FUT2 Research Articles

Genome-wide cross-trait analysis and Mendelian randomization reveal a shared genetic etiology and causality between COVID-19 and venous thromboembolism

Venous thromboembolism occurs in up to one-third of patients with COVID-19. Venous thromboembolism and COVID-19 may share a common genetic architecture, which has not been clarified. To fill this gap, we leverage summary-level genetic data from the latest COVID‐19 host genetics consortium and UK Biobank and examine the shared genetic etiology and causal relationship between COVID-19 and venous thromboembolism. The cross-trait and co-localization analyses identify 2, 3, and 4 shared loci between venous thromboembolism and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, which are mapped to ABO, ADAMTS13, FUT2 genes involved in coagulation functions. Enrichment analysis supports shared biological processes between COVID-19 and venous thromboembolism related to coagulation and immunity. Bi-directional Mendelian randomization suggests that venous thromboembolism was associated with higher risk of three COVID-19 traits, and SARS-CoV-2 infection was associated with a higher risk of venous thromboembolism. Our study provides timely evidence for the genetic etiology between COVID-19 and venous thromboembolism (VTE). Our findings contribute to the understanding of COVID-19 and VTE etiology and provide insights into the prevention and comorbidity management of COVID-19.

Human and pathogen genotype-by-genotype interactions in the light of coevolution theory.

Antagonistic coevolution (i.e., reciprocal adaptation and counter-adaptation) between hosts and pathogens has long been considered an important driver of genetic variation. However, direct evidence for this is still scarce, especially in vertebrates. The wealth of data on genetics of susceptibility to infectious disease in humans provides an important resource for understanding host-pathogen coevolution, but studies of humans are rarely framed in coevolutionary theory. Here, I review data from human host-pathogen systems to critically assess the evidence for a key assumption of models of host-pathogen coevolution-the presence of host genotype-by-pathogen genotype interactions (G×G). I also attempt to infer whether observed G×G fit best with "gene-for-gene" or "matching allele" models of coevolution. I find that there are several examples of G×G in humans (involving, e.g., ABO, HBB, FUT2, SLC11A1, and HLA genes) that fit assumptions of either gene-for-gene or matching allele models. This means that there is potential for coevolution to drive polymorphism also in humans (and presumably other vertebrates), but further studies are required to investigate how widespread this process is.

Extent of the protection afforded by histo-blood group polymorphism against rotavirus gastroenteritis in metropolitan France and French Guiana.

Human rotaviruses attach to histo-blood group antigens glycans and null alleles of the ABO, FUT2 and FUT3 genes seem to confer diminished risk of gastroenteritis. Yet, the true extent of this protection remains poorly quantified. Here, we conducted a prospective study to evaluate the risk of consulting at the hospital in non-vaccinated pediatric patients according to the ABO, FUT2 (secretor) and FUT3 (Lewis) polymorphisms, in Metropolitan France and French Guiana. At both locations, P genotypes were largely dominated by P [8]-3, with P [6] cases exclusively found in French Guiana. The FUT2 null (nonsecretor) and FUT3 null (Lewis negative) phenotypes conferred near full protection against severe gastroenteritis due to P [8]-3 strains (OR 0.03, 95% CI [0.00-0.21] and 0.1, 95% CI [0.01-0.43], respectively in Metropolitan France; OR 0.08, 95% CI [0.01-0.52] and 0.14, 95%CI [0.01-0.99], respectively in French Guiana). Blood group O also appeared protective in Metropolitan France (OR 0.38, 95% CI [0.23-0.62]), but not in French Guiana. The discrepancy between the two locations was explained by a recruitment at the hospital of less severe cases in French Guiana than in Metropolitan France. Considering the frequencies of the null ABO, Secretor and Lewis phenotypes, the data indicate that in a Western European population, 34% (95% CI [29%; 39%]) of infants are genetically protected against rotavirus gastroenteritis of sufficient severity to lead to hospital visit.

Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM

BackgroundOur previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC.MethodsIntestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC.ResultsThe expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2△IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2△IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM.ConclusionsThe regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.

Identification of two novel FUT1 mutations in people with Bombay phenotype from Iran

Background and purposeBombay and Para-Bombay phenotypes are characterized by FUT1 gene mutation and lack of H antigen expression in red blood cells. ABH antigens are not present in the body secretions of Bombay individuals, while they are expressed in the secretions of para-Bombay. The aim of this study was to investigate the molecular basis of FUT1 and FUT2 genes in Iranians with the Bombay or Para-Bombay phenotype. Materials and MethodsABO phenotype analysis and routine serological tests were performed on 11 people with Bombay and Para-Bombay phenotypes. The coding regions of FUT1 and FUT2 genes were amplified by PCR followed by sequencing. The ABO genotypes were also determined by sequencing exons 6 and 7 of the ABO gene. Results: Serological investigations confirmed the Bombay phenotype in 8 samples and the Para-Bombay phenotype in 3 samples. Family members with the Bombay phenotype had the classic c 0.725 T > G mutation in the FUT1 gene, accompanied by deletion of the FUT2 gene. Other samples had c.653 A>G, c 0.661 C>T, c 0.652 C>G, and c.722 A>C mutations in the FUT1 while FUT2 was silenced by c 0.461 G>A. Conclusion: In this research, we identified two novel mutations in the FUT1 gene in individuals with the Bombay phenotype. This and previous works confirm the variety of FUT1 mutations.

ABO discrepancy due to the para-Bombay phenotype: a case report

In this study, we aimed to determine and analyze the genetic differences of the FUT1 and FUT2 genes within an individual exhibiting the Para-Bombay phenotype. Standard serological tests were conducted to analyze the ABO phenotype. The amplification of FUT1 and FUT2 genes was conducted by polymerase chain reaction and amplicons were sequenced. The determination of the ABO genotype was conducted by sequencing exons 1 to 7 of the ABO gene. The Lewis phenotype was defined as Le(a−b+); Despite this, red blood cells (RBCs) did not show signs of A, B and H antigens using the serological method utilized in this study. However, Analyses of sequencing and cloning demonstrated the existence of a FUT1 mutation at position c.658C>T and an inactive allele FUT1*01N.06 (c.551_552delAG). Genetic testing for ABO blood types was subsequently determined to be ABO*B.01/ABO*B.01 (c.297A>G; c.526C>G; c.657C>T; c.703G>A; c.796C>A; c.803G>C; c.930G>A). Heterozygosity for indel and missense mutation within the coding region of FUT1 are likely to be responsible for development of the Para-Bombay phenotype.

Molecular Genetic Analysis of Para-Bombay Phenotype in Chinese: Identification of a Novel FUT1 Allele

The goal was to identify a novel FUT1 allele and to study serologic and gene feature of the para-Bombay blood type of one expectant mother in Xinjiang, China. ABO and Lewis groups were recognized by standard serologic techniques in an ABO typing discrepancy specimen from one person at the Tianjin Blood Center. DNA (deoxyribonucleic acid) was collected and polymerase chain reactions with sequence-specific primers (PCR-SSP) were performed to sequence exons 6 and 7 of ABO gene, exon 4 of FUT1 gene, and exon 2 of FUT2. PCR products were sequenced to identify ABO groups and the variation sites. The genotype was determined by family study. In our laboratory testing, erythrocytes from the proposita did not react with anti-A and anti-B reagents. B antigen was discovered only after adsorption and elution. Red cells were nonreactive with monoclonal anti-H. The sera of the proposita contained anti-A and were weakly agglutinated by B cells. The hybrid 902 A>G mutation was detected in the proposita's father and mother. The proposita has the same mutation 902 A>G, which was conjectured as homozygosity for 902 A>G. One novel mutation of FUT1 gene was observed in our laboratory. It has never been reported previously. The para-Bombay phenotype in the proposita originating from Xinjiang (China) results from homozygosity for FUT1 902 A>G, together with 357 C>T of FUT2.

