Identification of Genetic Loci on Chromosome 4B for Improving the Grain Number per Spike in Pre-Breeding Lines of Wheat

The grain number per spike (GNPS) is an important yield component, and much attention is given to the increase in GNPS for current yield improvement of common wheat. Here, a panel of 259 pre-breeding lines and elite commercial varieties were collected for the investigation of 12 agronomic traits, especially for spike-related traits, with 2-year replicates. The high correlation between GNPS and kernel number per spikelet (KNS) suggested that the high GNPS trait in our pre-breeding lines was mainly controlled by grain set number per spikelet. Genome-wide association studies (GWAS) using the 660K SNP genotyping assay suggested that a major locus on chromosomes 4BS contributed to the high GNPS trait, which contributed to 33% and 48% of the variation in KNS and GNPS, respectively. A good diagnostic KASP marker AX-109286577 flanking the 4BS locus was developed for easy selection of the large spike trait. Taken together, the results suggested that untapped rare allele variation in our pre-breeding lines can be used for improvement of the yield component of set grain number per spike.

ADHD and DIRAS Single Nucleotide Polymorphism as an Indicator of Prolonged Concussion Recovery

The purpose of this study was to determine the association between the presence of a single nucleotide polymorphism (SNP; rs1412005) within DIRAS2 (i.e., a gene associated with attention-deficit/hyperactivity disorder (ADHD) and prolonged recovery following a sport-related concussion. A case-control study design was implemented, where cases and controls were selected from a cohort of 117 deidentified concussed athletes. Eleven samples from this patient cohort self-reported ADHD diagnosis and were age and sex-matched to 22 participants with no self-reported ADHD diagnoses. The average recovery times were 21.50 + 13.96 days and 15.66 + 8.50 days for the case and control groups, respectively. The authors found that only 13.6% of the individuals without an ADHD diagnosis recovered in > 30 days (p = 0.044). Also, the authors found that 72.7% of the carriers of the T allele (i.e., minor allele) recovered in greater than 30 days (p = 0.213). Researchers concluded that individuals with ADHD had a higher risk of prolonged concussion recovery lasting greater than 30 days. Also, carrying the rare allele was associated with prolonged recovery, which suggests this SNP could be a potential genetic marker for both prolonged concussion recovery and the presence of ADHD.

Sudden infant death syndrome revisited: serotonin transporter gene, polymorphisms and promoter methylation

Background Based on findings in the brain stems of SIDS victims, the serotonin transporter (5-HTT) gene has been discussed to be associated with SIDS. Methods In the largest study to date, we investigated the promoter length (5-HTTLPR) and intron 2 VNTR polymorphisms in 274 cases and 264 controls and the Ile425Val polymorphism in 65 cases and 64 controls. Moreover, the methylation of the internal promoter region was investigated in 35 cases and 14 controls. Results For 5-HTTLPR, we observed a trend towards an association of allele L (58.8% vs. 53.4%) with SIDS and significant results were observed after stratifying for age, season at death, and prone position. Nevertheless, when pooling all published data, a significant association of allele L with SIDS is confirmed (p: 0.001). For the intron 2 VNTR polymorphism, no significant differences were observed. After pooling, a significant accumulation of the rare allele 9 was observed in SIDS (2.1% vs. 0.6%; p: 0.018). For the Ile425Val polymorphism, no differences were observed. Conclusion We conclude that genetic variation at this gene might be of some importance in SIDS. Epigenetic analysis of the internal promoter, however, revealed no influence on the relative risk to succumb to SIDS. Impact This is the largest study published up to now on 5-HTT gene polymorphisms and SIDS. Polymorphisms in the 5-HTT gene appear to contribute (although to a small degree) to the risk to die from SIDS. There is no evidence that a methylation of the promoter region is of impact for the etiology of SIDS.

Association of SCN5A gene polymorphism with dilated cardiomyopathy

Subjects and methods. The study included patients with IDC (group 1; n=111, 89.2% men, average age 51.7±9.7 years) and ICM (group 2; n=110, 91.5% men, average age 58.7±8.4 years). All patients (IDC and ICM) underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the group 1. And those patients who were reliably diagnosed with coronary artery disease were in the group 2, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. The control group (n=121, average age 53.6±4.8 years) included patients who had no manifestations of cardiovascular diseases. The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs1805124).Results. In the group with IDC 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with IDC compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group of patients with ICM, the А allele (69.5% vs. 80.1%, p=0.003) and the AA genotype (50.9% vs. 63.3%, p=0.030) were significantly less common than in the control group. The rare homozygous GG genotype was statically more common in patients with ICM compared to the control group (11.8% vs. 3.2%, p=0.004). Also, the G allele in the group of patients with ICM was detected statically significantly more often than in the control group (30.5% vs. 19.9%, p= 0.003).Conclusion. The polymorphic locus rs1805124 of the SCN5A gene is associated with both IDC and ICM. Homozygous genotype AA and allele A are conditionally protective factors for the development of these conditions in men.

