Exonic Single Nucleotide Polymorphisms Research Articles

Genetic analysis of antithrombin deficiency among Thai patients with thrombosis

Hereditary antithrombin (AT) deficiency, primarily caused by mutations of SERPINC1 mutations, is a strong risk factor for occurrences and recurrences of venous thrombosis. While AT activity level measurements may be interfered by several factors, genetic analysis is more definitive for diagnosis. This study aims to address the knowledge gap of genetic basis of AT deficiency among Thai patients. Samples were collected from patients with thrombosis and low AT activities. Cases with acquired causes of low AT were excluded. All 7 exons of the SERPINC1 gene were PCR amplified and subjected to Sanger sequencing. The study included 15 patients and 6 controls with normal AT activity levels. The results revealed the presence of 6 benign single nucleotide polymorphisms (SNPs) located in intron 1, 2, exon 5 and intron 5. Two of these SNPs in intron 2 were first described here. Notably, a novel SNP in exon 3, SERPINC1 c.570 C>G (p.Y190X), was discovered. This is likely pathogenic because the premature stop codon led to a non-functional protein. The results suggest that pathogenic SERPINC1 variants detectable by DNA sequencing are uncommon among Thai patients with low AT activity levels underscoring the role of genetic analysis for definitive diagnosis. Further studies involving larger numbers of patients are required.

8067 AVP Gene Mutation: A Rare Cause of Diabetes Insipidus

Abstract Disclosure: N. Navrange: None. M. Williams: None. P. Madhavan: None. Introduction: Arginine vasopressin deficiency (AVP-D), also known as neurohypophyseal or central diabetes insipidus (DI), is marked by a reduced secretion of arginine vasopressin (AVP), resulting in polyuria and polydipsia. AVP-D is a rare disorder, with a prevalence of 1 in 25,000. Typically, the disorder is acquired. However, in less than 5% of cases, it has a genetic etiology. The majority of mutations in the AVP gene are autosomal dominant. Normally, AVP encodes vasopressin, also known as antidiuretic hormone (ADH). It plays a key role in the reabsorption of water in the kidney, the regulation of blood pressure, and controlling the body’s osmotic balance. However, a mutation in this gene leads to a deficient release of ADH, leading to reduced reabsorption of water in the collecting duct and decreased ability to concentrate urine. This results in increased urine output and excessive thirst. The onset and severity of symptoms varies between individuals. Case Report: In this report, we discuss the case of a 40-year-old Caucasian female with familial neurohypophyseal diabetes insipidus. The patient presented to the clinic for follow-up care of DI and hyponatremia. She received her DI diagnosis before the age of 5 and has multiple family members with the condition including her maternal grandfather, mother, and 2 siblings. Additionally, she suspected one of her children was exhibiting excessive urination. Past medical history is also significant for seizure disorder, postpartum cardiomyopathy, Chiari malformation type I and remote history of substance abuse. Vitals were stable with blood pressure of 122/86 mmHg, heart rate of 93 bpm, body mass index of 31.8. Physical exam was unremarkable except for obesity. She is currently managed with DDAVP 0.05 mg twice daily. Previously, imaging was performed to rule out pituitary abnormalities. The patient was referred for genetic testing due to her family history and was found to have a previously described rare autosomal dominant mutation of the AVP protein. The single nucleotide polymorphism in exon 1 results in a missense mutation substituting an alanine nucleotide for threonine (c.55G>A). The patient was counseled to share these results with her children’s pediatrician, as they could benefit from testing for the mutation. Discussion: Our patient has a pathogenic variant in AVP, specifically a missense mutation from Alanine to Threonine at codon 19 of the AVP protein. This mutation is associated with autosomal dominant neurohypophyseal diabetes insipidus. This case provides an example of a rare cause of neurohypophyseal diabetes insipidus and emphasizes the necessity of obtaining detailed family history in patients who have DI and considering genetic testing for patients with suspicion for familial involvement. Presentation: 6/2/2024

