Jordi Guimerà

Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressed in the primitive ventricle of the heart and during neurogenesis

We have demonstrated that DSCR1 acts as a negative regulator of calcineurin-mediated signaling and that its transcript is overexpressed in the Down syndrome (DS) fetal brain. To evaluate the possible involvement of DSCR1 in DS, we have cloned the mouse gene and analyzed its expression pattern in the central nervous system (CNS). Early expression of Dscr1 is detected mainly in the heart tube and in the CNS in rhombomere 4 and the pretectum. From embryonic day 14.5 onwards, Dscr1 is widely distributed in the CNS but becomes more restricted as the brain matures. We confirmed its neuronal expression pattern in the adult, preferentially in Purkinje and pyramidal cells, by double labeling with glial fibrillary acidic protein. We also show that although Dscr1 is present in trisomy in the Ts65Dn mouse, the adult brain expression pattern is not significantly altered. This expression pattern indicated that Dscr1 is a developmentally regulated gene involved in neurogenesis and cardiogenesis and suggests that it may contribute to the alterations observed in these organ systems in DS patients.

Integration of 30 CA-repeat markers into the cytogenetic, genetic and YAC maps of human chromosome 21.

The number of polymorphic DNA markers developed for the whole human genome during the last 2 years has been vastly increased. For this reason, the genetic map is continuously improving, but the cytogenetic and physical maps are not progressing at the same speed. Therefore, there is a need to integrate genetic, cytogenetic and physical mapping data. We have developed and localized on the breakpoint map of human chromosome 21 thirty microsatellite markers. Twenty of them have been used in the construction of a genetic map of chromosome 21, which contains a total of 44 markers. This map has 39 uniquely placed loci at 23 anchor points, ordered with odds of at least 1,000:1. The sex average length of the map is 64.4 cM, with the male and female lengths being 49.4 and 79.2 cM, respectively. Twenty-six of these newly developed markers have been localised on the CEPH/Généthon and Joint YAC Screening Effort YACs. Although these microsatellites were found uniformly spread along chromosome 21, the detection of various markers in the same or adjacent YACs suggests that CA-repeat microsatellites are clustered in several regions. The localization of these markers on the cytogenetic, genetic and YAC maps has provided a refined location for them and is a step further towards the construction of an integrated map of HC21.

Minibrain (MNBH) is a single copy gene mapping to human chromosome 21q22.2

We have identified a human homologue of the Drosophila mnb gene (MNBH) on chromosome 21, while another study mapped an EST clone (R38268) with similarity to minibrain to human chromosome 1. This report describes the mapping of MNBH to a single locus on human chromosome 21q22.2 by FISH and Southern blotting. Comparison of the similarities between the two sequences and mnb demonstrates that MNBH on chromosome 21 is the true human homologue of Drosophila mnb.

Five new microsatellite polymorphisms at the q21 region of human chromosome 21

Five clones, containing polymorphic CA-repeat sequences, have been isolated from a specific human chromosome 21 phage library and have been localised to band q21 of chromosome 21 using a somatic cell hybrid panel. These highly repetitive sequences (D21S1263, D21S1264, D21S1415, D21S1417 and D21S1420) have been characterised in the CEPH reference parents and have heterozygosities ranging from 0.30 to 0.81 and an average polymorphism information content (PIC) of 0.62. The relative order of these markers, based on the somatic cell hybrid panel, is cen-D21S1417, D21S1420-D21S1263, D21S1415-D21S1264-tel. The most polymorphic marker (D21S1264) has been included in the chromosome 21 genetic map. They have also been localised in the CEPH/ Généthon YAC panel, providing a refined localisation of these polymorphic sequences. These five CA-repeat markers should provide a better characterisation of the q21 region of chromosome 21.