Feline arylsulfatase B (ARSB): isolation and expression of the cDNA, comparison with human ARSB, and gene localization to feline chromosome A1.

Arylsulfatase B (ARSB) is the lysosomal enzyme that catalyzes the hydrolysis of 4-sulfate groups from N-acetylgalactosamine 4-sulfate moieties on the glycosaminoglycans, dermatan sulfate and chondroitin sulfate A. In man, a deficiency of this enzymatic activity causes the lysosomal storage disorder, Maroteaux-Lamy disease (mucopolysaccharidosis Type VI; MPS VI). MPS VI in Siamese cats also has been described, and the comparative pathologic and biochemical abnormalities of the human and feline disorders have been well characterized. The present study describes the isolation and expression of cDNAs encoding feline ARSB and the assignment of the feline ARSB gene to feline chromosome A1. The full-length feline ARSB cDNA sequence is 1939 bp, including 3 and 328 bp of 5' and 3' untranslated sequences, respectively, and a 1608-bp open reading frame encoding 535 amino acids. The predicted human and feline ARSB proteins are 91% identical and 94% similar. However, despite this high homology, the predicted feline ARSB polypeptide has nine cysteine residues, while the human enzyme has eight. The presence of the extra cysteine residue at position 451 in the feline enzyme may explain why feline ARSB is a homodimer and the human enzyme is a monomer. To facilitate comparative structure/function studies of the human and feline enzymes and to initiate somatic gene therapy trials in the MPS VI cats, a full-length feline ARSB cDNA was reconstructed from a 1440-bp partial cDNA and an ARSB fragment amplified from feline first-strand cDNA by the polymerase chain reaction. The functional integrity of this cDNA was demonstrated by transient expression in human embryonic kidney cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double autosomal trisomy (1q21.2----qter and 14pter----q13) in a female fetus with nuchal oedema

In this report we describe the prenatal diagnosis of a double autosomal trisomy (1q21.2----qter and 14pter----q13) in a female fetus with nuchal oedema, microphthalmia of the left eye and craniofacial dysmorphism. Cytogenetic examination of the parents revealed an autosomal reciprocal 1q/14q translocation with karyotype: 46,XX,t(1;14)(q21.2;q13) in the mother.     

Assignment of the gene for human arylsulfatase B, ARSB, to chromosome region 5p11----5qter

The structural gene coding for human arylsulfatase B, ARSB, is assigned to 5p11----5qter by analysis of somatic cell hybrids isolated from two separate fusions of human fibroblasts carrying a translocation involving chromosome 5 with the Chinese hamster cell line a3.     

Regional localization of the human transferrin receptor gene to 3q26.2----qter.

Transport of iron across the cell membrane is mediated by the iron-binding serum protein, transferrin, and its cell-surface receptor. Transferrin receptor is required for cell proliferation and may play a functional role in the pathogenesis of iron-storage disorders and some neoplasias. To better understand the possible involvement of transferrin receptor in such disorders, we have determined the chromosomal locus of the receptor gene by in situ hybridization. The human transferrin receptor gene was thus mapped to 3q26.2----qter, a region of chromosome 3 that appears to be involved in metal transport and that is subject to nonrandom structural rearrangements associated with neoplasia.     

Regional localization of the human platelet-derived endothelial cell growth factor (ECGF1) gene to chromosome 22q13.

Using in situ hybridization and a panel of human X rodent somatic cell hybrids, which discriminates between four different regions of human chromosome 22, we have localized the gene for human platelet-derived endothelial cell growth factor (ECGF1) to 22q13, placing ECGF1 distal to the PDGFB locus at 22q12.3----q13.1.     

Partial trisomies 13 and 22 due to nondisjunction of a maternal reciprocal translocation,t(13;22)(q22;q11)

Summary A family is reported in which the propositus has an extra G-like chromosome with an unusual G-banding pattern. Cytogenetic family studies showed that the mother is a carrier of a balanced reciprocal translocation t(13;22), which does not affect the size and morphology of the chromosomes involved. The propositus has a 47,XY,+der(22),t(13;22)(q22;q11) karyotype and is therefore partially trisomic for the distal third of the long arm of chromosome 13 and for a very small part of chromosome 22. The clinical findings are presented and compared with those of other reported cases of partial trisomies 13 and 22.     

Translocation t(11;14) and trisomy 11q13----qter in multiple myeloma

A 14q+ marker with extra material derived from chromosome 11 long arm, i.e. segment q13----qter, has been found in cells from a pleural effusion in a patient with highly malignant multiple myeloma. The segment 11q13----qter was trisomic because of the presence of both apparently normal homologous chromosomes 11.     

