SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The human aldose reductase (AR) gene has been mapped to chromosome 7 using the polymerase chain reaction to specifically amplify the human AR sequence in hamster/human hybrid DNA and also in mouse/human monochromosome hybrids. The assignment to chromosome 7 was confirmed by in situ hybridisation to human metaphase chromosomes using a novel, rapid hybridisation, method giving a regional localisation at 7q35.
As evidenced by a large pedigree with 21 affected members, acrokeratoelastoidosis (AKE) is an autosomal dominant skin disease (10185; McKusick 1978). Linkage with genetic markers already assigned to human chromosomes could help to map the gene for this disease. Therefore 22 markers were investigated in 61 members of the AKE family. Loose linkage is possible between AKE and ACP1, IGKC, and Jk, but the estimated recombination fractions do not reach significant deviations from 0.5. However, since the three marker loci have been previously assigned to chromosome 2, the AKE locus might be assigned tentatively to the same chromosome. Of the provisionally and inconsistently assigned markers, only blood group P is seen to be in linkage with HLA.
In order to expand the comparative map between human chromosome 3 (HSA3) and porcine chromosome 13 (SSC13), seven genes from HSA3 were mapped on SSC13 by fluorescence in situ hybridisation (FISH), viz. ACAA1, ACPP, B4GALT4, LTF, MYLK, PDHB and RARB. With a view to integrating this expanded comparative map with the existing SSC13 linkage map, we used the INRA-University of Minnesota porcine Radiation Hybrid panel (IMpRH) to localize more precisely and to order 15 genes on the SSC13 map, viz. ACPP, ADCY5, APOD, BCHE, CD86, DRD3, GAP43, PCCB, RAF1, RHO, SI, TF, TFRC, TOP2B and ZNF148. In this way, we were able to create an integrated map, containing 38 type I and 81 type II markers, by correlating the linkage, radiation hybrid (RH) and cytogenetic maps of SSC13. This integrated map will give us the opportunity to take maximal advantage of the comparative mapping strategy for positional candidate cloning of genes responsible for economically important traits.
The human NK-2 receptor gene has been mapped to chromosome 10 using the polymerase chain reaction to amplify specifically the human NK-2 receptor sequence in hamster/human hybrid DNA and also in mouse/human monochromosome hybrids. The assignment to chromosome 10 was confirmed by in situ hybridisation to human metaphase chromosomes, giving a regional localisation of 10q11-21.
The region 9E1-2 - 10B1-2 of the Drosophila melanogaster X chromosome was analysed under the light (LM) and the electron (EM) microscope using different fixatives and an EM map of the region was constructed. EM analysis revealed 21 bands in the region 9E1-2 - 10B1-2 instead of 36 bands in Bridges' map. This discrepancy mainly results from the fact that 14 bands indicated as "doublets" by Bridges appear as a single bands. No doublets were found in the whole 9B1-2 - 10C1-2 region after fixation of salivary glands in 3% glutaraldehyde, 3% formaldehyde and 3 : 1 ethanol-acetic acid mixture. 45% acetic acid is the only fixative which results in strongly vacuolated appearance of the bands. - The break points of 30 chromosome rearrangements in the region 9E1-2 - 10B1-2 were located under EM or LM within the limits of the EM map of this region.
We have developed a genetic linkage map of 19 markers (including nine genes) on human chromosome 17, providing 13 reference points along virtually the entire length of this chromosome. The map covers an estimated 149 cM in length (sex-averaged), with a total length of 214 cM in females and 95 cM in males. This sex difference appears to be significant along virtually the entire length of the map. This map will be useful both for providing reference points for fine structure genetic and physical mapping and for genetic linkage studies of diseases, including von Recklinghausen neurofibromatosis and Charcot-Marie-Tooth disease.
To identify genes that map on human chromosome 21 (HC21) and that may contribute to the phenotype of Down syndrome (DS), exon trapping was applied to cosmid DNA from an HC21-specific library LL21NCO2-Q. More than 550 potential exons were cloned and partially characterized. One of these, hmc23b04 (GenBank X88270) showed strong homology to the Drosophila Enhancer of zeste protein (GenBank U00180) from amino acid 665 to 694 (p = 7.6 x 10(-11). We have cloned the full-length cDNA for this human homolog of the Drosophila E(z) gene (termed EZH2) and mapped it to within YACs 64f11 and 809b11 between markers D21S65 and ERG on human chromosome 21q22.2. Sequence analysis indicates that EZH2 encodes a 746-amino-acid polypeptide that shows 60.5% identity to the Drosophila E(z) protein and contains a trithorax-like domain and a DNA-binding motif. Northern blot analysis revealed that EZH2 is expressed in several tissues. Alternatively spliced mRNA species have been observed. The Drosophila E(z) protein is a member of the polycomb group genes that maintain homeotic gene repression and are thought to control gene expression by regulating chromatin. The strong sequence conservation suggests a possible function of EZH2 in regulation of gene transcription and chromatin structure; it may therefore contribute to certain phenotypes of Down syndrome by altered regulation of its target genes.