Development and validation of a 5K low-density SNP chip for Hainan cattle

BackgroundThis study aimed to design and develop a 5K low-density liquid chip for Hainan cattle utilizing targeted capture sequencing technology. The chip incorporates a substantial number of functional single nucleotide polymorphism (SNP) loci derived from public literature, including SNP loci significantly associated with immunity, heat stress, meat quality, reproduction, and other traits. Additionally, SNPs located in the coding regions of immune-related genes from the Bovine Genome Variation Database (BGVD) and Hainan cattle-specific SNP loci were included.ResultsA total of 5,293 SNPs were selected, resulting in 9,837 DNA probes with a coverage rate of 85.69%, thereby creating a Hainan cattle-specific 5K Genotyping by Target Sequencing (GBTS) liquid chip. Evaluation with 152 cattle samples demonstrated excellent clustering performance and a detection rate ranging from 96.60 to 99.07%, with 94.5% of SNP sites exhibiting polymorphism. The chip achieved 100% gender coverage and displayed a heterozygosity rate between 14.20% and 29.65%, with a repeatability rate of 99.65–99.85%. Analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed the potential regulatory roles of exonic SNPs in immune response pathways.ConclusionThe development and validation of the 5K GBTS liquid chip for Hainan cattle represent a valuable tool for genome analysis and genetic diversity assessment. Furthermore, it facilitates breed identification, gender determination, and kinship analysis, providing a foundation for the efficient utilization and development of local cattle genetic resources.

Genetic variations in HsP90AA1 chaperone gene across diverse Indian native cattle (<i>Bos indicus</i>) breeds adapted to varied agroclimatic regions

Indian zebu cattle during their separate evolution from Bos taurus, have acquired certain changes in a set of genes that regulate the body temperature in response to heat stress. Heat shock proteins (HSPs), the abundant and ubiquitous molecular chaperones play essential role in many cellular biological processes, and are preferentially transcribed in response to heat stress. The objective of this study was to comparatively screen variants/ single nucleotide polymorphisms (SNPs) in the HSP90AA1 gene in cattle breeds, viz., Gir, Kankrej, Ladakhi, Nagori, Nimari, Ongole, Rathi and Sahiwal, adapted to different agroclimatic regions of India including the exotic breed Holstein Friesian and yak (Bos grunniens). Sanger sequencing was carried out in all the translatable exons of the gene. The analysis revealed 6 SNPs – 3 were located in exon 3, 1 SNP each in exon 4 and 6, and another SNP in exon 9. We also identified a novel SNP 2937 (G>T) nucleotide position of exon 9. Interestingly, 2 variants detected at position 1924 (A>G) of exon 3 and 2343 (T>C) of exon 6 with a frequency of 0.9 and 0.73, respectively, were found to be almost fixed in nearly all of the Indian native cattle breeds. These SNPs could potentially be utilized to undertake genotype-phenotype association studies for superior heat stress tolerance trait in Indian native cattle.

Molecular and functional in vivo characterisation of murine Dectin-1 isoforms.

Dectin-1 is a C-type lectin-receptor involved in sensing fungi by innate immune cells. Encoded by the Clec7a gene, Dectin-1 exists in two major splice isoforms, Dectin-1a and 1b, which differ in the presence of a membrane-proximal stalk domain. As reported previously, this domain determines degradative routes for Dectin-1a and 1b leading to the generation of a stable N-terminal fragment exclusively from Dectin-1a. Here, we narrow down the responsible part of the stalk and demonstrate the stabilisation of the Dectin-1a N-terminal fragment in tetraspanin-enriched microdomains. C57BL/6 and BALB/c mice show divergent Dectin-1 isoform expression patterns, which are caused by a single nucleotide polymorphism in exon 3 of the Clec7a gene, leading to a non-sense Dectin-1a mRNA in C57BL/6 mice. Using backcrossing, we generated mice with the C57BL/6 Clec7a allele on a BALB/c background and compared these to the parental strains. Expression of the C57BL/6 allele leads to the exclusive presence of the Dectin-1b protein. Furthermore, it was associated with higher Dectin-1 mRNA expression, but less Dectin-1 at the cell surface according to flow cytometry. In neutrophils, this altered ROS production induced by Dectin-1 model ligands, while cellular responses in macrophages and dendritic cells were not significantly influenced by the Dectin-1 isoform pattern.

