共查询到20条相似文献,搜索用时 15 毫秒
1.
Johanneson B McDonnell SK Karyadi DM Hebbring SJ Wang L Deutsch K McIntosh L Kwon EM Suuriniemi M Stanford JL Schaid DJ Ostrander EA Thibodeau SN 《Human genetics》2008,123(1):65-75
Genetic studies suggest that hereditary prostate cancer is a genetically heterogeneous disease with multiple contributing
loci. Studies of high-risk prostate cancer families selected for aggressive disease, analysis of large multigenerational families,
and a meta-analysis from the International Consortium for Prostate Cancer Genetics (ICPCG), all highlight chromosome 22q12.3
as a susceptibility locus with strong statistical significance. Recently, two publications have narrowed the 22q12.3 locus
to a 2.18 Mb interval using 54 high-risk families from the ICPCG collaboration, as defined by three recombination events on
either side of the locus. In this paper, we present the results from fine mapping studies at 22q12.3 using both haplotype
and recombination data from 42 high-risk families contributed from the Mayo Clinic and the Prostate Cancer Genetic Research
Study (PROGRESS) mapping studies. No clear consensus interval is present when all families are used. However, in the subset
of 14 families with ≥5 affected men per family, a 2.53-Mb shared consensus segment that overlaps with the previously published
interval is identified. Combining these results with data from the earlier ICPCG study reduces the three-recombination interval
at 22q12.3 to approximately 1.36 Mb.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
2.
Siqun L. Zheng Jianfeng Xu Sarah D. Isaacs Kathy Wiley Bao-li Chang Eugene R. Bleecker Patrick C. Walsh Jeffrey M. Trent Deborah A. Meyers William B. Isaacs 《Human genetics》2001,108(5):430-435
Prostate cancer is the most common malignancy diagnosed in men in the US. Genetic susceptibility to prostate cancer has been well documented. A region at chromosome 20q13 (HPC20) has been reported to be linked to a prostate cancer susceptibility gene. To confirm this finding, we genotyped 16 markers spanning approximately 95 cM on chromosome 20 in 159 hereditary prostate cancer (HPC) families. Positive (but not statistically significant) linkage scores were observed from 20pter to 20q11, with the highest non-parametric linkage (NPL) score for the complete dataset of 1.02 (P=0.15) being observed at D20S195 at 20q11. Evidence for linkage from parametric analyses with a dominant or a recessive model was weak. Interestingly, consistent with the original findings of linkage to 20 g higher linkage scores were observed in the subsets of families with a later age at diagnosis (> or =65 years; n=80, NPL=1.94, P=0.029 at D20S186), fewer than five affected family members (n=69, NPL=1.74, P=0.037 at D20S889), or without male-to-male disease transmission (n=60, NPL=1.01, P=0.15 at D20S117). The region with positive linkage scores spanned approximately 60 cM from 20pter to 20q11 in these subsets of families. Our results are consistent with a prostate cancer susceptibility locus on chromosome 20. 相似文献
3.
Mariano Rocchi Nicoletta Archidiacono Giovanni Romeo Marco Saginati Luciano Zardi 《Human genetics》1991,86(6):621-623
Summary Tenascin (TN) is a hexameric extracellular matrix glycoprotein that is highly expressed in solid tumors but has a restricted distribution in normal adult tissues. Each TN subunit is composed of segments with high homology to the sequences of epidermal growth factor, fibronectin and fibrinogen. Furthermore, it has been suggested that TN could modulate epithelial-mesenchymal and neuronal-glial interactions. Here, using a cDNA probe to human TN, we have carried out Southern blot analysis of the genomic DNAs from a panel of human-hamster somatic cell hybrids carrying different complements of human chromosomes. The results demonstrate that the human TN gene is located on chromosome 9. Furthermore, in situ hybridization studies demonstrate that human TN is located at 9q32–q34. 相似文献
4.
F. Stögbauer Peter Young Vincent Timmerman Petra Spoelders E. Bernd Ringelstein Christine Van Broeckhoven Gerd Kurlemann 《Human genetics》1997,99(5):685-687
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal neuropathy characterized by episodes of painful
brachial plexus neuropathy with muscle weakness and atrophy, as well as sensory disturbances. Single episodes are commonly
preceded by unspecific infections or immunization, or are associated with parturition. Minor facial dysmorphic features are
present in some pedigrees but do not clearly segregate with the disease. To confirm the recently described HNA locus on distal
chromosome 17q, we performed a genetic linkage study in an extended Turkish pedigree. We were able to refine the HNA locus
on chromosome 17q24–q25 in a 16-cM region.