GROWTH AND DEVELOPMENT OF PIGS WITH DIFFERENT GENOTYPES OF SLC11A1 AND FUT1 DNA MARKER

The article highlights the results of research of the growth and development characteristics of pigs with different genotypes of DNA markers of resistance to infectious diseases.
 The purpose of the study was to determine the effect of genes polymorphisms related to disease resistance on the growth and development of pigs and to assess the feasibility of using these markers in selection with the Large White breed. In order to achieve the goal, a number of tasks were solved: typing of SLC11A1 (NRAMP1) and FUT1 genes of the breeding herd of pigs of the inbred type UVB-3 (factory type "Bagachansky"); based on the results of typing, sub-experimental groups were formed and the growth and development of pigs of different genotypes were studied; an assessment of the influence of the specified DNA markers on absolute and relative growth, intensity of formation, tension and uniformity of growth of the experimental stock was carried out; the prospects of selection work based on the investigated DNA markers are determined.
 Material and methods. The research was carried out on purebred Large White pigs of the farm type "Bagachansky" of the farm "Plehiv-Agro" of the Poltava region. Genetic studies were carried out at the Institute of Pig Breeding and Agro-Industrial Production of the National Academy of Sciences. DNA typing was performed by the PCR-RFLP method. The live weight of experimental animals was determined monthly starting from weaning at 28 days until reaching the age of six months. Based on the results of weighing, average daily gain, absolute and relative growth, as well as indices of formation intensity, tension and uniformity of growth were calculated. Statistical processing of the obtained data was carried out using the Genalex 6 and Microsoft Excel 2019 programs.
 Results and conclusions. It was established that experimental pigs have a sufficiently high level of polymorphism for genetic markers SLC11A1/HinfI 334 C > T and FUT1 SNP g. 307 G > A to carry out an associative analysis. The Polymorphism Information Content index of according to these markers was equal to 0.350 and 0.320 units, respectively, which testifies to the value of the farm type "Bagachanskyi" for preserving the genetic diversity of pigs. It was established that the TT genotype of the DNA marker SLC11A1/HinfI 334 (associated with increased general resistance to infectious diseases) has a positive effect on the intensity of growth of pigs, as evidenced by higher growth after rearing and a 4.86% higher live weight at the age of 6 months (p < 0.05). The AA genotype of the DNA marker FUT1 g.307 G > A (associated with resistance to colibacteriosis) had a positive effect on the uniformity of growth of pigs, at the same time, the growth intensity of the influence of this marker was not detected, which indicates the feasibility of carrying out selection work on this gene to create a line pigs resistant to colibacteriosis. However, among animals with different FUT1 g.307 G > A genotypes, homozygotes with the G allele (susceptible to colibacteriosis) had the highest formation intensity, the difference was 12.19%. Probably, after weaning, piglets susceptible to the disease reduced growth rates after inoculation with opportunistic microorganisms, and after the completion of the infectious process, compensatory growth occurred. This assumption is consistent with the decrease in relative gains in piglets with genotype GG and AG in the period of 28–60 days and the increase in relative gains in these two groups in the period of 2–3 months. Whereas, in the group of piglets with the FUT1 AA genotype, the relative growth constantly decreased with age.
 Genotypes associated with better resistance to infectious diseases SLC11A1/HinfI 334 TT and FUT1 AA are characterized by lower intensity of formation and better uniformity of growth, which positively affected the fattening productivity and can be used in selection work. No negative impact of genotypes associated with increased resistance to infectious diseases (and in some cases a positive impact was established) on the growth and development of experimental pigs was found. Marker-associated selection based on the studied genes will contribute to the creation of new structural elements of a Large White breed of pigs with increased growth intensity and improved resistance to infectious diseases.

