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1.
A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q. 总被引:11,自引:2,他引:9
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J Morissette G Ct J L Anctil M Plante M Amyot E Hon G E Trope J Weissenbach V Raymond 《American journal of human genetics》1995,56(6):1431-1442
Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after age 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed in 40 patients. Six subjects were also diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members > 35 years of age, except for three obligatory carriers. Key recombination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 相似文献
2.
Karin G. Michels-Rautenstrauss Christian Y. Mardin Wido M. Budde Thomas Liehr J. Polansky Thai Nguyen Vincent Timmerman C. Van Broeckhoven Gottfried O. H. Naumann Rudolf A. Pfeiffer B. W. Rautenstrauss 《Human genetics》1998,102(1):103-106
Autosomal dominant juvenile open angle glaucoma (JOAG) is an early-onset form of primary open angle glaucoma (POAG), which
has been linked to chromosome 1q21–q31. Recently, mutations in the trabecular meshwork inducible glucocorticoid response gene
(TIGR), one of the candidate genes mapped in this region, were identified in glaucoma patients of several families. We screened
for mutations of the TIGR gene in two German families with JOAG and in 100 unselected sporadic cases of POAG. In the first
family we identified a Pro370Leu mutation and in the second family a Gly367Arg mutation cosegregating with the glaucoma phenotype.
No pathogenic mutation was found in 100 sporadic cases but a Tyr347Tyr polymorphism was found in two patients. Furthermore,
fluorescence in situ hybridization (FISH) analysis was used to map a TIGR-specific yeast artificial chromosome to 1q24.3–q25.2.
Received: 19 June 1997 / Accepted: 12 August 1997 相似文献
3.
Ahmed Belmouden Marie F. Adam Stéphane Dupont de Dinechin Antoine P. Brézin Philippe Rigault Ilya Chumakov Jean-François Bach Henri-Jean Garchon 《Genomics》1997,39(3):348
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG,GLC1A,has been mapped to 1q21–q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced theGLC1Ainterval to a maximum of 3 cM, between theD1S452/NGA1/D1S210andNGA5loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between theD1S2851andD1S218loci and that includes 96 YAC clones and 48 STSs. The newGLC1Ainterval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of aNotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify theGLC1Agene. 相似文献
4.
The eukaryotic genome contains a putative ATPase gene family that encodes proteins with one or two highly conserved domain(s)
of approximately 230 amino acids. These proteins have diverse cellular functions and mutation in at least one member of the
family has been associated with human disease, while mutations in other family members are known to cause cell cycle defects
in yeast. Therefore it is of interest to map more family members and so we have localized PSMC5 (the thyroid hormone receptor-interacting protein, TRIP1) and PSMC3 (the Tat-binding protein, TBP1) to chromosomes 17q24– q25 and 11p12–p13, respectively. We also present the map position of
a probable PSMC3 processed pseudogene locus on chromosome 9p.
Received: 18 July 1996 相似文献
5.
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
6.
M K Wirtz J R Samples P L Kramer K Rust J R Topinka J Yount R D Koler T S Acott 《American journal of human genetics》1997,60(2):296-304
Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 相似文献
7.
Gerard D. Schellenberg Haydeh Payami Ellen M. Wijsman Harry T. Orr Katrina A. B. Goddard Leojean Anderson Ellen Nemens June A. White M. Elisa Alonso Melvyn J. Ball Jeffrey Kaye John C. Morris Helena Chui A. Dessa Sadovnick Leonard L. Heston George M. Martin Thomas D. Bird 《American journal of human genetics》1993,53(3):619-628
Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analyses were used, in 49 families with a mean age at onset ≥60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score ≤ –2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P < .02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset ≥60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 相似文献
8.
M. Montagna Olga Serova B. S. Sylla Marie-Geneviève Mattei Gilbert M. Lenoir 《Human genetics》1996,98(6):738-740
The h-PRL-1 gene codes for a new phosphotyrosine phosphatase that may play an important role in the control of basic cellular
processes such as cell growth and proliferation. Using the cDNA of the h-PRL-1 gene as a probe, we examined a somatic mouse
and hamster × human hybrid panel and found that chromosomes 1, 17 and 11 harbor sequences homologous to h-PRL-1. By in situ hybridization of metaphase spreads, subchromosomal localizations were determined at bands 1p35–p34, 17q12– q21 and 11q24–q25;
in addition, a faint signal was detected at 12q24. The chromosomal assignment of the genes homologous to h-PRL-1 will help
the investigation of its possible involvement in human diseases involving genetic alteration at these chromosomal regions.
