A highly informative CA/GT repeat polymorphism in intron 38 of the human neurofibromatosis type 1 (NF1) gene

We describe a polymorphic microsatellite in intron 38 of the neurofibromatosis type 1 (NF1) gene. The microsatellite consists of a CA/GT dinucleotide repeat detecting 8 alleles; it has a heterozygosity of 82 %.     

Mapping the short arm of human chromosome 16

Physical mapping of 13 different breakpoints on the short arm of chromosome 16 using previously mapped probes and the subsequent mapping of additional probes enabled the division of this portion of the chromosome into six different intervals. D16S94 was mapped between HBA and D16S80 and is closer to PKD1 than either HBA or D16S80. A tight linkage group which includes FRA16A, D16S8, and D16S79 was identified. Seven breakpoints, including FRA16A, could not be separated by probe localizations. This study provides the basis for the development of detailed maps of the short arm of chromosome 16.     

A highly polymorphic dinucleotide repeat on the proximal short arm of the human X chromosome: linkage mapping of the synapsin I/A-raf-1 genes.

A compound (AC)n repeat located 1,000 bp downstream from the human synapsin I gene and within the last intron of the A-raf-1 gene has been identified. DNA data-base comparisons of the sequences surrounding the repeat indicate that the synapsin I gene and the A-raf-1 gene lie immediately adjacent to each other, in opposite orientation. PCR amplification of this synapsin I/A-raf-1 associated repeat by using total genomic DNA from members of the 40 reference pedigree families of the Centre d'Etude du Polymorphisme Humaine showed it to be highly polymorphic, with a PIC value of .84 and a minimum of eight alleles. Because the synapsin I gene has been mapped previously to the short arm of the human X chromosome at Xp11.2, linkage analysis was performed with markers on the proximal short arm of the X chromosome. The most likely gene order is DXS7SYN/ARAF1TIMPDXS255DXS146, with a relative probability of 5 x 10(8) as compared with the next most likely order. This highly informative repeat should serve as a valuable marker for disease loci mapped to the Xp11 region.     

The gene for human carbonic anhydrase VI(CA6) is on the tip of the short arm of chromosome 1

The gene encoding the human secreted carbonic anhydrase isozyme CAVI(CA6) maps to chromosome 1 by Southern analysis of a somatic cell hybrid panel and to 1p36.22----p36.33 by in situ hybridization. CA6 is therefore not linked to the cytoplasmic carbonic anhydrase genes on chromosome 8 or to CA7 on chromosome 16.     

A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p.

A compound imperfect dinucleotide repeat element, [CA]4TTTGT[CT]7[CA]9AA[CA]4CCACATA[CA]3, was found approximately 10 kb 3' to the human glucokinase gene (GCK) from analysis of contiguous genomic DNA obtained from a bacteriophage lambda chromosome walk. Direct human genomic sequencing revealed the source of polymorphism to be variable numbers of CT and CA repeats. Altogether six alleles that range in length from +10 to -15 nucleotides compared to the most common (Z) allele have been identified. Alleles Z, Z + 2, and Z + 4 were present in American Blacks, Pima Indians, and Caucasians, with somewhat varied frequencies among the groups. Two alleles, Z + 10 and Z - 15, appear to be unique to American Blacks, while a Z + 6 allele was observed only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the CEPH reference pedigree collection is 44% and the PIC 0.44. The polymorphism is assayed by PCR amplification and resolution of 32P-end-labeled products (ranging in length from 180 to 205 bp) on denaturing polyacrylamide sequencing gels. Using the PCR assay, the human glucokinase gene was physically localized to chromosome 7 in a panel of rodent/human somatic cell lines. Genetic analysis in CEPH pedigrees placed the dinucleotide repeat element, and thereby the human glucokinase gene, on chromosome 7p between TCRG and a RFLP locus D7S57. The glucokinase dinucleotide repeat genetic marker can now be used to assess the role of the glucokinase gene in diabetes by population association studies. In addition, this repeat marker and others flanking it on chromosome 7 can be used in linkage studies with families segregating the disorder.     

Fine mapping of a pistilloid-stamen (PS) gene on the short arm of chromosome 1 in rice.

A novel floral organ mutant of rice (Oryza sativa L. subsp. indica), termed pistilloid-stamen (ps) here, has flowers with degenerated lemma and palea, with some stamens transformed into pistils and pistil-stamen chimeras. Genetic analysis confirmed that the ps trait is controlled by a single recessive gene. F2 and F3 segregation populations derived from PS ps heterozygote crossed with Oryza sativa subsp. indica 'Luhui-17' (PS PS) were used for molecular mapping of the gene using simple sequence repeat (SSR) markers. With 97 recessive individuals from an F2 segregation population, the ps locus was preliminarily mapped 6.2 cM distal to marker RM6324 and 3.1 cM proximal to marker RM6340 in the terminal region of the short arm of chromosome 1. With a large F3 segregation population, the gene was fine-mapped between markers RM6470 and RM1141, at distances of 0.10 and 0.03 cM to each marker, respectively. The position of the ps gene was finally located within a 20 kb physical region containing 3 annotated putative genes. One of them, encoding a protein with a single C2H2 zinc-finger domain, may be the candidate gene for PS.     