Novel blood-based FUT7 DNA methylation is associated with lung cancer: especially for lung squamous cell carcinoma

BackgroundThe death rate of lung cancer (LC) ranks first in the world. Changes of DNA methylation in peripheral blood may be related to malignant tumors. It is necessary to explore blood-based biomarkers of methylation to detect LC.MethodsMass spectrometry assays were conducted to measure DNA methylation levels of seven CpG sites within FUT7 gene in the peripheral blood of 428 patients with LC, 233 patients with benign pulmonary nodule (BPN) and 862 normal controls (NC). The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using per SD change and tertiles analyses by logistic regression. The predictive ability of the seven FUT7 CpG sites and risk factors were evaluated by receiver operating characteristic curve (ROC).ResultsThe methylation levels of seven CpG sites of FUT7 in LC were significantly lower than that in NC (P < 0.05). The per SD decrement of methylation level in CpG_1-7 was significantly associated with 65%, 38%, 59%, 46%, 23%, 20% and 68% higher risk for LC versus NC, respectively, and the adjusted ORs (95% CI) were 2.92 (2.17–3.96), 1.76 (1.29–2.38), 2.83 (2.09–3.82), 3.00 (2.17–4.16), 1.81 (1.35–2.43), 1.48 (1.11–1.97) and 3.04 (2.23–4.16) for the lowest tertiles of methylation level in CpG_1-7 compared with the top tertiles, respectively. The area under the curve (AUC) of FUT7_CpG_1-7 was 0.659 (CI 0.626–0.693), 0.792 (CI 0.736–0.848) and 0.729 (CI 0.665–0.792) in distinguishing LC versus NC, LUSC versus NC and LUSC versus BPN.ConclusionsOur study revealed an association between FUT7 hypomethylation and LC, especially for LUSC, which provides novel support for the blood-based methylation signatures as potential marker for assessing lung cancer risk.

Para-Bombay phenotype due to bi-allelic heterozygous base deletions of FUT1 gene

To explore the genetic mechanism underlying a case with para-Bombay phenotype. The ABO and Lewis phenotype were identified with serological methods. The coding regions of exons 6 and 7 of the ABO and FUT1 genes were amplified with PCR and directly sequenced. Haploid sequence analysis was carried out on the variant sites of the FUT1 gene. Serological analysis confirmed that the proband has a rare para-Bombay phenotype. Direct sequencing revealed that he was a B.01/O.01.02 heterozygote for the ABO gene, and had heterozygous deletion for the 768 and 881-882 sites of the FUT1 gene. Further haploid analysis showed that the c.881_882delTT deletion has occurred in one haploid while c.768delC was present in the other haploid. The proband was therefore determined as a FUT1*01N.13/01N.20 heterozygote, which have resulted in frameshift in polypeptide chain p.Phe294Cysfs*40 and p.Val257Phefs*23, respectively. A rare bi-allelic heterozygous deletion of para-Bombay phenotype has been identified in a blood donor. The c.881_882delTT and c.768delC deletions may decrease the activity of α-1,2-fucosyltransferase.

Primary sclerosing cholangitis-A long night's journey into day.

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Association analysis of DNA methylation and the tissue/developmental expression of the FUT3 gene in Meishan pigs