Received: 12 June 1996 / Revised: 27 July 1996 相似文献
9.
The locus (RP1) for one form of autosomal dominant retinitis pigmentosa (adRP) was mapped on chromosome 8q11-q22 between
D8S589 and D8S285, which are about 8 cM apart, by linkage analysis in an extended family ascertained in the USA. We have studied
a multigeneration Australian family with adRP and found close linkage without recombination between the disease locus and
D8S591, D8S566, and D8S166 (Zmax = 1.137– 4.650 at θ = 0.00), all mapped in the region known to harbor RP1. Assuming that the mutation of the same gene is
responsible for the disease in both families, the analysis of multiply informative meioses in the American and Australian
families places the adRP locus between D8S601 and D8S285, which reduces the critical region to about 4 cM, corresponding to
approximately 4 Mb, which is completely covered by a yeast artificial chromosome contig assembled recently.
Received: 23 April 1996 / Accepted: 3 July 1996 相似文献
10.
Linkage analysis was performed on a large Danish family to refine the position of RP18, the locus for autosomal dominant retinitis
pigmentosa, mapped previously between D1S534 and D1S305 in chromosome 1p13–q21. We genotyped the family members for five microsatellite-type
DNA polymorphisms and mapped RP18 between D1S422 and D1S2858 to a region of less than 2 cM. No obvious candidate gene has
yet been assigned to the chromosomal interval defined here.
Received: 15 September 1997 / Accepted: 12 January 1998 相似文献
11.
M. H. van den Berg Arthur A. M Wilde E. O. Robles de Medina Henk Meyer J. L. M. C. Geelen Roselie J. E. Jongbloed Hein J. J. Wellens Joep P. M. Geraedts 《Human genetics》1997,100(3-4):356-361
The Romano Ward long QT syndrome (LQTS) has an autosomal dominant mode of inheritance. Patients suffer from syncopal attacks
often resulting in sudden cardiac death. The main diagnostic parameter is a prolonged QT(c) interval as judged by electro-cardiographic investigation. LQTS is a genetically heterogeneous disease with four loci having
been identified to date: chromosome 11p15.5 (LQT1), 7q35–36 (LQT2), 3p21–24 (LQT3) and 4q25–26 (LQT4). The corresponding genes
code for potassium channels KVLQT1 (LQT1)and HERG (LQT2) and the sodium channel SCN5A (LQT3). The KVLQT1 gene is characterized
by six transmembrane domains (S1– S6), a pore region situated between the S5 and S6 domains and a C-terminal domain accounting
for approximately 60% of the channel. This domain is thought to be co-associated with another protein, viz. minK (minimal
potassium channel). We have studied a Romano Ward family with several affected individuals showing a severe LQTS phenotype
(syncopes and occurrence of sudden death). Most affected individuals had considerable prolongations of QT(c). By using haplotyping with a set of markers covering the four LQT loci, strong linkage was established to the LQT1 locus,
whereas the other loci (LQT2, LQT3 and LQT4) could be excluded. Single-strand conformation polymorphism analysis and direct
sequencing were used to screen the KVLQT1 gene for mutations in the S1–S6 region, including the pore domain. We identified
a Gly-216-Arg substitution in the S6 transmembrane domain of KVLQT1. The mutation was present in all affected family members
but absent in normal control individuals, providing evidence that the mutated KVLQT1-gene product indeed caused LQTS in this
family. The mutated KVLQT1-gene product thus probably results in a dominant negative suppression of channel activity.
Received: 25 March 1997 / Accepted: 21 April 1997 相似文献
12.
