A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31.

Interstitial deletion or loss of chromosome 5, del(5q) or -5, is a frequent finding in myeloid leukemias and myelodysplasias, suggesting the presence of a tumor suppressor gene within the deleted region. In our search for this gene, we identified a candidate, 5qNCA (LOC51780), which lies within a consistently-deleted segment of 5q31. 5qNCA expresses a 7.2-kb transcript with a 5286-bp open reading frame which is present at high levels in heart, skeletal muscle, kidney, placenta, and liver as well as CD34+ cells and AML cell lines. 5qNCA encodes a 191-kD nuclear protein which contains a highly-conserved C-terminus containing a zinc finger with the unique spacing Cys-X2-Cys-X7-His-X2-Cys-X2-Cys-X4-Cys-X2-Cys and a jmjC domain, which is often found in proteins that regulate chromatin remodeling. Expression of 5qNCA in a del(5q) cell line results in suppression of clonogenic growth. Preliminary sequence results in AML and MDS samples and cell lines has revealed a possible mutation in the KG-1 cell line resulting in a THR to ALA substitution that has not been found in over 100 normal alleles to date. We propose 5qNCA is a good candidate for the del(5q) tumor suppressor gene based on its predicted function and growth suppressive activities, and suggest that further mutational and functional study of this interesting gene is warranted.

[Specificity of lipid and lipoprotein status in healthy students at the University of Novi Sad]. / Specificnosti lipidskog i lipoproteinskog statusa zdravih studenata Novosadskog Univerziteta.

INTRODUCTION: The aim of this study was to determine the frequency of hyperlipoproteinemias and normolipidemic dyslipoproteinemias, and distribution of desirable, borderline and high-risk values of certain lipid status parameters in healthy young individuals. MATERIAL AND METHODS: In this investigation we examined 213 students of the University of Novi Sad of both genders, 20-30 years of age. Standard biochemical methods were used to determine values of total serum cholesterol, triglycerides, HDL cholesterol, and lipoproteins by cellulose acetate electrophoresis. The level of LDL cholesterol and LDL/HDL cholesterol and total/HDL cholesterol ratios were calculated. RESULTS: In this group hyperlipoproteinemia was established in 42.3% of cases and normolipidemic dyslipoproteinemia in 65.3%. Total serum cholesterol was minimally elevated in 39.0% of tested students, elevated with high risk in 3.3% and triglycerides were minimally elevated in 1.0%. Presence of elevated LDL cholesterol (24.4% minimally and 13.2% with high risk) is remarkably significant. HDL cholesterol is minimally decreased in 54.0% of tested students, and severely in 3.3%. DISCUSSION: The tested parameters deviate from desirable levels with an alarmingly high frequency, given the fact that this is a group of healthy young individuals with no previous history of lipid and lipoprotein metabolism disorders. It can be hypothesized that a joint hyper Lp(a)-lipoproteinemia can exist with a significant occurrence. These results could be associated with similar disorders in families of tested students, unhealthy food habits and lifestyle, use of oral contraceptives and smoking. CONCLUSION: Our results point to the need for performing gradual laboratory diagnostic procedures for routine check-ups in students.

Delineation of a minimal interval and identification of 9 candidates for a tumor suppressor gene in malignant myeloid disorders on 5q31.

Interstitial deletion or loss of chromosome 5 is frequent in malignant myeloid disorders, including myelodysplasia (MDS) and acute myeloid leukemia (AML), suggesting the presence of a tumor suppressor gene. Loss of heterozygosity (LOH) analysis was used to define a minimal deletion interval for this gene. Polymorphic markers on 5q31 were identified using a high-resolution physical and radiation hybrid breakpoint map and applied to a patient with AML with a subcytogenetic deletion of 5q. By comparing the DNA from leukemic cells to buccal mucosa cells, LOH was detected with markers D5S476 and D5S1372 with retention of flanking markers D5S500 to D5S594. The D5S500-D5S594 interval, which covers approximately 700 kb, thus represents a minimal localization for the tumor suppressor gene. Further refinement of the physical map enabled the specification of 9 transcription units within the encompassing radiation hybrid bins and 7 in flanking bins. The 9 candidates include genes CDC25, HSPA9, EGR1, CTNNA1, and 5 unknown ESTs. Reverse-transcription polymerase chain reaction confirms that all of them are expressed in normal human bone marrow CD34(+) cells and in AML cell lines and thus represent likely candidates for the MDS-AML tumor suppressor gene at 5q31.

A radiation hybrid breakpoint map of the acute myeloid leukemia (AML) and limb-girdle muscular dystrophy 1A (LGMD1A) regions of chromosome 5q31 localizing 122 expressed sequences.

We have constructed a high-resolution map of a 6-Mb interval of human chromosome 5, band q31, incorporating 175 sequence tagged sites, of which 33 are genetic polymorphisms and 122 are nonredundant expressed sequences. The map was assembled initially as a YAC contig, incorporating data from radiation hybrid maps. To improve resolution and to identify errors in the databases, a radiation hybrid breakpoint map was developed for the interval, which included hybrids from both Stanford G3 and GeneBridge 4 panels. This novel approach facilitated the integration of one RH panel with another and enabled the identification and localization of new, previously unmapped ESTs from the radiation hybrid databases. ESTs were assembled into overlapping transcription units and ordered with respect to polymorphic markers in the region, resulting in a comprehensive map that incorporates markers from multiple different types of maps. This map of 5q31 will facilitate gene discovery efforts for several disorders, including limb-girdle muscular dystrophy type 1A and the genes deleted in acute myeloid leukemias and myelodysplasia. The study demonstrates the utility of a radiation hybrid breakpoint panel for correction of map errors and for the efficient identification of new transcript units in a large genomic interval.