Weak purifying selection in allelic diversity of the ADSL gene in indigenous and local chicken breeds and red junglefowl in Thailand

High levels of purine and uric acid, which are associated with health issues such as gout and cardiovascular disease, are found in the meat of fast-growing broiler chickens, which raises concerns about the quality of chicken meat and the health of the consumers who consume it. High genetic homogeneity and uniformity, particularly in genes involved in the synthesis of inosine monophosphate (IMP) and subsequent process of purine synthesis, which are associated with the meat quality, are exhibited in commercial broiler chickens owing to intensive inbreeding programs. Adenosine succinate lyase (ADSL) is a key enzyme involved in de novo purine biosynthetic pathway and its genetic polymorphisms affect IMP metabolism and purine content. In this study, we investigated the polymorphism of the ADSL gene in indigenous and local chicken breeds and red junglefowl in Thailand, using metabarcoding and genetic diversity analyses. Five alleles with 73 single nucleotide polymorphisms in exon 2, including missense and silent mutations, which may act on the synthesis efficiency of IMP and purine. Their protein structures revealed changes in amino acid composition that may affect ADSL enzyme activity. Weak purifying selection in these ADSL alleles was observed in the chicken population studied, implying that the variants have minor fitness impacts and a greater probability of fixation of beneficial mutations than strong purifying selection. A potential selective sweep was observed in Mae Hong Son chickens, whose purine content was lower than that in other breeds. This suggests a potential correlation between variations of the ADSL gene and reduced purine content and an impact of ADSL expression on the quality of chicken meat. However, further studies are required to validate its potential availability as a genetic marker for selecting useful traits that are beneficial to human health and well-being.

Exploring the role of apolipoprotein E gene promoter polymorphisms in susceptibility to normal-tension glaucoma in a Korean population

Glaucoma, particularly primary open-angle glaucoma (POAG), poses a significant global health concern. Distinguished by intraocular pressure (IOP), POAG encompasses high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). Apolipoprotein E (APOE) is a multifaceted protein with roles in lipid metabolism, neurobiology, and neurodegenerative diseases. However, controversies persist regarding the impact of APOE single-nucleotide polymorphisms (SNPs) on open-angle glaucoma and NTG. This study aimed to identify APOE-specific SNPs influencing NTG risk. A cohort of 178 patients with NTG recruited from Uijeongbu St. Mary’s Hospital and 32,858 individuals from the Korean Genome and Epidemiology Study (KoGES) cohort were included in the analysis. Genotype and haplotype analyses were performed on three promoter SNPs (rs449647, rs769446, and rs405509) and two exonic SNPs (rs429358 and rs7412) located on chromosome 19. Among the five SNPs, rs769446 genotypes exhibited significant differences between cases and controls. The minor allele C of rs769446 emerged as a protective factor against NTG. Furthermore, haplotype analysis of the five SNPs revealed that the A-T-G-T-T haplotype was a statistically significant risk factor for NTG. This study indicated an association between APOE promoter SNPs and NTG in the Korean population. Further studies are required to understand how APOE promoter SNPs contribute to NTG pathogenesis.

Lack of Association between LOXL1 Variants and Pigment Dispersion Syndrome/Pigmentary Glaucoma: A Meta-Analysis.

The phenotypic similarities between exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) and pigment dispersion syndrome (PDS)/pigmentary glaucoma (PG), particularly their association with material deposition in the eye's anterior segment, have prompted investigations into genetic commonalities. This study focuses on the LOXL1 gene, conducting a comprehensive meta-analysis of three candidate gene association studies. We analyzed three single nucleotide polymorphisms (SNPs) of LOXL1: rs1048661, rs3825942, and rs2165241. Our results reveal nominal significance for the exonic SNPs rs1048661 and rs3825942 (p ≤ 0.01), but show no significant association for the intronic SNP rs2165241 (p = 0.83) with PDS/PG. There was homogeneity across study cohorts (I2 = 0), and sensitivity analyses and funnel plots confirmed a lower likelihood of bias in our findings. The lack of a statistically significant association between LOXL1 variants and PDS/PG at p < 0.05 was attributable to the insufficient statistical power of the pooled data, which ranged from 5% to 37% for the three SNPs. This study suggests no association between LOXL1 variants and PDS/PG. Further validation and exploration of XFS/XFG-associated genes in larger and more diverse cohorts would be helpful to determine the genetic correlation or distinctiveness between these conditions.

