472 SNPs and the sex of individuals, suggesting an XX/XY sex-determination system. This result was confirmed by the identification of 435 male-specific loci. An independent test confirmed that the amplification of these loci enabled us to identify males with absolute certainty. This is the first demonstration of a GSD system among non-bilaterian species and a new example of its convergence in multicellular eukaryotes.

Differentiation between wild-type and vaccines strains of varicella zoster virus (VZV) based on four single nucleotide polymorphisms

2017 ◽  
Vol 145 (12) ◽  
pp. 2618-2625
Author(s):  
L. JIN ◽  
S. XU ◽  
P. A. C. MAPLE ◽  
W. XU ◽  
K. E. BROWN
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Varicella Zoster Virus ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Chain Reactions ◽  
Varicella Zoster ◽  
Polymerase Chain Reactions ◽  
Set Up ◽  
The Uk

SummaryVaricella–zoster virus (VZV) infection (chickenpox) results in latency and subsequent reactivation manifests as shingles. Effective attenuated vaccines (vOka) are available for prevention of both illnesses. In this study, an amplicon-based sequencing method capable of differentiating between VZV wild-type (wt) strains and vOka vaccine is described. A total of 44 vesicular fluid specimens collected from 43 patients (16 from China and 27 from the UK) with either chickenpox or shingles were investigated, of which 10 had received previous vaccination. Four sets of polymerase chain reactions were set up simultaneously with primers amplifying regions encompassing four single nucleotide polymorphisms (SNPs), ‘69349-106262-107252-108111’. Nucleotide sequences were generated by Sanger sequencing. All samples except one had a wt SNP profile of ‘A-T-T-T’. The sample collected from a patient who received vaccine 7–10 days ago, along with VZV vaccine preparations, Zostavax and Baike-varicella gave a SNP profile ‘G-C-C-C’. The results show that this method can distinguish vaccine-derived virus from wt viruses from main four clades, (clades 1–4) and should be of utility worldwide.

scholarly journals SNP rs2073618 of the Osteoprotegerin Gene Is Associated with Diabetic Retinopathy in Slovenian Patients with Type 2 Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Sara Mankoč Ramuš ◽  
Tina Kumše ◽  
Mojca Globočnik Petrovič ◽  
Daniel Petrovič ◽  
Ines Cilenšek
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Strong Association ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Regulatory Molecule ◽  
Codominant Model ◽  
Osteoprotegerin Gene

Recent studies indicate that osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. Also, a strong association was observed between circulation OPG and microvascular complication. By considering the possible role of OPG in diabetic retinopathy (DR) we examined two of the most studied polymorphisms of the OPG genes rs2073618 (located in exon I) and rs3134069 (located in the promoter region) and their relation to DR in Slovenian patients with type 2 diabetes. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype (codominant model for rs2073618). Furthermore, the combined effect of single nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 on the DR was stronger than that of each SNP alone. The odds ratio (OR) for individuals with CC genotype (rs2073618) and AA genotype (rs3134069) compared with carriers of CG/GG (rs2073618) + AA (rs3134069) was 2.54 (95% CI = 1.26–5.13, ). To conclude, these results indicate that SNPs in the OPG gene may be implicated in the pathogenesis of DR.

scholarly journals Comparison between the HLA-B∗58 : 01 Allele and Single-Nucleotide Polymorphisms in Chromosome 6 for Prediction of Allopurinol-Induced Severe Cutaneous Adverse Reactions

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Niwat Saksit ◽  
Nontaya Nakkam ◽  
Parinya Konyoung ◽  
Usanee Khunarkornsiri ◽  
Wongwiwat Tassaneeyakul ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Strong Association ◽  
Chromosome 6 ◽  
Surrogate Markers ◽  
Nucleotide Polymorphisms ◽  
Thai Population ◽  
Single Nucleotide ◽  
Life Threatening ◽  
Sensitivity Specificity ◽  
Degree Of Association