Early Elevation of Complement Factor Ba Is a Predictive Biomarker for Transplant-Associated Thrombotic Microangiopathy

Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous reports suggest that TA-TMA is caused by complement activation by complement-related genetic variants; however, this needs to be verified, especially in adults. Here, we performed a nested case-control study of allo-HSCT-treated adults at a single center. Fifteen TA-TMA patients and 15 non-TA-TMA patients, matched according to the propensity score, were enrolled. Based on a previous report showing an association between complement-related genes and development of TA-TMA, we first sequenced these 17 genes. Both cohorts harbored several genetic variants with rare allele frequencies; however, there was no difference in the percentage of patients in the TA-TMA and non-TA-TMA groups with the rare variants, or in the average number of rare variants per patient. Second, we measured plasma concentrations of complement proteins. Notably, levels of Ba protein on Day 7 following allo-HSCT were abnormally and significantly higher in TA-TMA than in non-TA-TMA cases, suggesting that complement activation via the alternative pathway contributes to TA-TMA. All other parameters, including soluble C5b-9, on Day 7 were similar between the groups. The levels of C3, C4, CH50, and complement factors H and I in the TA-TMA group after Day 28 were significantly lower than those in the non-TA-TMA group. Complement-related genetic variants did not predict TA-TMA development. By contrast, abnormally high levels of Ba on Day 7 did predict development of TA-TMA and non-relapse mortality. Thus, Ba levels on Day 7 after allo-HSCT are a sensitive and prognostic biomarker of TA-TMA.

Penetrance estimation of SORL1 loss-of-function variants using a family-based strategy adjusted on APOE genotypes suggest a non-monogenic inheritance

For complex disorders, estimating the age-related penetrance associated with rare variants of strong effect is essential before a putative use for genetic counseling or disease prevention. However, rarity and co-occurrence with other risk factors make such estimations difficult. In the context of Alzheimer disease, we present a survival model to estimate the penetrance of SORL1 rare (allele frequency <1%) Loss-of-Function variants (LoF) while accounting for APOE-ε4, the main risk factor (allele frequency ~14% in Caucasians). We developed an efficient strategy to compute penetrance estimates accounting for both common and rare genetic variants based on available penetrance curves associated with common risk factors and using incomplete pedigree data to quantify the additional risk conferred by rare variants. Our model combines: (i) a baseline for non-carriers of SORL1 LoF variants, stratified by APOE genotypes derived from the Rotterdam study and (ii) an age-dependent proportional hazard effect for SORL1 LoF variants estimated from pedigrees with a proband carrying such a variant. We embed this model into an Expectation-Maximisation algorithm to accommodate for missing genotypes. Confidence intervals were computed by bootstraps. To correct for ascertainment bias, proband phenotypes were omitted. We obtained penetrance curves associated with SORL1 LoF variants at the digenic level. By age 70, we estimate a 100% penetrance of SORL1 LoF variants only among APOE-ε4ε4 carriers, while penetrance is 56% [40%-72%] among ε4 heterozygous carriers and 37% [26%-51%] among ε4 non-carriers. We conclude that rare SORL1 LoF variants should not be used for genetic counseling regardless of the APOE status.

A novel nonlinear dimension reduction approach to infer population structure for low-coverage sequencing data

Background Low-depth sequencing allows researchers to increase sample size at the expense of lower accuracy. To incorporate uncertainties while maintaining statistical power, we introduce to analyze population structure of low-depth sequencing data. Results The method optimizes the choice of nonlinear transformations of dosages to maximize the Ky Fan norm of the covariance matrix. The transformation incorporates the uncertainty in calling between heterozygotes and the common homozygotes for loci having a rare allele and is more linear when both variants are common. Conclusions We apply to samples from two indigenous Siberian populations and reveal hidden population structure accurately using only a single chromosome. The package is available on https://github.com/yiwenstat/MCPCA_PopGen.