Porcine α-1,3-fucosyltransferase (FUT3), as a member of the fucosyltransferase family, plays an important role in the resistance of the piglet intestine to pathogenic microbial infection. To further investigate the tissue/developmental expression of FUT3 and its regulatory mechanism, we analyzed changes in the expression of FUT3 in the duodenal tissues of Meishan pigs at different ages and found that the expression of FUT3 showed a decreasing trend with increasing age. In addition, bisulfite sequencing identified nine methylated CpG sites in the FUT3 core promoter (−500 ∼ −206) region. Therein, the methylation level at the mC-9 site located in FUT3 showed a significantly negative association with mRNA expression (P < 0.05). A further dual-luciferase assay demonstrated that methylation at the mC-9 site of the FUT3 promoter inhibited its transcriptional activity. Then, we confirmed the binding of Sp1 to the FUT3 promoter using RNA knockdown and a ChIP-qPCR assay. Our findings indicate that DNA methylation at the mC-9 site may inhibit the binding of the transcription factor Sp1, thus regulating the developmental expression of the FUT3 gene in the duodenum, providing some theoretical basis for the FUT3 gene as an important candidate marker of disease resistance in Meishan pigs.

Genotyping of the rare Para-Bombay blood group in southern Thailand

IntroductionThe para-Bombay phenotype, or H-deficient secretor, results from different mutations of the FUT1, with or without the FUT2 mutation. Consequently, there is an absent or weak expression of the H antigen on red blood cells (RBCs). Routine ABO blood grouping for two siblings with blood group O showed discrepant results with their parental blood group AB. Fragments encompassing the entire coding region of the FUT1 and FUT2 genes were investigated. MethodsBlood and saliva specimens were collected to verify the correct ABO grouping by cell grouping, serum grouping and the hemagglutination inhibition (HI) test, respectively. The FUT1 and FUT2 genomes were identified using the whole-exome sequencing (WES) in two children's DNA blood specimens and may have caused, or been relative to, their blood group. Genetic variations of the FUT1 and FUT2 genes have been investigated in the other family members using the Sanger sequencing. ResultsThe serologic reaction results of the proband revealed that A, B and H antigens were absent on RBCs, and that the serum contained anti-H. However, ABH and AH antigens were present in the saliva PB1 and PB2, respectively. The probands PB1 and PB2 were assigned as AB and A blood groups, respectively. Blood genotyping confirmed that heterozygous mutations of the FUT1 gene, c.551_552delAG, were identified. Three family members, PB3, PB, and PB8, also showed normal ABO blood groups, but their genotypes were also the FUT1 mutation c.551_552delAG. ConclusionsThe FUT1 mutation c.551_552delAG may result in the reduced or absent H antigen production on RBCs, which characterizes the para-Bombay phenotypes. Blood genotyping is essential if these individuals need a blood transfusion or are planning to donate blood.

Effect of the variant rs602662 of FUT2 gene on anthropometric and metabolic parameters in a Caucasian obese population.

Some obese subjects with genetic variants of FUT2 gene could be implied in metabolic disorders. The aim of the present investigation was to evaluate the association between SNP rs602662 in FUT2 gene with different obesity markers. 166 Caucasian obese subjects were enrolled. Anthropometric parameters, blood pressure, fasting blood glucose, insulin concentration, insulin resistance (HOMA-IR), lipid profile, C reactive protein and prevalence of metabolic syndrome were recorded. The genotype of FUT2 gene polymorphism (rs602662) was evaluated. The genotype distribution of the rs602662 variant was the following: 29.5% (n=49) (GG), 47.6% (n=79) (GA) and 22.9% (n=38) (AA). We observed statistical differences between both genotypes (GG+GA vs. AA) in BMI (Delta: 0.4±0.01 kg/m2: p=0.04), fat mass (Delta: 3.7±0.3 kg: p=0.02), body weight (Delta: 5.9±0.4 kg: p=0.02), waist circumference (Delta: 7.3+0.9 cm: p=0.03), glucose (Delta: 5.5±0.4 mg/dl: p=0.04), triglycerides (Delta: 25.9±1.4 mg/dl: p=0.01), HDL-cholesterol (Delta: -5.7±1.2 mg/dl: p=0.02), insulin (Delta: 5.0±0.9 mUI/L: p=0.02) and HOMA-IR (Delta: 1.4±0.1 units: p=0.03) levels. Percentages of metabolic syndrome, central obesity, hypertriglyceridemia, low HDL cholesterol and hyperglycemia were lower in AA obese subjects than GG+GA. Logistic regression analysis showed a decreased risk of metabolic syndrome in AA subjects (OR=0.28, 95% CI=0.11-0.71, p=0.01). AA genotype of FUT2 rs602662 is associated with lower BMI and a better metabolic profile than subjects with GG+GA genotypes.