Selecting autotetraploids from a facultatively apomictic tree of the nonapomictic ‘Licheng’ sweet orange (Citrus sinensis) variety

Tetraploid plays major roles in the polyploid breeding and production of citrus plants. Autotetraploids of nonapomictic citrus varieties are desirable in citrus polyploid breeding due to their high frequencies of hybrid polyploid production, certain genotypes and some predictable phenotypes. However, it is difficult to obtain autotetraploids of nonapomictic citrus varieties. In the present study, the nonapomictic sweet orange variety ‘Licheng’, which is native to China, was used as the main material. A ‘Licheng’ tree, LCOYC-04, that produced polyembryonic seeds at a frequency of 34.96±2.88 % was selected. Plants that grew from self-pollinated polyembryonic seeds of LCOYC-04 were investigated by flow cytometry. Four tetraploids were selected from 550 plants and identified according to chromosome observation. Exonic single-nucleotide polymorphism (SNP) locus genotyping based on genome resequencing showed that 22.18 %-70.49 % of heterozygous loci in the genome of LCOYC-04 were homozygous in the genomes of plants grown from self-pollinated monoembryonic seeds. The proportions of homozygous loci were 2.07 %-2.45 % in the 4 selected tetraploids. These values were close to those in 7 asexual ‘Licheng’ relatives (1.97 %-2.71 %). Therefore, the 4 tetraploids were confirmed to be autotetraploids of LCOYC-04. Genome sequencing revealed a region of low sequencing depth (approximately 855 kb) on chromosome 4 of all ‘Licheng’ trees. The CitRWP gene, which is responsible for the occurrence of nucellar embryos in citrus plants, was located in the low sequencing depth region. It was confirmed by quantitative PCR that one of two allelic CitRWP gene was defective in genome of ‘Licheng’. The current study indicates that it is possible to induce nonapomictic citrus to mutate into facultatively apomictic citrus through chromosome segment deletion, and provides a reference for excavating autotetraploids which produce polyembryonic and monoembryonic seeds.

Association Between AIRE Polymorphisms rs870881(C>T), rs1003854(T>C) and Rheumatoid Arthritis Risk: A Hungarian Case-control Study.

Autoimmune regulator (AIRE) is a transcription factor that plays pivotal role in controlling autoimmunity. In the thymus, it supports the presentation of peripheral tissue antigens to developing T cells, where recognition of these self-antigens negatively selects the autoimmune naïve T-cells by central tolerance. Studies demonstrated that single-nucleotide polymorphisms (SNPs) in AIRE alter transcription and propagate clonal survival of autoimmune T cells, therefore increase susceptibility to autoimmune diseases. This study intended to identify SNPs in exon and intron sequences that determine AIRE transcription, where their genotypes are associated with rheumatoid arthritis (RA) risk and clinical parameters. After a thorough in silico research, we enrolled 100 patients with RA and 100 healthy controls to analyze the association of SNP rs870881(C>T) and rs1003854(T>C) in AIRE coding sequence with RA risk by using five different genetic models and selected clinical parameters. Multiplex quantitative polymerase chain reaction was used to determine allelic discrimination of SNPs. RA risk was assessed by odds ratios (ORs) and confidence intervals (CIs). In a recessive model of rs878081, minor allele TT homozygotes were associated with RA (p=0.032, OR=5.44, 95%CI=1.16-25.52); in a recessive model of rs1003854, minor allele CC homozygotes were associated with RA (p=0.047, OR=4.84, 95%CI=1.02-23.02). Higher C-reactive protein (CRP) levels in patients with RA were significantly associated with minor allele homozygotes in recessive and codominant genetic models (p=0.029 and p=0.043, respectively) of rs1003854. Genotypes for minor alleles of rs878081 and rs1003854 might be involved in RA pathogenesis and risk prediction.

Variability in 2-acetyl-1-pyrroline production and associated mutations in BADH2 gene in aromatic rice cultivars of Bangladesh