An investigation of the effects of <i>BMPR1B</i>, <i>BMP15</i>, and <i>GDF9</i> genes on litter size in Ramlıç and Dağlıç sheep

This study was carried out to determine the presence of polymorphisms in genes affecting litter size. The SNPs in bone morphogenetic protein receptor type 1B (BMPR1B), bone morphogenetic protein 15 (BMP15), and growth differentiation factor 9 (GDF9) genes were detected in 60 uniparous and 60 multiparous ewes from Ramlıç and Dağlıç breeds. The ewes are maintained in nine public herds at the breeding station of the Afyonkarahisar Sheep and Goats Breeders' Association and lambed in two consecutive breeding seasons. PCR and DNA sequencing analyses were conducted, and 36, 4, and 11 SNPs in Ramlıç and 40, 3, and 11 SNPs in Dağlıç were detected in BMPR1B, BMP15, and GDF9 genes, respectively. A total of 16 SNPs in Ramlıç and 10 SNPs in Dağlıç breeds for three genes were found to be significant (P<0.05). The resulting analyses showed that four SNPs (g.49496G>A, c.1658A>C, c.2037C>T, c.2053C>T) of the BMPR1B gene and one deletion mutation (c.28_30delCTT) in the BMP15 gene of the Ramlıç breed as well as five SNPs (c.1487C>A, c.2492C>T, c.2523G>A, c.2880A>G, and c.2763G>A) of the BMPR1B gene of the Dağlıç breed have significant positive regression coefficients in the desired direction of the rare allele. The observed mutations have potential to be used as genetic markers in the selection of prolific animals for both breeds.

A Unique Allele Variant at STR Locus D2S1338 in a Paternity Testing Case

Background: The relationship testing through DNA profiling may undesirably be affected by the rare allele variants, tri-allelic pattern and null alleles. Therefore, it is vital to report such anomalies. We report a paternity testing in a sexual assault case studied at Punjab Forensic Science Agency, Lahore Pakistan showing a unique allele variant in mother and child. Methods: DNA was extracted from the buccal swabs of reference samples using organic extraction method and DNA profiling was done for 15 autosomal STRs and amelogenin using Identifiler Plus kit. Results: A novel out of marker range (OMR) allele variant between STR Loci D16S539 and D2S1338 was observed in the DNA profiles of victim (mother) as well as the child. At STR locus D2S1338 Twenty one different allele variant are listed at STRBase ranging from 11 to 28. The allele variant observed in this case study was appeared at less than marker range (< D2S1338) with a size of 297.50 bp. The novel variant OMR allele at D2S1338 was labeled as allele 13, when compared to the other allele in allelic ladder. Moreover, the PFSA DNA database was searched for this unique allelic variation and it was found that this was present in only two other samples of distinct cases. Conclusion: The overall frequency of this unique allele variant was 3 in 10,125 unrelated individuals with frequency of occurrence of 0.0296. According to our limited knowledge it is the first report of a novel OMR allele variant at D2S1338 in Pakistani Population.

Association of ADRB2 gene polymorphism with dilated cardiomyopathy

Aim. To study the association of the rs1042713 polymorphism of the ADRB2 gene with cardiomyopathies of various origins. Material and methods. The study included patients with dilated cardiomyopathy (DCMP) and myocardial dilatation of ischemic genesis (DM IG).The total number of people surveyed is 221. The average age of the subjects was 55.309.69 years. Patients were divided into 2 groups: one of them patients with a diagnosis of dilated cardiomyopathy idiopathic (predictors of expansion of the heart cavities are excluded) and the other-patients with dilated myocardium of ischemic origin (a history of IHD). The number of patients in the first group was 111, including 99 (89.2%) men and 12 (10.8%) women. The average age of patients in this group is 51.739.74 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 (91.5%) men and 10 (8.5%) women. The average age of the respondents is 58.688.38 years. The control group consists of individuals who did not have any manifestations of cardiovascular diseases. Their number is 221 people (average age 53.64.8 years). Laboratory and instrumental studies, coronary angiography, and molecular genetic studies of the rs1042713 polymorphism of the ADRB2 gene were performed for all participants in the study. Those patients who were excluded predictors of the occurrence of dilation of the heart cavities were assigned to the first group. The second group included patients with a history of CHD. Results. In the group with DCMP, 10.8% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype 48.6%, and the rare homozygous GG genotype 40.5%. In the group of patients with DM IG, 16.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype 51.8%, and the rare homozygous GG genotype 31.8%. In the control group, 11.8% of patients were identified as carriers of the homozygous genotype for the common allele, 47.5% carriers of the heterozygous genotype, and 40.7% carriers of the homozygous genotype for the rare allele. No statistically significant results were obtained in the group of patients with DCMP and DM IG compared to the control group of the rs1042713 polymorphism of the ADRB2 gene. Conclusion. No association of ADRB2 gene rs1042713 polymorphism with DCMI and DM IG was revealed.