The three genes of the human FCGR1 gene family encoding Fc gamma RI flank the centromere of chromosome 1 at 1p12 and 1q21
CYTOGENETICS AND CELL GENETICS
Authors: Maresco, DL; Chang, E; Theil, KS; Francke, U; Anderson, CL
Abstract
The high-affinity receptor for immunoglobulin G, Fc gamma RI (FCGR1), is encoded by a family of three genes within humans that share over 98% of DNA sequence homology. Efforts to define the location of the FCGR1 genes within chromosome 1 have been made to determine if they are tightly linked to the five other FCGR genes present at 1q23. Our results, obtained through both fluorescence in situ hybridization analysis of human cells and Southern analysis of cell lines containing Ip and Iq, show instead that the three genes flank the centromere of chromosome 1 at bands 1p12 and 1q21. FCGR1B was found at 1p12, whereas both FCGR1A and FCGR1C were localized to 1q21. This places the FCGR1 gene family within a large pericentric linkage group which is conserved between humans and mice. We hypothesize that the three FCGR1 genes were separated by a pericentric inversion, known to have occurred on human chromosome 1, which relocated FCGR1A and FCGR1C to the long arm and left FCGR1B positioned on the short arm. We have also performed FCGR1 gene copy number experiments which indicate the existence of three FCGR1 genes within the human genome.
Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
SCIENTIFIC REPORTS
Authors: Jenum, Synne; Dhanasekaran, S.; Lodha, Rakesh; Mukherjee, Aparna; Saini, Deepak Kumar; Singh, Sarman; Singh, Varinder; Medigeshi, Guruprasad; Haks, Marielle C.; Ottenhoff, Tom H. M.; Doherty, Timothy Mark; Kabra, Sushil K.; Ritz, Christian; Grewal, Harleen M. S.
Abstract
The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress "Towards Zero Deaths". Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70-80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intrathoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups "upstream" towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or "downstream" towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).