Aroma is a special trait and aspect of the end-use quality of rice and its principal component is 2-acetyl-1-pyrroline (2AP). Sequence variants of betaine aldehyde dehydrogenase (BADH2) gene on rice chromosome 8 are associated with fragrance, and the most prominent mutation is an 8-bp deletion and three single nucleotide polymorphisms (SNPs) in exon 7. In this study, we analyzed sequence variations in exon 7 of BADH2 in four locally popular aromatic rice cultivars and six non-aromatic high-yielding rice varieties in Bangladesh. Sequencing and alignment analysis revealed that two aromatic rice cultivars, Kataribhog and Sakkorkhana, had an 8-bp deletion (discontinuous) and one SNP (A/T) in exon 7 of the BADH2 gene. However, deletions were absent in the other two aromatic rice cultivars (Chinigura and Ranisalut) and all high-yielding varieties (BRRI dhan28, BRRI dhan29, BRRI dhan86, BRRI dhan87, BRRI dhan92 and BINA dhan10). Gene expression analysis using specific markers also supports these findings. Our results suggest that aromaticity in local rice cultivars in Bangladesh may be regulated by differential genetic mechanisms. Further studies are needed to elucidate the genetic mechanisms and fragrant compound(s) involved in the fragrance traits of Chinigura, Ranisalut, and other locally cultivated aromatic rice varieties that are critical for the development of high-yield aromatic rice by knocking out the targeted gene(s) using CRISPR-Cas genome editing.

Natural allelic variation in the EamA-like transporter, CmSN, is associated with fruit skin netting in melon.

A SNP mutation in CmSN, encoding an EamA-like transporter, is responsible for fruit skin netting in melon. In maturing melon (Cucumis melo L.), the rind becomes reticulated or netted, a unique characteristic that dramatically changes the appearance of the fruit. However, little is known about the molecular basis of fruit skin netting formation in this important cucurbit crop. Here, we conducted map-based cloning of a skin netting (CmSN) locus using segregating populations derived from the cross between the smooth-fruit line H906 and the netted-fruit line H581. The results showed that CmSN was controlled by a single dominant gene and was primarily positioned on melon chromosome 2, within a physical interval of ~ 351kb. Further fine mapping in a large F2 population narrowed this region to a 71-kb region harboring 5 genes. MELO3C010288, which encodes a protein in the EamA-like transporter family, is the best possible candidate gene for the netted phenotype. Two nonsynonymous single nucleotide polymorphisms (SNPs) were identified in the third and sixth exons of the CmSN gene and co-segregated with the skin netting (SN) phenotype among the genetic population. A genome-wide association study (GWAS) determined that CmSN is probably a domestication gene under selective pressure during the subspecies C. melo subsp. melo differentiation. The SNP in the third exon of CmSN (the leading SNP in GWAS) revealed a bi-allelic diversity in natural accessions with SN traits. Our results lay a foundation for deciphering the molecular mechanism underlying the formation of fruit skin netting in melon, as well as provide a strategy for genetic improvement of netted fruit using a marker-assisted selection approach.

Application of genetic risk score for in-stent restenosis of second- and third-generation drug-eluting stents in geriatric patients

BackgroundThe second-and third-generation drug-eluting stents (DESs) in-stent restenosis (ISR) genetic risk score (GRS) model has been previously validated. However, the model has not been validated in geriatric patients. Therefore, we conducted this study to test the feasibility of the DES-ISR GRS model in geriatric patients with coronary artery disease (CAD) in Taiwan.MethodsWe conducted a retrospective, single-center cohort study and included geriatric patients (age ≥ 65 years) with CAD and second-or third-generation DES(s) deployment. Patients undergoing maintenance dialysis were excluded. ISR was defined as ≥ 50% luminal narrowing on the follow-up coronary arteriography. The DES-ISR GRS model included five selected exonic single-nucleotide polymorphisms (SNPs): CAMLG, GALNT2, C11orf84, THOC5, and SAMD11. The GRS was defined as the sum of the five selected SNPs for the risk allele.ResultsWe enrolled 298 geriatric patients from January 2010 and December 2019 in this study. After propensity score matching, there were 192 geriatric patients with CAD in the final analysis, of which 32 patients had ISR. Patients were divided into two groups based on their GRS values: low (0–2) and high (≥ 3) GRS. A high GRS was significantly associated with DES-ISR in geriatric patients.ConclusionThose geriatric patients with a high GRS had significantly higher second-or third-generation DES ISR rates. The five SNP-derived DES-ISR GRS model could provide genetic information for interventional cardiologists to treat geriatric patients with CAD.Trial registrationThe primary study protocol was registered with clinicaltrials.org. with registration number: NCT03877614; on March 15, 2019. (http://clinicaltrials.gov/ct2/show/NCT03877614)

Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants.