Febrile seizures (FS) are common in children, and the incidence is 2–5% before the age of 5 years. A four-generation Chinese
family with autosomal dominant febrile seizure and epilepsy was studied by genome-wide linkage analysis. Significant linkage
was identified with markers on chromosome 3q26.2–26.33 with a maximum pairwise LOD score of >3.00. Fine mapping defined the
new genetic locus within a 10.7-Mb region between markers D3S3656 and D3S1232. A maximum multipoint LOD score of 5.27 was detected at marker D3S1565. A previously reported CLCN2 gene for epilepsy was excluded as the disease-causing gene in the family by mutational analysis of all exons and exon–intron
boundaries of CLCN2 and by haplotype analysis. Mutation analysis of KCNMB2 and KCNMB3, which were two potassium-channel genes in this linkage region, did not reveal a disease causing mutation. Our results identified
another novel locus on chromosome 3q26.2–26.33, and future studies of the candidate genes at the locus will identify a new
gene for combined FS and idiopathic epilepsies.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
X.-H. Dai, W.-W. Chen, and X. Wang contributed equally to this work. 相似文献
13.
D E Goldgar L A Cannon-Albright A Oliphant J H Ward G Linker J Swensen T D Tran P Fields P Uharriet M H Skolnick 《American journal of human genetics》1993,52(4):743-748
In this paper we present linkage results from the analysis of 18 Utah breast cancer kindreds, for three 17q markers. Four kindreds had LOD scores greater than 1.0 for at least one of the marker loci. One of these kindreds has a LOD score of 6.07 with D17S579, and we believe it to be the most informative 17q family reported to date. Among the kindreds which appear unlinked to 17q were an early-onset breast cancer family, a large breast-ovarian family, and a kindred with mixed age at onset. Analysis of individual recombinants in the linked families localizes the BRCA1 gene between THRA1 and D17S579 (Mfd188). A comparison of the Cancer and Steroid Hormone Study (CASH) model and a model which assumes a rare dominant susceptibility locus with low penetrance and no phenocopies stresses the difficulties in assessing linkage if the assumptions of the CASH model in terms of age at onset of breast cancer are not appropriate for the BRCA1 locus. A hypothetical breast cancer pedigree is used to calculate gene carrier probabilities under the CASH model, thereby illustrating some of our concerns regarding the use of this model to detect and exclude 17q linkage in breast cancer families. 相似文献
14.
Characterization of a cytogenetic 17q11.2 deletion in an NF1 patient with a contiguous gene syndrome
Paola Riva Pierangela Castorina Siranoush Manoukian Leda Dalprà Luisa Doneda Giuseppe Marini Johannes den Dunnen L. Larizza 《Human genetics》1996,98(6):646-650
We report on a rare patient screened as a putative carrier of a contiguous gene syndrome on the basis of a complex phenotype
characterized by sporadic neurofibromatosis type 1 (NF1), dysmorphism, mental retardation and severe skeletal anomalies. A
cytogenetically visible 17q11.2 deletion was detected in the patient’s karyotype by high-resolution banding and confirmed
by fluorescence in situ hybridization with yeast artificial chromosomes targeting the NF1 region. Analysis of the segregation
from parents to proband of 13 polymorphic DNA markers, either contiguous or contained within the NF1 gene, showed that the
patient is hemizygous at sites within the NF1 gene – the AAAT-Alu repeat in the 5′ region of intron 27b, the CA/GT microsatellite
in the 3′ region of intron 27b, and the CA/GT microsatellite in intron 38 – and at the extragenic D17S798 locus, distal to
the 3′ end of NF1. The patient may be an important resource in the identification of genes downstream of NF1 that may contribute
to some of his extra-NF1 clinical signs.
Received: 8 May 1996 / Revised: 17 June 1996 相似文献
15.
Isabella Mammi David E. Iles Dominique Smeets Maurizio Clementi R. Tenconi 《Human genetics》1996,98(3):317-320
We present the case of a patient affected with Williams syndrome (WS), who developed a suspected malignant hyperthermia (MH)
reaction to general anesthesia. The proximity to the WS region of the gene encoding the L-type voltage-gated calcium channel
α2/δ-subunit (CACNL2A) on 7q11.23–q21.1, previously shown to be closely linked to some forms of MH susceptibility, prompted
us to investigate whether this gene is deleted in WS. Linkage studies and fluorescence in situ hybridization analysis demonstrated
that the CACNL2A locus is localized outside the WS deleted region.
Received: 19 February 1996 / Revised: 16 March 1996 相似文献
16.
