Mouse Anti Human Fbln2 Hybridoma [DQUD-Gcmo3-2E9]

Mammalian gonadal sex-determining (GSD) genes are expressed in a unique population of somatic cells that differentiate into granulosa cells in XX gonads or Sertoli cells in XY gonads. The ability to efficiently isolate these somatic support cells (SSCs) during the earliest stages of gonad development would facilitate identifying 1) new candidate GSD genes that may be involved in cases of unexplained abnormal gonad development and 2) genes involved in the earliest stages of granulosa and Sertoli cell differentiation. We report the development of a unique mouse carrying two transgenes that allow XX and XY mice to be distinguished as early as Embryonic Day 11.5 (E11.5) and allow SSCs to be isolated from undifferentiated (E11.5) and early differentiated (E12.5) fetal gonads. The Mouse Genome 430v2.0 GeneChip (Affymetrix) was used to identify transcripts exhibiting a sexual dimorphic expression pattern in XX and XY isolated SSCs. The analysis revealed previously unidentified sexually dimorphic transcripts, including low-level expressed genes such as Sry, a gene not identified in other microarray studies. Multigene real-time PCR analysis of 57 genes verified that 53 were expressed in fetal gonads in a sexually dimorphic pattern, and whole-mount in situ hybridization analysis verified 4930563E18Rik, Pld1, and Sprr2d are expressed in XX gonads, and Fbln2, Ppargc1a, and Scrn1 are expressed in XY gonads. Taken together, the data provide a comprehensive resource for the spatial-temporal expression pattern of genes that are part of the genetic network underlying the early stages of mammalian fetal gonadal development, including the development of granulosa and Sertoli cells.

ObjectiveTo investigate to what extent low-frequency genetic variants (with minor allele frequencies <5%) affect the risk of intracranial aneurysms (IAs).MethodsOne thousand fifty-six patients with IA and 2,097 population-based controls from the Netherlands were genotyped with the Illumina HumanExome BeadChip. After quality control (QC) of samples and single nucleotide variants (SNVs), we conducted a single variant analysis using the Fisher exact test. We also performed the variable threshold (VT) test and the sequence kernel association test (SKAT) at different minor allele count (MAC) thresholds of >5 and >0 to test the hypothesis that multiple variants within the same gene are associated with IA risk. Significant results were tested in a replication cohort of 425 patients with IA and 311 controls, and results of the 2 cohorts were combined in a meta-analysis.ResultsAfter QC, 995 patients with IA and 2,080 controls remained for further analysis. The single variant analysis comprising 46,534 SNVs did not identify significant loci at the genome-wide level. The gene-based tests showed a statistically significant association for fibulin 2 (FBLN2) (best p = 1 x 10(-6) for the VT test, MAC >5). Associations were not statistically significant in the independent but smaller replication cohort (p > 0.57) but became slightly stronger in a meta-analysis of the 2 cohorts (best p = 4.8 x 10(-7) for the SKAT, MAC >= 1).ConclusionGene-based tests indicated an association for FBLN2, a gene encoding an extracellular matrix protein implicated in vascular wall remodeling, but independent validation in larger cohorts is warranted. We did not identify any significant associations for single low-frequency genetic variants.