Severe cutaneous adverse drug reactions (SCARs) are life-threatening reactions. The strong association between the HLA-B∗58 : 01 allele and allopurinol-induced SCARs is well recognized. Screening for HLA-B∗58 : 01 allele before prescribing allopurinol in some populations has been recommended. Several single-nucleotide polymorphisms (SNPs) in chromosome 6 have been found to be tightly linked with the HLA allele, and these SNPs have been proposed as surrogate markers of the HLA-B∗58 : 01 allele. This study aimed to evaluate the association between three SNPs in chromosome 6 and allopurinol-induced SCARs in a Thai population. The linkage disequilibrium between the HLA-B∗58 : 01 allele and these SNPs was also evaluated. Results showed that three SNPs including rs9263726, rs2734583, and rs3099844 were significantly associated with allopurinol-induced SCARs but with a lower degree of association when compared with the HLA-B∗58 : 01 allele. The sensitivity, specificity, PPV, and NPV of these SNPs were comparable to those of the HLA-B∗58 : 01 allele. Although detection of the SNP is simpler and less expensive compared with that of the HLA-B∗58 : 01 allele, these SNPs were not perfectly linked with the HLA-B∗58 : 01 allele. Screening using these SNPs as surrogate markers of the HLA-B∗58 : 01 allele to avoid SCARs prior to allopurinol administration needs caution because of their imperfect linkage with the HLA-B∗58 : 01 allele.

MicroRNA 146a Polymorphisms and Expression in Indian Children with Acute Lymphoblastic Leukemia

2018 ◽  
Vol 50 (3) ◽  
pp. 249-253 ◽  
Author(s):  
Helen Jemimah Devanandan ◽  
Vettriselvi Venkatesan ◽  
Julius Xavier Scott ◽  
Latha Sneha Magatha ◽  
Solomon Franklin Durairaj Paul ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Childhood Leukemia ◽  
Lymphoblastic Leukemia ◽  
Malignant Neoplasms ◽  
Risk Haplotype ◽  
Nucleotide Polymorphisms ◽  
Indian Children ◽  
Single Nucleotide ◽  
Protective Haplotype ◽  
Asian Children

Abstract Background MicroRNAs (miR) have been reported to be involved in hematopoiesis and in the pathogenesis of several hematological malignant neoplasms. Single-nucleotide polymorphisms (SNPs) in human miR genes may alter the expression of those genes and influence the predisposition to childhood leukemia. Objective To evaluate the association of rs2910164 G>C, rs57095329 A>G and the expression of miRNA-146a in ethnic South Asian children with acute lymphoblastic leukemia (ALL). Method Genotyping and expression analysis using TaqMan Small RNA Assay was performed on 71 patients with pathologically confirmed ALL and 74 control individuals. Results No statistically significant association was found between the 2 SNPs, its expression levels, and ALL risk. Conclusion Haplotype analysis indicated a combination of allele A of rs57095329 and allele G of rs2910164 could represent a risk haplotype and an allele combination of G of rs57095329 and G of rs2910164 could represent a protective haplotype for ALL.

Do Serum Urate–associated Genetic Variants Influence Gout Risk in People Taking Diuretics? Analysis of the UK Biobank

2020 ◽  
Vol 47 (11) ◽  
pp. 1704-1711
Author(s):  
Ravi K. Narang ◽  
Greg Gamble ◽  
Amanda J. Phipps-Green ◽  
Ruth Topless ◽  
Murray Cadzow ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Loop Diuretic ◽  
Genetic Risk Score ◽  
Serum Urate ◽  
Nucleotide Polymorphisms ◽  
Thiazide Diuretics ◽  
Uk Biobank ◽  
Single Nucleotide ◽  
Primary Gout ◽  
The Uk

ObjectiveThe aim of this study was to determine whether serum urate (SU)–associated genetic variants differ in their influence on gout risk in people taking a diuretic compared to those not taking a diuretic.MethodsThis research was conducted using the UK Biobank Resource (n = 359,876). Ten SU-associated single-nucleotide polymorphisms (SNP) were tested for their association with gout according to diuretic use. Gene-diuretic interactions for gout association were tested using a genetic risk score (GRS) and individual SNP by logistic regression adjusting for relevant confounders.ResultsAfter adjustment, use of a loop diuretic was positively associated with prevalent gout (OR 2.34, 95% CI 2.08–2.63), but thiazide diuretics were inversely associated with prevalent gout (OR 0.60, 95% CI 0.55–0.66). Compared with a lower GRS (< mean), a higher GRS (≥ mean) was positively associated with gout in those not taking diuretics (OR 2.63, 2.49–2.79), in those taking loop diuretics (OR 2.04, 95% CI 1.65–2.53), in those taking thiazide diuretics (OR 2.70, 2.26–3.23), and in those taking thiazide-like diuretics (OR 2.11, 95% CI 1.37–3.25). No nonadditive gene-diuretic interactions were observed.ConclusionIn people taking diuretics, SU-associated genetic variants contribute strongly to gout risk, with a similar effect to that observed in those not taking a diuretic. These findings suggest that the contribution of genetic variants is not restricted to people with “primary” gout, and that genetic variants can play an important role in gout susceptibility in the presence of other risk factors.