Duplication 16q12----qter arising from 3:1 segregation in a 46,XX,t(13;16) (q12;q12) mother

A congenitally abnormal female baby was found to have the karyotype 46, XX, +der (16) t (13; 16) (q12;q12) mat. GTG, QFQ, CBG, THA and Ag-NOR banding techniques allowed the identification of the abnormal chromosomes in the proposita and in the translocation carriers through three generations. Duplication 16q resulted from 3:1 segregation in the carrier mother. The hypothesis of a specific meiotic segregation for this translocation is discussed. The phenotypic effects of proximal 16q duplications are analysed together with other four reported cases, which have similar duplicated segment and no other relevant chromosomal abnormality.     

A new locus for hereditary gingival fibromatosis (GINGF2) maps to 5q13-q22

Gingival fibromatosis (GINGF) is an oral disorder characterized by enlargement of the gingiva. It occurs either as the sole phenotype or combined with other symptoms. Thus far, one GINGF locus has been mapped on chromosome 2, at 2p21, and a second possible locus has been mapped to 2p13. However, the genes responsible for this disorder have not been elucidated. We identified a four-generation Chinese GINGF family in which the disease manifests within 1 year after birth. After exclusion of the two known GINGF loci in this family, we performed a genome-wide search to map the chromosome location of the responsible gene. We identified a new locus, GINGF2, on chromosome 5q13-q22 with a maximum two-point lod score of 4.31 at D5S1721 (theta = 0.00). Haplotype analysis placed the critical region in the interval defined by D5S1491 and D5S1453. Within this region, calcium/calmodulin-dependent protein kinase IV (CAMK4) is a strong candidate.     

Chromosomal localization to 3q21----qter and two TaqI RFLPs of the human prostate-specific acid phosphatase gene (ACPP)

The chromosomal location of the gene encoding human prostate-specific acid phosphatase (ACPP) was determined by Southern blotting analysis of panels of human x rodent (mouse or Chinese hamster) somatic cell hybrids, using the PAP-1007 and PAP-1004EP ACPP cDNA probes. The ACPP gene was assigned to chromosome 3, which was confirmed by screening a chromosome 3-specific genomic library. Sublocalization of this gene was carried out using hybrids that had retained only various portions of human chromosome 3. The ACPP gene was found to segregate specifically with the chromosomal segment 3q21----qter. Analysis of Southern blots of TaqI-digested DNAs from unrelated individuals and members of large families from northern Finland revealed two simultaneous diallelic restriction fragment length polymorphisms (RFLPs), A and B, when using either PAP-1004EP or PAP-1006A ACPP cDNA probes, but not the 5' flanking PAP-1007 probe. Allele frequencies for polymorphism A were .09 (A1) and .91 (A2), and for polymorphism B, .38 (B1) and .62 (B2). There appears to be only a very minor linkage disequilibrium (chi 2 = 1.12, 0.35 greater than P greater than 0.25) between the two TaqI RFLPs at the ACPP locus. For reasons presently unknown, homozygotes for polymorphism B appear to be overrepresented. These polymorphisms could be of importance in characterizing human prostate cancer.     

Localization of the human myelin basic protein gene (MBP) to region 18q22----qter by in situ hybridization

A restriction endonuclease fragment derived from a cloned portion of human genomic DNA corresponding to the myelin basic protein gene has been used to map the position of this gene by in situ hybridization to human metaphase chromosomes. Ten percent of the radioactively labeled sites observed were on chromosome 18. Eighty-four percent of the grains on chromosome 18 were located within the region corresponding to 18q22----qter. This represents a greater than 10-fold increase in labeling at this position over the background grain distribution found along all of the other chromosomes.     

Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter.

The structural gene for human kininogen (KNG) was localized to chromosome 3q26----qter by in situ hybridization. The assignment substantiates the evolutionary relationship of kininogen to two other members of the cystatin superfamily, alpha-2-HS-glycoprotein and histidine-rich glycoprotein, which also map to chromosome 3.     

Assignment of the human intestinal Na+/glucose cotransporter gene (SGLT1) to the q11.2----qter region of chromosome 22

The chromosomal location of the human intestinal Na+/glucose cotransporter gene (SGLT1) was determined using human cDNA and genomic probes for this transporter gene. Southern blot analysis of genomic DNA from 15 mouse-human somatic cell hybrids showed that the human gene for this transporter resides on chromosome 22. Analysis of hamster-human hybrids selectively retaining chromosome 22 or a portion of it allowed specific assignment of the locus to the q11.2----qter region of chromosome 22. A restriction fragment length polymorphism was identified with EcoRI.     

Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p?=?1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p?=?7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.