Chromosomal localization has been established for many genetic traits. Gene mapping may lead to the identification of disease genes, an understanding of pathogenesis, and the development of rational therapy, as well as facilitating antenatal diagnosis and genetic counselling. 'The new genetics' is therefore of great interest to the clinician. Unfortunately the complex technology and unfamiliar vocabulary of molecular biology often deter non-specialists from keeping abreast of these developments. This account explains the principles of gene mapping, discusses its relevance to dermatologists, and lists the established loci of dermatologically important genes.
We have constructed a primary genetic map spanning most of human chromosome 13. A total of 14 polymorphic DNA sequences and one protein polymorphism provided, after construction of haplotypes, seven markers for the long arm of this chromosome. A panel of cell lines from 30 three-generation families with large sibship size served as the sample set. Pairwise cross analysis of the inheritance patterns of the marker loci established that six of the seven loci constituted a single linkage group; the seventh was localized by physical means. Significantly higher recombination rates were found in female than in male meioses in several intervals. The six closely linked loci were arranged, based on the two-point data, in three clusters, and a number of alternate gene orders were excluded by three-point linkage tests. The order and spacing of the individual loci were refined by linkage analyses that considered five loci jointly.
Genetic loci for autosomal dominant pure hereditary spastic paraplegia (ADPHSP) have been mapped to chromosomes 2p, 8q, 12q, 14q, and 15q. We undertook a genomewide linkage screen of a large family with ADPHSP, for which linkage at all previously identified ADPHSP loci was excluded. Analysis of markers on chromosome 19q gave a peak pairwise LOD score of 3.72 at D19S420, allowing assignment of a novel ADPHSP locus (which we have termed "SPG12") to this region. Haplotype construction and analysis of recombination events narrowed the SPG12 locus to a 16.1-cM region between markers D19S868 and D19S902.
We recently described an autosomal dominant inclusion-body myopathy characterized by congenital joint contractures, external ophthalmoplegia, and predominantly proximal muscle weakness. A whole-genome scan, performed with 161 polymorphic markers and with DNA from 40 members of one family, indicated strong linkage for markers on chromosome 17p. After analyses with additional markers in the region and with DNA from eight additional family members, a maximum LOD score (Zmax) was detected for marker D17S1303 (Zmax=7.38; recombination fraction (theta)=0). Haplotype analyses showed that the locus (Genome Database locus name: IBM3) is flanked distally by marker D17S945 and proximally by marker D17S969. The positions of cytogenetically localized flanking markers suggest that the location of the IBM3 gene is in chromosome region 17p13.1. Radiation hybrid mapping showed that IBM3 is located in a 2-Mb chromosomal region and that the myosin heavy-chain (MHC) gene cluster, consisting of at least six genes, co-localizes to the same region. This localization raises the possibility that one of the MHC genes clustered in this region may be involved in this disorder.
The near-completion of the sequence for chromosome 22q revolutionizes map integration. We describe a sequence-based integrated map containing 968 loci including 516 known or predicted gene sequences, 317 STSs not included in these sequences, and 135 nonexpressed multinucleotide polymorphisms. The published sequence spans 34.6 Mb, inclusive of gaps estimated to total 1.1 Mb, compared with a top-down estimate of 43 Mb. This discrepancy is discussed, but will not be resolved until more of the genome is analyzed. The radiation hybrid map has 5% error in order and 34% error in location exceeding 1 Mb. The utility of a composite location based on evidence other than sequence is limited to regions not yet sequenced. A genetic map conditional on sequence order was constructed from pairwise lods. Its length of 74.8 cM in males and 80.2 cM in females is slightly less than the previous estimate not constrained by sequence order. Five recombination hot spots are detected, with differences in location between the sexes. Male recombination correlates with repetitive DNA, whereas female recombination does not. It remains to be seen whether this is true for other human chromosomes. An algorithm to improve the fit of cytogenetic bands sequence location reduces the discrepancies in cytogenetic assignment from 61 to 38. This sequence-based integrated map is represented in the genetic location database (LDB2000), which is available at http://cedar.genetics.soton.ac.uk/public_html/LDB2000.html.