Received: 21 October 1996 相似文献
5.
Mustapha M Chouery E Torchard-Pagnez D Nouaille S Khrais A Sayegh FN Mégarbané A Loiselet J Lathrop M Petit C Weil D 《Human genetics》2002,110(4):348-350
Usher syndrome (USH) is an autosomal recessive disorder associated with sensorineural hearing impairment and progressive visual loss attributable to retinitis pigmentosa. This syndrome is both clinically and genetically heterogeneous. Three clinical types have been described of which type I (USH1) is the most severe. Six USH1 loci have been identified. We report a Palestinian consanguineous family from Jordan with three affected children. In view of the combination of profound hearing loss, vestibular dysfunction, and retinitis pigmentosa in the patients, we classified the disease as USH1. Linkage analysis excluded the involvement of any of the known USH1 loci. A genome-wide screening allowed us to map this novel locus, USH1G, in a 23-cM interval on chromosome 17q24-25. The USH1G interval overlaps the intervals for two dominant forms of isolated hearing loss, namely DFNA20 and DFNA26. Since several examples have been reported of syndromic and isolated forms of deafness being allelic, USH1G, DFNA20, and DFNA26 might result from alterations of the same gene. Finally, a mouse mutant, jackson shaker ( js), with deafness and circling behavior has been mapped to the murine homologous region on chromosome 11. 相似文献
6.
Assignment of the gene for carboxypeptidase A to human chromosome 7q22→qter and to mouse chromosome 6 总被引:4,自引:0,他引:4
Honey N. K. Sakaguchi A. Y. Lalley P. A. Quinto C. Rutter W. J. Naylor S. L. 《Human genetics》1986,72(1):27-31
Summary A rat cDNA probe for preprocarboxypeptidase A was used to follow the segregation of the human gene for carboxypeptidase A (CPA) in 49 human x mouse somatic cell hybrids using Southern filter hybridization techniques. CPA was assigned to human chromosome 7q22qter. Similarly, the probe was used to follow the segregation of the mouse gene for carboxypeptidase A (Cpa) in 19 mouse x Chinese hamster somatic cell hybrids. Cpa was assigned to mouse chromosome 6. The gene for carboxypeptidase A forms part of a syntenic group that is conserved in man and mouse.Preliminary chromosomal assignments of carboxypeptidase A in man and mouse have been made in abstract (Honey et al. 1983a, b) 相似文献
7.
Localization of the gene for human erythrocyte glycophorin C to chromosome 2, q14–q21 总被引:2,自引:0,他引:2
Summary A complementary cDNA clone (900 bp) representing the 3 untranslated region and almost the entire coding sequence of the human erythrocyte membrane glycophorin C has been used to determine the chromosomal location of the blood group Gerbich locus by in situ hybridization. The results indicate that this locus is assigned to the region q14–q21 of chromosome 2. 相似文献
8.
Robert S. Sparkes Hiroyuki Sasaki T. Mohandas Katsuji Yoshioka Ivana Klisak Yoshiyuki Sakaki Camilla Heinzmann Melvin I. Simon 《Human genetics》1987,75(2):151-154
Summary The assignment of the human prealbumin (PALB) gene to chromosome region 18q11–q12.1 has been achieved using a human genomic probe in the study of human-mouse somatic cell hybrids and by in situ hybridization. Because familial amyloidotic polyneuropathy was reported previously to be due to a mutation in prealbumin, it can be inferred that the gene for this disorder also maps to 18q11.2–q12.1. 相似文献
9.