Intestinal Norovirus Binding Patterns in Nonsecretor Individuals.

Human norovirus (HuNoV) infection is associated with an active FUT2 gene, which characterizes the secretor phenotype. However, nonsecretor individuals are also affected by HuNoV infection although in a lesser proportion. Here, we studied GII.3, GII.4, and GII.17 HuNoV interactions in nonsecretor individuals using virus-like particles (VLPs). Only GII.4 HuNoV specifically interacted with nonsecretor saliva. Competition experiments using histo-blood group antigen (HBGA)-specific monoclonal antibodies (MAbs) demonstrate that GII.4 VLPs recognized the Lewis a (Lea) antigen. We also analyzed HuNoV VLP interactions on duodenum tissue blocks from healthy nonsecretor individuals. VLP binding was observed for the three HuNoV genotypes in 10 of the 13 individuals, and competition experiments demonstrated that VLP recognition was driven by an interaction with the Lea antigen. In 3 individuals, binding was restricted to either GII.4 alone or GII.3 and GII.17. Finally, we performed a VLP binding assay on proximal and distal colon tissue blocks from a nonsecretor patient with Crohn's disease. VLP binding to inflammatory tissues was genotype specific since GII.4 and GII.17 VLPs were able to interact with regenerative mucosa, whereas GII.3 VLP was not. The binding of GII.4 and GII.17 HuNoV VLPs was linked to Lea in regenerative mucosae from the proximal and distal colon. Overall, our data clearly showed that Lea has a pivotal role in the recognition of HuNoV in nonsecretors. We also showed that Lea is expressed in inflammatory/regenerative tissues and interacts with HuNoV in a nonsecretor individual. The physiological and immunological consequences of such interactions in nonsecretors have yet to be elucidated. IMPORTANCE Human norovirus (HuNoV) is the main etiological agent of viral gastroenteritis in all age classes. HuNoV infection affects mainly secretor individuals where ABO(H) and Lewis histo-blood group antigens (HBGAs) are present in the small intestine. Nonsecretor individuals, who only express Lewis (Le) antigens, are less susceptible to HuNoV infection. Here, we studied the interaction of common HuNoV genotypes (GII.3, GII.4, and GII.17) in nonsecretor individuals using synthetic viral particles. Saliva binding assays showed that only GII.4 interacted with nonsecretor saliva via the Lewis a (Lea) antigen Surprisingly, the three genotypes interacted with nonsecretor enterocytes via the Lea antigen on duodenal tissue blocks, which were more relevant for HuNoV/HBGA studies. The Lea antigen also played a pivotal role in the recognition of GII.4 and GII.17 particles by inflammatory colon tissue from a nonsecretor Crohn's disease patient. The implications of HuNoV binding in nonsecretors remain to be elucidated in physiological and pathological conditions encountered in other intestinal diseases.

Common and unique features of glycosylation and glycosyltransferases in African trypanosomes.