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the PKD1 gene (chrE3:g.42858112C>A, the conventional PKD1 variant). The aim of this study was to conduct a large-scale epidemiological study of ADPKD caused by the conventional PKD1 variant in Japan and to search for novel polymorphisms by targeted resequencing of the PKD1 using a next-generation sequencer. A total of 1281 cats visiting the Veterinary Medical Center of the University of Tokyo were included in this study. DNA was extracted from the blood of each cat. We established a novel TaqMan real-time PCR genotyping assay for the conventional PKD1 variant, and all cases were examined for the presence of this variant. Targeted resequencing of all exons of the PKD1 was performed on the DNA of 23 cats with the conventional PKD1 variant, six cats diagnosed with cystic kidneys but without this variant, and 61 wild-type normal cats. Among the 1281 cats examined in this study, 23 (1.8%) harboured the conventional PKD1 variant. The odds of having the conventional PKD1 variant were significantly higher in Persian cats, Scottish Folds and Exotic Shorthairs than in the other breeds, although the number of cases in each breed was small. Furthermore, we identified four variants unique to cats with cystic kidneys that were not found in wild-type normal cats, all of which were in exon 15. In particular, two (chrE:g.42848725delC, pGly1641fs and chrE:g.42850283C>T, pArg2162Trp) were candidate variants. This study revealed that the conventional PKD1 variant was prevalent in Scottish Fold, Persian and Exotic Shorthair breeds in Japan, and variants in exon 15 of PKD1, in addition to the conventional variant in exon 29, would be key factors in the pathogenesis of ADPKD in cats.

Significant association between a non-synonymous snp in IGFBP5 gene and the growth of striped catfish (Pangasianodon hypophthalmus, Sauvage, 1878)

Insulin-like growth factor binding protein 5 (IGFBP5) is the highest conserved member of IGFBP family, and has the broad range of biological activities effecting on the cell growth. This study aims to investigate the association between genetic variation in IGFBP5 gene and the growth of striped catfish (Pangasianodon hypophthalmus). Single nucleotide polymorphisms (SNPs) were discovered and validated in IGFBP5 gene from two growth-selected populations (fast- and slow- growing fish). For SNP discovery, the fragments of IGFBP5 from sample sets of 10 fast- growing fish and 10 slow- growing fish were directly sequenced by Sanger sequencing. In this stage, 4 exonic SNPs were discovered, including a non-synonymous SNP 525 T&gt;A (p. Val16Glu) in exon 1, and three synonymous SNPs (8859 G&gt;A, 11713 C&gt;A, 11992 T&gt;C) in exon 4. The non-synonymous SNP 525 T&gt;A (p.Val16Glu) was filtered to the next step of SNP validation. For validation, the SNP was individually genotyped in the test populations of 70 fast- growing fish and 70 slow- growing fish by single base extension method. Data analysis from the total SNPs which were collected from 80 fast- growing fish and 80 slow- growing fish indicated that non-synonymous SNP 525 T&gt;A (p.Val16Glu) was significantly associated to the growth of striped catfish (p-value &lt;0.001). Analysis of genetic diversity parameters (PIC, MAF) suggested that this SNP is a common variant, contributes significantly to the genetic variance. The non-synonymous SNP 525 T&gt;A (p.Val16Glu) in IGFBP5 gene would become a SNP marker candidate for marker assisted selection (MAS) that can be used in pangasius breeding.

UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10−7 (odds ratio = 1.72) and 1.1 × 10−7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.

Single-Nucleotide Polymorphisms Identified within Exon 2 of Fertility-Associated Bone Morphogenetic Protein (BMP15) Gene in Three Romanian Sheep Breeds

The improvement of the reproductive traits of animals is of great interest for livestock production. Due to its positive impact on the sheep industry’s profitability, prolificacy is one of the most economically significant biological traits, showing variation between and within breeds of domestic sheep (Ovis aries). Different mutations in BMPR-1B, BMP15 and GDF9 genes coding for the transforming growth factor-β (TGFβ) superfamily have been shown to influence the ovulation rate and litter size. Numerous single-nucleotide polymorphisms (SNPs) in the bone morphogenetic protein 15 (BMP15) gene have been linked to ewe fecundity. Using targeted PCR amplification and Sanger sequencing, we were able to identify heterozygous SNPs in exon 2 of BMP15 in three sheep breeds reared in Romania: Tsigai, Cluj Merino and Tsurcana. The sequence analysis revealed three previously documented mutations, namely the missense mutation c.755T&gt;C (L252P), which is predicted to change the tertiary structure of the BMP15 protein, and two silent mutations, c.747T&gt;C (P249P) and c.1047G&gt;A (V349V). In addition, we also identified one novel silent mutation, c.825G&gt;A (S275S). Based on our findings and publicly available data, we indicate four putative mutational hotspots within exon 2 of BMP15 that could be considered for improving the indigenous sheep breeds through targeted gene editing and SNP genotyping strategies.