Plasma methylumbelliferyl tetra-N-acetylchitotetraoside hydrolase or chitinase (CHIT) might play a role in degrading the
chitin wall of some microorganisms. In about 6% of Caucasian people the enzyme shows pseudodeficiency (defined as very low
activity without apparent symptoms). We have mapped this locus by linkage analysis to the marker D1S306 (z = 4.00 at θ
M = F = 0.0) on chromosome 1q between the flanking markers D1S191 and D1S245 in the area of 1q31–1qter.
Received: 13 December 1996 / Accepted: 8 July 1997 相似文献
17.
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
18.
A novel human Type I procollagen C-proteinase enhancer protein-like gene, PCOLCE2, was identified by sequencing an EST in the primary open-angle glaucoma (POAG) region on 3q21. The total cDNA encoded a 415-amino-acid protein that has 43% identity to the Type I procollagen C-proteinase enhancer protein (PCOLCE1). PCOLCE2 contains two CUB domains, which are thought to be involved in protein-protein interactions, and an NTR module. PCOLCE2 message is expressed in the trabecular meshwork, lungs, heart, brain, liver, skeletal muscle, kidney, pancreas, and placenta as a 2-kb message. PCOLCE2, a 52-kDa protein, is expressed in the trabecular meshwork. A novel gene, PCOLCE2, has been identified and characterized. Based upon its homology with collagen-binding proteins, its expression in the trabecular meshwork, and its chromosome location, PCOLCE2 is a candidate gene for GLC1C. However, no coding sequence mutations were detected in PCOLCE2 in a POAG patient from the GLC1C family. 相似文献
19.
Shangzhi Huang H. Li Wilson H. Y. Lo Christine Fischer F. Vogel Zhuyu Baizhu Labu 《Human genetics》1997,100(5-6):620-623
The mutant in a family with autosomal-dominant spastic paresis in Northern Tibet was mapped by linkage analysis with several
microsatellite markers to a gene locus at 14q11.2–q24.3, an area to which a few mutants leading to a condition with similar
clinical signs have previously been mapped. The mutant observed in this pedigree probably arose de novo. Gene loci at 2p21–
p24 and 15q, which have been found for other pedigrees with dominant spastic paresis, were excluded. The data in this pedigree
do not contradict the hypothesis proposed by another group that there might be anticipation.
Received: 28 April 1997 / Accepted: 10 June 1997 相似文献
20.
YAC and cosmid FISH mapping of an unbalanced chromosomal translocation causing partial trisomy 21 and Down syndrome 总被引:3,自引:0,他引:3
M. Nadal M. Milà Melanie Pritchard Antonio Mur Josep Pujals Jean-Louis Blouin Stylianos E. Antonarakis Francesca Ballesta X. Estivill 《Human genetics》1996,98(4):460-466
Most cases of Down syndrome (DS) result from a supernumerary chromosome 21; however, there are rare cases in which DS is
due to partial trisomy of chromosome 21, involving various segments of the chromosome. The characterization of cases of DS
that are due to partial trisomy 21 allows the phenotype to be correlated with the genotype. We present a case with features
of DS and a partial trisomy of chromosome 21 inherited from a paternal balanced translocation involving chromosomes 13 and
21. Fluorescence in situ hybridization analysis using yeast artificial chromosome (YAC) probes mapped the breakpoint to 21q22.1,
within YAC 230E8, which contains markers CBR, D21S333 and D21S334. Further mapping using cosmids positioned the breakpoint
proximal to CBR. The patient was also monosomic for the distal portion of chromosome 13 (q33–qter). Many phenotypic features
of DS were present including hypotonia, flat occiput, flat facies, up-slanted palpebral fissures, epicanthic folds, flat nasal
bridge, macroglossia, open mouth, small ears and a heart murmur. This case further supports the contention that the majority
of the phenotypic features of DS map to 21q22–qter and further refines the location of some of them. In addition to the DS
phenotype, the patient had a prominent upper maxilla with protruding upper incisors, and low levels of the coagulation factors
VII and X, consistent with a syndrome resulting from monosomy 13q33–qter. Since some features overlap between the two syndromes,
including severe mental retardation, it is unclear to what extent monosmy for 13q33–qter, trisomy for 21q22.1–qter, or a combination
of both, contributed to the common features of the phenotype.
Received: 27 March 1996 / Revised: 15 May 1996 相似文献