Eukaryotic protein glycosylation is mediated by glycosyl- and oligosaccharyl-transferases. Here, we describe how African trypanosomes exhibit both evolutionary conservation and significant divergence compared with other eukaryotes in how they synthesise their glycoproteins. The kinetoplastid parasites have conserved components of the dolichol-cycle and oligosaccharyltransferases (OSTs) of protein N-glycosylation, and of glycosylphosphatidylinositol (GPI) anchor biosynthesis and transfer to protein. However, some components are missing, and they process and decorate their N-glycans and GPI anchors in unique ways. To do so, they appear to have evolved a distinct and functionally flexible glycosyltransferases (GT) family, the GT67 family, from an ancestral eukaryotic β3GT gene. The expansion and/or loss of GT67 genes appears to be dependent on parasite biology. Some appear to correlate with the obligate passage of parasites through an insect vector, suggesting they were acquired through GT67 gene expansion to assist insect vector (tsetse fly) colonisation. Others appear to have been lost in species that subsequently adopted contaminative transmission. We also highlight the recent discovery of a novel and essential GT11 family of kinetoplastid parasite fucosyltransferases that are uniquely localised to the mitochondria of Trypanosoma brucei and Leishmania major. The origins of these kinetoplastid FUT1 genes, and additional putative mitochondrial GT genes, are discussed.

Analysis of the molecular mechanism and pedigree investigation of para-Bombay phenotype caused by combined mutations at position h649 and h768 of FUT1 gene.

The para-Bombay phenotype is a rare red blood cell phenotype characterised by the lack of ABH antigens on red blood cells, but ABH substances can be found in saliva. The aim of this research was to study the mechanism of mutation of FUT1 and FUT2 genes and the pedigree of a family with the para-Bombay phenotype. The blood group was detected by a conventional serological method, H antigen adsorption-elution test, and testing saliva for A, B, and H antigens. We amplified and sequenced the ABO, FUT1, and FUT2 genes of the proband and her family using a polymerase chain reaction method, and performed TA cloning and sequencing on the amplified products of the FUT1 gene to determine its genotype. With the conventional serological method, it was found that the red blood cell phenotype of the proband and her sister lacked H antigen, while the adsorption-elution test of H antigen could detect weak H antigen. Through FUT1 cloning and sequencing, it was found that the proband had a compound heterozygous mutation of c.649G>T and c.768delC, and the genotype was FUT1*01W.24/FUT1*01N.20; the proband's father and mother had heterozygous mutations of c.768delC and c.649G>T, and their genotypes were FUT1*01N.20/FUT1*01 and FUT1*01W.24/FUT1*01. The sister's FUT1 mutation site and genotype were the same as the those of the proband. FUT2 gene sequencing revealed that the proband and sister had a synonymous mutation of c.357C>T, while their parents both had a synonymous mutation of c.357C>T and a missense mutation of c.385A>T. The Lewis blood types of the four samples all showed Le (a-b+), all of which were secretory. Blood group serology and molecular diagnostic techniques showed that the compound heterozygous mutations of the proband and her sister were inherited from their father and mother.

Association of Fut1 and Slc11a1 gene polymorphisms with productivity traits of Large White pigs

The purpose of our work was to study the polymorphism of genes associated with disease resistance and to search for their associations with productive traits in the population of the Ukrainian Large White pigs. For this study, 50 pigs were used, observations and measurements were carried out at the age from birth to 180 days. Genetic studies were carried out in a certified laboratory of the Institute of Pig Breeding and Agroindustrial Production. In the study of fucosyltransferase 1 and solute carrier family 11 member 1 genes, polymorphism was found in three of the five analyzed loci. In the Ukrainian Large White subpopulation of pigs the informativeness of these gene polymorphisms was at the optimal level for associative analysis, Polymorphism Information Content was greater than 0.3 in two loci. A sufficiently high level of Polymorphism Information Content indicates the value of this breed to preserve the biodiversity of pigs. The distribution of genotypes at some loci of the solute carrier family 11 member 1 gene was characterized by a deviation from the theoretically expected one due to the increase in the frequency of the heterozygous genotype. There was also a statistically confirmed deviation of the genotypes’ distribution from the normal and polymorphism fucosyltransferase 1 gene, but in this case in the direction of increasing the frequency of both homozygous variants. These results indicate the presence of a certain selection pressure on the mentioned polymorphisms and their possible impact on productive traits. The influence of solute carrier family 11 member 1 gene polymorphism on the weight of pigs at the age of 120 and 180 days, the average daily gain recorded in the period 28–120 days and from birth to 180 days, as well as on the backfat thickness, was established. The preferred genotype is TT, which can be used in breeding to obtain more productive animals with increased disease resistance, but in the selection of animals at this locus, it is necessary to control the backfat thickness and prevent breeding of pigs that may worsen this trait.