scholarly journals Investigating neurotrophin genetics and hippocampal volume

2022 ◽  
Author(s):  
Jaisalmer de Frutos ◽  
Michael Vacher ◽  
Tenielle Porter ◽  
Simon Laws ◽  
Belinda Brown
Keyword(s):  
Structural Integrity ◽  
Hippocampal Volume ◽  
Brain Regions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cognitively Normal ◽  
Factor Gene ◽  
Tyrosine Kinase 2 ◽  
Growth Factor Gene ◽  
The Uk

As individuals get older, the structural integrity of brain regions becomes progressively diminished. Neurotrophic function might aid in preventing such losses through increased synaptogenesis and neurogenesis, particularly in the hippocampus, a brain structure relevant for cognitive function. However, the carriage of certain genetic alleles for genes involved in neurotrophic function might restrain the effectiveness of neurotrophin signalling, hindering neuroprotection. Yet, research on the contribution of single nucleotide polymorphisms (SNPs) within genes coding for neurotrophins and their receptors to hippocampal volumes is scarce, with the exception of rs6265 within the brain-derived neurotrophic factor gene. Therefore, the aim of this study was to identify SNPs within genes involved neurotrophic function that are associated with hippocampal volume in a sample of 23,776 cognitively normal older adults from the UK Biobank. We found that, in individuals older than 50, homozygote carriage of the major alleles rs4839435-A within nerve growth factor gene and rs56405676-T within the neurotrophic receptor tyrosine kinase 2 gene, were associated with increase hippocampal volumes, compared to carriage of 1 or 2 copies of the minor alleles. However, only rs56405676-T was significantly associated with greater hippocampal volumes in individuals older than 60. Hence this study might serve to identify populations at higher risk of hippocampal attrition and cognitive decline.

scholarly journals Using deep learning to analyze the compositeness of musculoskeletal aging reveals that spine, hip and knee age at different rates, and are associated with different genetic and non-genetic factors

2021 ◽  
Author(s):  
Alan Le Goallec ◽  
Samuel Diai ◽  
Sasha Collin ◽  
Theo Vincent ◽  
Chirag J Patel
Keyword(s):  
Musculoskeletal System ◽  
Genetic Factors ◽  
Pearson Correlation ◽  
The Body ◽  
World Population ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
X Ray ◽  
The Uk ◽  
Full Body

With age, the musculoskeletal system undergoes significant changes, leading to diseases such as arthritis and osteoporosis. Due to the aging of the world population, the prevalence of such diseases is therefore expected to starkly increase in the coming decades. While numerous biological age predictors have been developed to assess musculoskeletal aging, it remains unclear whether these different approaches and data capture a single aging process, or if the diverse joints and bones in the body age at different rates. In the following, we leverage 42,000 full body, spine, hip and knee X-ray images and musculoskeletal biomarkers from the UK Biobank and use artificial intelligence to build the most accurate musculoskeletal aging predictor to date (RMSE=2.65+/-0.01 years; R-Squared=87.6+/-0.1%). Our predictor is composite and can be used to assess spine age, hip age and knee age, in addition to general musculoskeletal aging. We find that accelerated musculoskeletal aging is moderately correlated between these different musculoskeletal dimensions (e.g hip vs. knee: Pearson correlation=.351+/-.004). Musculoskeletal aging is heritable at more than 35%, and the genetic factors are partially shared between joints (e.g hip vs. knee: genetic correlation=.52+/-.04). We identified single nucleotide polymorphisms associated with accelerated musculoskeletal aging in approximately ten genes for each musculoskeletal dimension. General musculoskeletal aging is for example associated with a TBX15 variant linked to Cousin syndrome and acromegaloid facial appearance syndrome. Finally, we identified biomarkers, clinical phenotypes, diseases, environmental and socioeconomic variables associated with accelerated musculoskeletal aging in each dimension. We conclude that, while the aging of the different components of the musculoskeletal system is connected, each bone and joint can age at significantly different rates.

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