FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility

Introduction and ObjectivesAbout 30-75% of infertile men are diagnosed with idiopathic infertility, thereby lacking major causative factors to explain their impaired fertility status. In this study, we used a large cohort of idiopathic infertile men to determine whether subgroups could be identified by an unbiased clustering approach and whether underlying etiologic factors could be delineated.Patients and MethodsFrom our in-house database Androbase®, we retrospectively selected patients (from 2008 to 2018) with idiopathic male infertility (azoo- to normozoospermia) who fit the following selection criteria: FSH ≥ 1 IU/l, testosterone ≥ 8 nmol/l, ejaculate volume ≥ 1.5 ml. Patients with genetic abnormalities or partners with female factors were excluded.For the identified study population (n=2742), we used common andrologic features (somatic, semen and hormonal parameters, including the FSHB c.-211G>T (rs10835638) single nucleotide polymorphism) for subsequent analyses. Cluster analyses were performed for the entire study population and for two sub-cohorts, which were separated by total sperm count (TSC) thresholds: Cohort A (TSC ≥ 1 mill/ejac; n=2422) and Cohort B (TSC < 1 mill/ejac; n=320). For clustering, the partitioning around medoids method was employed, and the quality was evaluated by average silhouette width.ResultsThe applied cluster approach for the whole study population yielded two separate clusters, which showed significantly different distributions in bi-testicular volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G>T (100%), while Cluster 2 contained most patients carrying a T allele (>96.6%). In the analyses of sub-cohorts A/B, two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were bi-testicular volume, FSH and FSHB c.-211G>T.ConclusionWith this first unbiased approach for revealing putative subgroups within a heterogenous group of idiopathic infertile men, we did indeed identify distinct patient clusters. Surprisingly, across all diverse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G>T, FSH, and bi-testicular volume. Further, Cohorts A and B were significantly separated by FSHB genotype (wildtype vs. T-allele carriers), which supports the notion of a contributing genetic factor. Consequently, FSHB genotyping should be implemented as diagnostic routine in patients with idiopathic infertility.

Study of Genetic Diversity for Selected Genotypes in Rice

The present investigation was undertaken to study the 54 rice genotypes to estimate the diversity, among selected rice genotypes for yield and its component characters. The experiment was carried out during Kharif, 2020, in a randomized block design with three replications at the Indian Institute of Rice Research, Rajendranagar, Hyderabad voluntary center (Kampasagar), in Telangana State. The data was collected on characters viz and salt-tolerant score 0-9 scale. The 54 genotypes of rice were grouped into twelve clusters. Clusters with their genotypes are presented in. Cluster I had 15 genotypes, Cluster II had 13 genotypes, whereas Cluster III had 4 genotypes Cluster IV, V had 4 genotypes and cluster VI had 6 genotypes cluster VII had 1 genotype cluster VIII had three genotypes cluster Ⅸ, Ⅹ, Ⅺ had 1 genotypes cluster Ⅻ had 3 genotypes Highest inter-cluster distance was exhibited between clusters VIII and Ⅺ. and lowest cluster divergence found between the clusters Ⅳ and VII Greater the distance, wider the genetic diversity among the genotypes of those clusters. For high heterotic recombinants performing genotypes would be used as parents in the recombination breeding program.

Universal Genotyping for Tuberculosis Prevention Programs: a 5-Year Comparison with On-Request Genotyping

ABSTRACTProspective universal genotyping of tuberculosis (TB) isolates is used by many laboratories to detect clusters of cases and inform contact investigations. Prior to universal genotyping, most TB prevention programs genotyped isolates on request only, relying on requests from public health professionals whose knowledge of a patient's clinical, demographic, and epidemiological characteristics suggested potential transmission. To justify the switch from on-request to universal genotyping—particularly in the public health domain, with its limited resources and competing priorities—it is important to demonstrate the additional benefit provided by a universal genotyping program. We compared the clustering patterns revealed by retrospective 24-locus mycobacterial interspersed repetitive unit–variable-number tandem repeat genotyping of all culture-positive isolates over a 5-year period to the patterns previously established by our genotyping-on-request program in the low-incidence setting of British Columbia, Canada. We found that 23.8% of isolates were requested during the study period, and while requested isolates had increased odds of belonging to a genotype cluster (adjusted odds ratio, 2.3; 95% confidence interval, 1.5 to 3.3), only 54.6% clustered with the requested comparator strain. Universal genotyping revealed 94 clusters ranging in size from 2 to 53 isolates (mean = 5) and involving 432 individuals. On-request genotyping missed 54 (57.4%) of these clusters and 130 (30.1%) clustered individuals. Our results underscore that TB patient networks are complex, with unrecognized linkages between patients, and a prospective province-wide universal genotyping program provides an informative, bias-free tool to explore transmission to a degree not possible with on-request genotyping.

Genome-based transmission modeling separates imported tuberculosis from recent transmission within an immigrant population

BackgroundIn many countries tuberculosis incidence is low and largely shaped by immigrant populations from high-burden countries. This is the case in Norway, where more than 80 per cent of TB cases are found among immigrants from high-incidence countries. A variable latent period, low rates of evolution and structured social networks make separating import from within-border transmission a major conundrum to TB-control efforts in many low-incidence countries.MethodsClinical Mycobacterium tuberculosis isolates belonging to an unusually large genotype cluster associated with people born in the Horn of Africa, have been identified in Norway over the last two decades. We applied modeled transmission based on whole-genome sequence data to estimate infection times for individual patients. By contrasting these estimates with time of arrival in Norway, we estimate on a case-by-case basis whether patients were likely to have been infected before or after arrival.ResultsIndependent import was responsible for the majority of cases, but we estimate that about a quarter of the patients had contracted TB in Norway.ConclusionsThis study illuminates the transmission dynamics within an immigrant community. Our approach is broadly applicable to many settings where TB control programs can benefit from understanding when and where patients acquired tuberculosis.

Genotype Cluster Analysis in PathogenicEscherichia coliIsolates Producing Different CDT Types

Diarrheagenic and uropathogenicE. colitypes are mainly characterized by the expression of distinctive bacterial virulent factors.stx1,stx2(Shiga toxins), andcdt(cytolethal distending toxin) genes have been acquired by horizontal gene transfer. Some virulent genes such asespP(serine protease),etpD(part of secretion pathway), andkatP(catalase-peroxidase), orsfpAgene (Sfp fimbriae), are on plasmids and the others likefliC(flagellin) and thefimHgene (fimbriae type-I) are located on chromosome. Genomic pathogenicity islands (PAIs) carry some virulent genes such ashlygene. To determine the existence of virulence genes incdtclinical isolates, genes includingstx1,stx2,cdt,hly,espP,katP,sfpA,etpD,fliC, andfimHwere assessed by Polymerase Chain Reaction (PCR). The most prevalent isolates foretpDandkatPgenes were 85.7% incdtII.katPgene was also observed 83.3% incdtI. However, in 42.85% ofcdtIIIisolates,espPgene was the most detected. Moreover,hlygene was also the most prominent gene incdtIII(71.42%).sfpA genewas observed in 66.6% ofcdtV.stx1gene was detected in 100% ofcdtII,cdtIV, andcdtVtypes. Presence and pattern of virulence genes were considered amongcdtpositive isotypes and used for their clustering and profiling.