We report the cDNA sequence of the zinc finger gene, ZNF195, which maps to chromosome 11p15.5. ZNF195 contains an N-terminal KRAB domain and 14 tandemly repeated Krüppel type zinc finger motifs at its C-terminus. Northern analysis shows expression of ZNF195 in adult heart, brain, placenta, skeletal muscle, and pancreas with a predominant transcript size of 4.3 kb. There is little expression in adult lung, liver, and kidney. In fetal lung, liver, kidney, and brain, the predominant transcript is 3.5 kb. Fetal brain also expresses a 4.3-kb transcript. RT-PCR analysis shows that two exons, 4a, which contains an inverted Alu sequence, and 4b, are differentially spliced and absent from the major transcript.
OBJECTIVE: The cocaine and amphetamine-regulated transcript (CART) is expressed in the brain of rodents and humans, and intracerebroventricular injection of the peptide in rats reduces food intake. The objective of the present study was to chromosomally map the CART gene and to examine the coding region of the gene for variability in obese subjects. METHODS: The coding region of the CART gene was analyzed by single-strand conformation polymorphism analysis in 84 subjects with early onset obesity. The prevalence of identified mutations was estimated in a cohort of 757 subjects with juvenile onset obesity [body mass index (BMI) = 35.7+/-5.7 kg/m2+/-standard deviation (S)] and in 890 random control subjects (BMI = 26.1+/-3.6 kg/m2+/-S). Furthermore, using radiation hybrid mapping we mapped the chromosomal localization of the human CART gene. RESULTS: Radiation hybrid mapping co-localized the CART gene with a recently published human obesity locus at chromosome 5q13-14 corresponding also to an obesity locus at the similar syntenic region in mice. We identified two silent polymorphisms in the 3'UTR region of the gene (position 1457 deletion of A and position 1475 A-->G substitution) and the prevalence of these was determined among obese and control subjects. However, none of the variants were associated with either obesity or weight gain during an average follow-up period of 27.4+/-8.4 years (S). CONCLUSION: Mutations in the coding region of the CART gene are unlikely to be involved in body weight control in Danish Caucasians with early onset obesity.
The gene for human complement component C9 has been mapped to chromosome 5. This was achieved by using a novel application of the polymerase chain reaction to amplify specifically the human C9 gene on a background of rodent DNA in somatic cell hybrids. The assignment to chromosome 5 was confirmed by in situ hybridization to human metaphase chromosomes, giving a regional localization of 5p13.
Complementary DNA encoding the human CYR61 protein was isolated from human embryonic tissues and mapped to chromosome 1p22-p31. We show that CYR61 encodes a 381 amino acid protein rich in cysteine and proline residues that is strongly conserved with the mouse homologue. Sequence analysis reveals the presence of several distinct protein domains which confer a mosaic structure to this protein and makes human CYR61 a member of a recently described growth regulator family that includes several proto-oncogene products. From our results we hypothesize that this new immediate early gene may play a role in cell commitment during embryogenesis and more generally in the control of cell proliferation.
The human PDGFA gene has been mapped previously to two different sites on chromosome 7 (7p21----p22 and 7q11.2----q21.1). Using in situ hybridization and human x mouse somatic cell hybrid lines we present data which confirm the localization of PDGFA to the terminal short arm of chromosome 7, at 7p22.
Fanconi anaemia (FA) is an autosomal recessive disorder characterized by progressive pancytopenia, short stature, radial ray defects, skin hyperpigmentation and a predisposition to cancer. Cells from FA patients are hypersensitive to cell killing and chromosome breakage induced by DNA cross-linking agents such as mitomycin C (MMC) and diepoxybutane (DEB). Consequently, the defect in FA is thought to be in DNA crosslink repair. Additional cellular phenotypes of FA include oxygen sensitivity, poor cell growth and a G2 cell cycle delay. At least 5 complementation groups for Fanconi anaemia exist, termed A through E. One of the five FA genes, FA(C), has been identified by cDNA complementation, but no other FA genes have been mapped or cloned until now. The strategy of cDNA complementation, which was successful for identifying the FA(C) gene has not yet been successful for cloning additional FA genes. The alternative approach of linkage analysis, followed by positional cloning, is hindered in FA by genetic heterogeneity and the lack of a simple assay for determining complementation groups. In contrast to genetic linkage studies, microcell mediated chromosome transfer utilizes functional complementation to identify the disease bearing chromosome. Here we report the successful use of this technique to map the gene for the rare FA complementation group D (FA(D)).