A (CA)n repeat polymorphism for the human skeletal muscle alpha-actinin gene ACTN2 and its localization on the linkage map of chromosome 1.

A CA dinucleotide repeat polymorphism has been identified for the skeletal muscle alpha-actinin gene ACTN2. The observed heterozygosity is 44% (predicted heterozygosity 50%, PIC 0.47). This polymorphic marker has been localized between D1S74 and D1S103 on the multipoint linkage map of chromosome 1 at a position 44.4 cM from the most distal marker D1S68 at 1 qter.     

The human neurofilament gene (NEFL) is located on the short arm of chromosome 8

We have localized the gene coding for the human neurofilament light chain (NEFL) to chromosome band 8p2.1 by Southern blotting of DNA from hybrid cell panels and in situ hybridization to metaphase chromosomes.     

Mapping the human liver/islet glucose transporter (GLUT2) gene within a genetic linkage map of chromosome 3q using a (CA)n dinucleotide repeat polymorphism and characterization of the polymorphism in three racial groups.

The human liver/islet glucose transporter (GLUT2), a candidate gene for diabetes, has been incorporated into a genetic linkage map for chromosome 3q using a (CA)n dinucleotide repeat polymorphism adjacent to the 3'-end of exon 4a. We have found a total of nine alleles ranging in length from 153 to 169 nucleotides in three racial groups and have determined the precise structure of the variable region for four of the alleles by DNA sequencing. Five alleles were found to be common to the American Black, Caucasian, and Pima Indian racial groups studied. One allele (169 bp) was unique to American Blacks, and another rare allele (153 bp) was found only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the Caucasian (CEPH) reference pedigree collection is 60%, for American Blacks 71%, and for Pima Indians 53%. An independent study recently identified the same dinucleotide repeat and found six alleles in a Caucasian population (Froguel et al., 1991), a result that we confirm; however, our sequencing data indicate a different molecular structure for the polymorphism for some of the alleles. We have constructed a new genetic linkage map of chromosome 3q uniquely placing the GLUT2 gene between flanking markers D3S26 and D3S43. The genetic map consists of 23 loci (25 RFLPs and 2 (CA)n dinucleotide repeat markers) with 14 markers uniquely localized with odds of at least 1000:1. Three genes (FTHL4, TF, GLUT2) are integrated into the map, which spans a sex-average distance of 147.3 cM, 103.8 cM in males and 227.0 cM in females.(ABSTRACT TRUNCATED AT 250 WORDS)     

A radiation hybrid map of the proximal short arm of the human X chromosome spanning incontinentia pigmenti 1 (IP1) translocation breakpoints.

Radiation hybrid mapping was used in combination with physical mapping techniques to order and estimate distances between 14 loci in the proximal region of the short arm of the human X chromosome. A panel of radiation hybrids containing human X-chromosomal fragments was generated from a Chinese hamster-human cell hybrid containing an X chromosome as its only human DNA. Sixty-seven radiation hybrids were screened by Southern hybridization with sets of probes that mapped to the region Xp11.4-Xcen to generate a radiation hybrid map of the area. A physical map of 14 loci was constructed based on the segregation of the loci in the hybrid clones. Using pulsed-field gel electrophoresis (PFGE) analyses and a somatic cell hybrid mapping panel containing naturally occurring X; autosome translocations, the order of the 14 loci was verified and the loci nearest to the X-chromosomal translocation breakpoints associated with the disease incontinentia pigmenti 1 (IP1) were identified. The radiation hybrid panel will be useful as a mapping resource for determining the location, order, and distances between other genes and polymorphic loci in this region as well as for generating additional region-specific DNA markers.     

The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4.

Atrial natriuretic factors (ANF) are polypeptides having natriuretic, diuretic, and smooth muscle-relaxing activities that are synthesized from a single larger precursor: pronatriodilatin. Chromosomal assignment of the gene coding for human pronatriodilatin was accomplished by in situ hybridization of a [3H]-labeled pronatriodilatin probe to human chromosome preparations and by Southern blot analysis of somatic cell hybrid DNAs with normal and rearranged chromosomes 1. The human pronatriodilatin gene was mapped to the distal short arm of chromosome 1, in band 1p36. Southern blot analysis of mouse X Chinese hamster somatic cell hybrids was used to assign the mouse pronatriodilatin gene to chromosome 4. This assignment adds another locus to the conserved syntenic group of homologous genes located on the distal half of the short arm of human chromosome 1 and on mouse chromosome 4.     