Mapping of a gene for epidermolytic palmoplantar keratoderma to the region of the acidic keratin gene cluster at 17q12–q21 总被引:9,自引:0,他引:9
Summary Epidermolytic palmoplantar keratoderma (EPPK) (Vörner-Unna-Thost) is an autosomal dominantly inherited skin disease of unknown etiology characterized by diffuse severe hyperkeratosis of the palms and soles and, histologically, by cellular degeneration. We have mapped a gene for EPPK to chromosome 17q11–q23, with linkage analysis using microsatellite DNA-polymorphisms, in a single large family of 7 generations. A maximum lod score of z=6.66 was obtained with the probe D17S579 at a recombination fraction of =0.00. This locus maps to the same region as the type I (acidic) keratin gene cluster. Keratins, members of the intermediate filament family, the major proteins of the cytoskeleton in epidermis, are differentially expressed in a tissue-specific manner. One acidic keratin, keratin 9 (KRT9), is expressed only in the terminally differentiated epidermis of palms and soles. The KRT9 gene has not yet been cloned; however, since the genes for most acidic keratins are clustered, it is highly probable that it too will map to this region. We therefore propose KRT9 as the candidate gene for EPPK. 相似文献
10.
Gerstmann-Str?ussler-Scheinker syndrome (GSS) is a human transmissible spongiform encephalopathy recently linked to the human analog of the prion protein gene (PRNP) on chromosome 20p. We have studied a large German GSS family for linkage to PRNP and have obtained a peak lod score of 1.15 at a recombination fraction (theta) of 0.00. This result provides additional evidence that GSS is linked to a mutation in codon 102 of the PRNP gene. Combining our data with linkage data previously reported yields a peak lod score of 4.52 at theta = 0.0. No evidence for linkage heterogeneity was found in the combined data set. 相似文献
11.
Lange EM Robbins CM Gillanders EM Zheng SL Xu J Wang Y White KA Chang BL Ho LA Trent JM Carpten JD Isaacs WB Cooney KA 《Human genetics》2007,121(1):49-55
Prostate cancer linkage studies have suggested the existence of a prostate cancer susceptibility gene on chromosome 17q21–22.
We now report the results of an extended linkage analysis including 95 new multiplex prostate cancer families and 9 additional
microsatellite markers resulting in a maximum LOD score of 2.99 at approximately 81–82 cM for all 453 pedigrees. Results from
these 95 new pedigrees provide additional support for a chromosome 17q21–22 prostate cancer susceptibility gene. Inclusion
of the 9 additional markers significantly reduced the size of the candidate region, as defined using a 1-LOD support interval,
especially when focusing analyses on subsets of pedigrees with four or more confirmed affecteds or average age of diagnosis
less than or equal to 65 years. A novel subset analysis of only those families (n = 147) that had four or more prostate cancer cases and an average age of prostate cancer diagnosis ≤ 65 years results in
a maximum LOD score of 5.49 at 78 cM with a 1-LOD support interval of 10 cM. This large set of pedigrees with four more prostate
cancer cases characterized by early-onset disease will serve as a useful resource for identifying the putative 17q21–22 prostate
cancer susceptibility gene. 相似文献
12.
Summary The human gene encoding the -polypeptide of propionyl-CoA carboxylase (PCC) has hitherto been localized to the distal half of the long arm of chromosome 13, segment 13q22q34. We studied the enzyme activities of mitochondrial carboxylases in cell cultures obtained from patients with different deletions of chromosome 13. By setting the PCC activity in normal diploid cell cultures (control group) at 100%, cell cultures with trisomy 13 showed 150% activity. In contrast, one of four patients with partial monosomy 13 had an enzyme activity of only 50%. Thus, by comparative deletion mapping, combined with studies of the gene-dosage effect, we have been able to assign the PCCA gene locus to chromosome band 13q32. 相似文献
13.
Adelina A. Davies Stephen E. Moss Mark R. Crompton Tania A. Jones Nigel K. Spurr Denise Sheer Christine Kozak Michael J. Crumpton 《Human genetics》1989,82(3):234-238
Summary The gene encoding a tissue inhibitor of metalloproteinases, TIMP, has previously been shown to be X-linked in both the human and mouse genomes. We have used a series of somatic cell hybrids segregating translocation and deletion X chromosomes to map the TIMP gene on the human X chromosome. In combination with previous data, the gene can be assigned to Xp11.23Xp11.4. Genetic linkage analyses demonstrate that TIMP is linked to the more distal ornithine transcarbamylase (OTC) locus at a distance of about 22 centimorgans. The data are consistent with the conclusion that TIMP maps to a conserved synteny and linkage group on the proximal short arm of the human X chromosome and on the pericentric region of the mouse X chromosome, including loci for synapsin-1, a member of the raf oncogene family, OTC, and TIMP. 相似文献
14.