Association of polymorphisms in exon 6 and 3′-untranslated region of the OLR1 gene with milk production traits in Sahiwal cattle

ABSTRACT The present investigation was undertaken to explain the association of SNPs (single nucleotide polymorphisms) in exon 6 and 3′-UTR of OLR 1 gene with milk traits in Sahiwal cattle. Milk traits were observed from 328 Sahiwal cows sired by 64 bulls viz: – First lactation 305 days milk yield (Kg) (FL305MY), Average test day milk yield (Kg) (ATDMY), Average test day fat percentage (%) (ATDFP) and Lactational fat yield (Kg) (LFY). The animal model was used to estimate the breeding values for FL305MY and LFY. The traits ATDMY and ATDFP were corrected for significant non-genetic factors by using LSML-Harvey and subsequently used for association studies. A total of 130 animals for PCR-RFLP and 103 for sequencing were screened through three sets of primers for the presence of polymorphisms in exon 6 and 3′-UTR of the OLR1 gene. The CC genotype of SNP C337A in the 3′-UTR of OLR1 gene had a significant effect (p < 0.01) on ATDFP and LFY. Allele combination CGC had a positive effect (p < 0.05) on ATDFP. Identified SNP C337A and CCGGCC haplotype can be used as potential markers for improving milk yield and composition traits in Sahiwal cattle.

Analysis Of The Association Between Sh2B1 chr16.28884655 And Type 2 Diabetes.

To determine correlation between genetic susceptibility of type 2 diabetes mellitus (T2DM) and Src homology 2 B adapter protein 1 (SH2B1) gene polymorphism in a diabetic population. Methods: A total of 111 T2DM patients (DM group) and 34 healthy controls (NC group) from Shanxi Provincial People's Hospital were included in this study. Exon 9 of the SH2B1 gene was detected using the Sanger sequencing method, and the relationship between SH2B1 gene polymorphism and diabetes was analyzed. Results: Comparison of the data between the two groups showed that the values of TG, the updated HOMA of insulin resistance (HOMA2-IR), weight, body mass index, waist circumference, fasting blood glucose and fasting insulin levels of the DM group were higher than those of the NC group (P < 0.05). The HOMA2 insulin sensitivity (%S) of the DM group was lower than that of the NC group (P < 0.05). Sequencing analysis revealed that the following five single nucleotide polymorphisms in exon 9 of SH2B1 may be related to T2DM: rs181578610, rs550079240, chr16.28884655, chr16.28884659 and chr16.28884831. Among them, chr16.28884655 was found to be significantly related to diabetes; this site, located on the NM_015503 exon, was related to TG, LDL-C and waist circumference. The SH2B1 gene locus chr16.28884655 was found to be significantly related to genetic susceptibility to T2DM.

NFκB1 Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in a Canadian Population.

Background: We examined associations between NFκB1 polymorphisms and influenza A (H1N1) clinical outcomes in Canadian. Methods: A total of thirty-six Caucasian patients admitted to the intensive care unit (ICU) in hospitals in Canada were recruited during the 2009 H1N1 pandemic. Genomic DNA was extracted from the whole blood samples. The NFkB1 gene was targeted for genotyping using next-generation sequencing technology—Roche 454. Results: A total of 136 single nucleotide polymorphisms (SNPs) were discovered within the NFκB1 gene. Among them, 63 SNPs were significantly enriched in patients admitted in the ICU (p < 0.05) compared with the British Caucasian population in the 1000 Genomes study. These enriched SNPs are mainly intron variants, and only two are exon SNPs from the non-transcribing portion of the NFκB1 gene. Conclusions: Genetic variations in the NFκB1 gene could influence clinical outcomes of pandemic H1N1 infections. Our findings showed that sequence variations of the NFκB1 gene might influence patient response to influenza infection.