The human apolipoprotein B-100 gene: a highly polymorphic gene that maps to the short arm of chromosome 2

Using a cloned cDNA of apolipoprotein B-100 as hydridization probe, we have found high frequence polymorphisms in the apoB-100 gene involving sites for the restriction enzymes EcoRI, BamHI, and HindIII. The major EcoRI polymorphisms involved a 17 kb vs 15 kb variant. The incidence of the various phenotypes was estimated. In addition, other complex polymorphisms involving MspI and TaqI sites were also noted. [32P]-labeled apoB-100 cDNA was used as a probe in chromosome mapping studies to detect the human apoB-100 structural gene sequence in human-Chinese hamster and human-mouse cell hybrids. Southern blot analysis of 14 hybrids localized the gene to the short arm of human chromosome 2.     

Linkage mapping of D21S171 to the distal long arm of human chromosome 21 using a polymorphic (AC)n dinucleotide repeat

Summary An (AC)_n repeat within the anonymous DNA sequence D21S171 was shown to be highly polymorphic in members of the 40 Centre d'Etude du Polymorphisme Humain (CEPH) families. Ten different alleles at this marker locus were detected by electrophoresis on polyacrylamide gels of DNA amplified by the polymerase chain reaction (PCR) using primers flanking the (AC)_n repeat. The observed heterozygosity was 66%. PCR amplification of DNA from somatic cell hybrids mapped D21S171 to human chromosome 21, and linkage analysis localized this marker close to the loci CD18, PFKL, D21S113 and D21S112 in chromosomal band 21q22.3. In CEPH family 12 a de novo allele has been observed in a maternally derived chromosome.     

The gene encoding human vimentin is located on the short arm of chromosome 10.

The gene for vimentin, an intermediate-filament protein, is growth regulated. We used Southern blot analysis and in situ chromosome hybridization to determine the location of the human vimentin gene. Our results show that there is only one copy of the vimentin gene and that it is located on the short arm of chromosome 10 (10pter-10q23) close to the interleukin-2 receptor gene, which is also growth regulated. In situ hybridization studies suggest that the most likely location of the vimentin gene is 10p13. Sequence similarities and homologies of human vimentin to other genes are presented.     

The human C-reactive protein gene (CRP) and serum amyloid P component gene (APCS) are located on the proximal long arm of chromosome 1

The genes encoding two pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP), are located on the proximal long arm of human chromosome 1. Mapping of the CRP and SAP genes between the centromere and band q32 was achieved by Southern blot analysis of DNA from a panel of human × Chinese hamster somatic cell hybrids carrying defined fragments of human chromosome 1. Both genes were localized more precisely between bands q12 and q23 by in situ hybridization to human metaphase chromosomes.     

Mapping allelic deletions on the short arm of human chromosome 3 in kidney neoplasms]

Allelic deletions along the short arm of human chromosome 3 were mapped in 57 pairs of DNA samples from tumor and normal tissue of renal carcinoma patients in order to locate potential tumor suppressor genes. Twenty highly polymorphic microsatellite markers were used for deletion mapping. Allelic deletions were found in most of the samples (91%). Extended terminal deletions (56%) prevailed over shorter internal and multiple deletions and dominated (65%) in the most aggressive histopathological kidney cancer subtype, clear-cell carcinoma. Frequency analysis of loss of heterozygosity allowed detection of the human chromosome 3 regions most essential for renal carcinomas: the region adjacent to the gene VHL (3p26-p25), the region of homozygous deletions AP20 (3p22-p21.33), and a new region between markers D3S2420 and D3S2409 (3p21.31, 2.2 Mbp).     

Linkage mapping of the highly informative DNA marker D21S156 to human chromosome 21 using a polymorphic GT dinucleotide repeat

A (GT)n repeat within the anonymous DNA sequence D21S156 was shown to be highly polymorphic in DNA from members of the 40 CEPH families. At least 12 alleles of this locus were recognized by electrophoresis on polyacrylamide gels of DNA amplified by the polymerase chain reaction (PCR) using primers flanking the (GT)n repeat. The polymorphism information content was 0.82. PCR amplification of DNA from somatic cell hybrid lines mapped D21S156 to human chromosome 21 and linkage analysis localized this marker close to the loci ETS2, D21S3, and HMG14 on chromosomal band 21q22.3. This polymorphism is highly informative and can serve as an anchor locus for human chromosome 21.     

Clustering of the human CLCA gene family on the short arm of chromosome 1 (1p22-31).

The CLCA gene family is a novel family of calcium-activated chloride channels. Several family members have recently been cloned from different mammalian species with distinct, highly tissue-specific expression patterns. Here, we describe radiation hybrid mapping of the human CLCA2 and CLCA3 genes using the Genebridge 4 panel. Both genes were mapped to adjacent loci on the short arm of chromosome 1 (1p22-31), a region to which the human CLCA1 had been assigned earlier. The results show clustering of all human CLCA family members known so far despite their moderately low levels of sequence homology and their heterogeneous expression patterns.