Gough S 《Trends in molecular medicine》2004,10(7):302-305
Genetic studies have identified the HLA and CTLA4 regions as susceptibility loci for the development of common autoimmune thyroid diseases (AITDs), including Graves' disease and autoimmune hypothyroidism. Despite numerous studies, the identification of a third locus has remained elusive. Genetic-linkage studies have implicated chromosome 8q24 as a susceptibility locus for AITD. The gene encoding thyroglobulin (Tg), which encodes a major thyroid autoantigen, maps to this region, and a recent study has reported the association of several exonic single-nucleotide polymorphisms (SNPs) with disease. Although these preliminary data are potentially exciting, caution needs to be exercised, and replication of the data sought before Tg can be designated as the third locus for AITD. 相似文献
15.
Assignment of the gene coding for human β-glucocerebrosidase to the region q21-q31 of chromosome 1 using monoclonal antibodies 总被引:5,自引:0,他引:5
R. A. Barneveld W. Keiizer F. P. W. Tegelaers E. I. Ginns A. Geurts van Kessel R. O. Brady J. A. Barranger J. M. Tager H. Galjaard A. Westerveld A. J. J. Reuser 《Human genetics》1983,64(3):227-231
A series of man-Chinese hamster somatic cell hybrids with a variable content of human chromosomes was used to study the localization of the human gene coding for the lysosomal enzyme beta-glucocerebrosidase (EC 3.2.1.45). In lysates made from hybrid cells, the human enzyme was specifically recognized by a mouse monoclonal antibody raised against human placental beta-glucocerebrosidase. This monoclonal antibody did not cross-react with Chinese hamster beta-glucocerebrosidase. After reaction of the antibody with the enzyme, beta-glucocerebrosidase was precipitated by addition of Protein A-Sepharose beads, and was detected on the beads by its enzymatic activity. From the analysis of a series of man-Chinese hamster hybrids, among which were hybrids with specific segments of chromosome 1, we conclude that the gene coding for human beta-glucocerebrosidase is localized in the region q21-q31 of chromosome 1. 相似文献
16.
Summary Among several established mouse, rat, and Chinese hamster cell lines that were screened for cystathionine -synthase (CBS) activity, mouse 3T3 and Chinese hamster Don fibroblasts were found to contain no detectable activity. Somatic cell hybrids between human fibroblasts KG-7 with normal CBS activity and Don/a23TK- cells (series XXI) were examined for CBS activity and for human chromosome content. Only chromosome 21 cosegregated with CBS activity. Because the activities measured could represent either Chinese hamster or human gene products, we have prepared a new series of hybrids between Don/a23TK- cells and mutant human fibroblasts from a patient with homocystinuria due to deficiency of functional CBS mRNA. None of these (series XXV) hybrids contained detectable CBS activity, although collectively all human chromosomes were represented. Our results suggest that the human gene for CBS, called CBS, and thus for the most common form of homocystinuria, is located on chromosome 21. 相似文献
17.
Takahashi M Rapley E Biggs PJ Lakhani SR Cooke D Hansen J Blair E Hofmann B Siebert R Turner G Evans DG Schrander-Stumpel C Beemer FA van Vloten WA Breuning MH van den Ouweland A Halley D Delpech B Cleveland M Leigh I Chapman P Burn J Hohl D Görög JP Seal S Mangion J 《Human genetics》2000,106(1):58-65
Familial cylindromatosis is an autosomal dominant predisposition to multiple neoplasms of the skin appendages. The susceptibility gene has previously been mapped to chromosome 16q12-q13 and has features of a recessive oncogene/tumour suppressor gene. We have now evaluated 19 families with this disease by a combination of genetic linkage analysis and loss of heterozygosity in cylindromas from affected individuals. All 15 informative families show linkage to this locus, providing no evidence for genetic heterogeneity. Recombinant mapping has placed the gene in an interval of approximately 1 Mb. There is no evidence, between families, of haplotype sharing that might be indicative of common founder mutations. 相似文献
18.
Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1 → q22.3 in a patient with tyrosinemia type II 总被引:5,自引:0,他引:5
Ernst Natt Eva-Maria Westphal Su Ellen Toth-Fejel R. Ellen Magenis Neil R. M. Buist Ruth Rettenmeier Gerd Scherer 《Human genetics》1987,77(4):352-358
Summary Tyrosinemia II is an autosomal-recessively inherited condition caused by deficiency in the liver-specific enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5). We have restudied a patient with typical symptoms of tyrosinemia II who in addition suffers from multiple congenital anomalies including severe mental retardation. Southern blot analysis using a human TAT cDNA probe revealed a complete deletion of both TAT alleles in the patient. Molecular and cytogenetic analysis of the patient and his family showed one deletion to be maternally inherited, extending over at least 27 kb and including the complete TAT structural gene, whereas loss of the second TAT allele results from a small de novo interstitial deletion, del 16 (pterq22.1::q22.3qter), in the paternally inherited chromosome 16. Three additional loci previously assigned to 16q22 were studied in our patient: haptoglobin (HP), lecithin: cholesterol acyltransferase (LCAT), and the metallothionein gene cluster MT1, MT2. Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome. 相似文献
19.
Sandal Niels N. Salentijn Elma M.J. Kleine Michael Cai Daguang Arens-de Reuver Marjon Van Druten Marco de Bock Theo S.M. Lange Wouter Steen Per Jung Christian Marcker Kjeld Stiekema Willem J. Klein-Lankhorst René M. 《Molecular breeding : new strategies in plant improvement》1997,3(6):471-480
Beet cyst nematode-resistant sugar beet plants, containing the Hs1pro-1 locus from Beta procumbens, show a female transmission frequency of the resistance of ca. 90%. Such plants often suffer from tumour formation on leaves and root systems, and from the occurrence of a so-called multi-top phenotype. With the aim of obtaining resistant sugar beet material lacking these negative traits, nematode-resistant plants with a reduced size of the chromosome segment of the wild beet that carries the Hs1pro-1 gene were selected from backcrosses between the resistant stocks B883 or AN1-65-2 and susceptible sugar beet (Beta vulgaris). Analysis of such plants, referred to as Sat-minus plants, showed that the transmission frequency of the resistance to subsequent generations had dropped dramatically to ca. 0.5%. The multi-top phenotype was still present in the newly selected material, indicating that improvement of the resistant sugar beet material by further backcrossing will be hard to achieve. Two of the selected resistant offspring plants were analysed at the molecular level. With the aid of AFLP markers it was found that the size of the alien chromosome segment had decreased to 35% and 17% of the original size, respectively. Surprisingly, both plants had lost the Hs1pro-1 nematode resistance gene that recently was isolated from the original introgression material. This shows that more than one gene conferring resistance must be present in the locus in B883 and AN1-65-2 carrying the resistance gene Hs1pro-1. 相似文献
20.
The apolipoprotein(a) gene resides on human chromosome 6q26–27, in close proximity to the homologous gene for plasminogen 总被引:10,自引:2,他引:10
Susan Lynn Frank Ivana Klisak Robert S. Sparkes T. Mohandas James E. Tomlinson John W. McLean Richard M. Lawn Aldons J. Lusis 《Human genetics》1988,79(4):352-356
Summary Apolipoprotein(a) [apo(a)], the glycoprotein associated with the lipoprotein(a) [Lp(a)] subfraction of plasma lipoproteins, has been shown to exhibit heritable molecular weight isoforms ranging from 400–700 kDa. Increased serum concentrations of Lp(a) correlate positively with the risk of atherosclerosis. Variations in Lp(a) plasma levels among individuals are inherited as a codominant quantitative trait. As part of an effect to define the basis of these variations and further clarify the expression of the protein, we have determined the chromosomal location of the human apo(a) gene. Blot hybridization analysis of DNA from a panel of mouse-human somatic cell hybrids with an apo(a) cDNA probe revealed a complex pattern of bands, all of which segregated with chromosome 6. In situ hybridization yielded a single peak of grain density located on chromosome 6q26–27. Apo(a) cDNA sequences exhibit striking homology to those of the plasma protease plasminogen, and, therefore, we have reexamined the chromosome assignment of the plasminogen gene. We conclude that both the apo(a) and plasminogen genes reside on human chromosome 6q22–27, consistent with a gene duplication mechanism for their evolutionary origin. The results are of significance for the genetic control of apo(a) expression and genetic influences predisposing to atherosclerosis. 相似文献