Fucosyltransferase 2: A Genetic Risk Factor for Intestinal Diseases.

The fucosyltransferase 2 gene (FUT2) mediates the synthesis of histoblood group antigens (HBGA) that occur in vivo from multiple organs, particularly on the surface of intestinal epithelial cells and body fluids. To date, many studies have demonstrated that the interaction of HBGA with the host microbiota is the cause of pathogenesis of intestinal diseases, making FUT2 non-secretor a risk factor for inflammatory bowel disease (IBD) due to the lack of HBGA. As HBGA also acts as an attachment site for norovirus (NoV) and rotavirus (RV), the non-secretor becomes a protective factor for both viral infections. In addition, the interaction of norovirus and rotavirus with symbiotic bacteria has been found to play an important role in regulating enteroviral infection in IBD. Given the current incomplete understanding of the complex phenomenon and the underlying pathogenesis of intestinal diseases such as IBD, it has recently been hypothesized that the FUT2 gene regulates intestinal bacteria through attachment sites, may help to unravel the role of FUT2 and intestinal flora in the mechanism of intestinal diseases in the future, and provide new ideas for the prevention and treatment of intestinal diseases through more in-depth studies.

Prediction of various blood group systems using Korean whole-genome sequencing data.

AimsThis study established blood group analysis methods using whole-genome sequencing (WGS) data and conducted blood group analyses to determine the domestic allele frequency using public data from the Korean whole sequence analysis of the Korean Reference Genome Project conducted by the Korea Disease Control and Prevention Agency (KDCA).Materials and methodsWe analyzed the differences between the human reference sequences (hg19) and the conventional reference cDNA sequences of blood group genes using the Clustal Omega website, and established blood group analysis methods using WGS data for 41 genes, including 39 blood group genes involved in 36 blood group antigens, as well as the GATA1 and KLF1 genes, which are erythrocyte-specific transcription factor genes. Using CLC genomics Workbench 11.0 (Qiagen, Aarhus, Denmark), variant analysis was performed on these 41 genes in 250 Korean WGS data sets, and each blood group’s genotype was predicted. The frequencies for major alleles were also investigated and compared with data from the Korean rare blood program (KRBP) and the Erythrogene database (East Asian and all races).ResultsAmong the 41 blood group-related genes, hg19 showed variants in the following genes compared to the conventional reference cDNA: GYPA, RHD, RHCE, FUT3, ACKR1, SLC14A1, ART4, CR1, and GCNT2. Among 250 WGS data sets from the Korean Reference Genome Project, 70.6 variants were analyzed in 205 samples; 45 data samples were excluded due to having no variants. In particular, the FUT3, GNCT2, B3GALNT1, CR1, and ACHE genes contained numerous variants, with averages of 21.1, 13.9, 13.4, 9.6, and 7.0, respectively. Except for some blood groups, such as ABO and Lewis, for which it was difficult to predict the alleles using only WGS data, most alleles were successfully predicted in most blood groups. A comparison of allele frequencies showed no significant differences compared to the KRBP data, but there were differences compared to the Erythrogene data for the Lutheran, Kell, Duffy, Yt, Scianna, Landsteiner-Wiener, and Cromer blood group systems. Numerous minor blood group systems that were not available in the KRBP data were also included in this study.ConclusionsWe successfully established and performed blood group analysis using Korean public WGS data. It is expected that blood group analysis using WGS data will be performed more frequently in the future and will contribute to domestic data on blood group allele frequency and eventually the supply of safe blood products.