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1.
Summary A neonate with clinical features of the 11q23 deletion syndrome was apparently mosaic with the dominant cell line showing deletion of the chromosomal segment 11q23.3 to 11qter. The presence of a few lymphocytes with a normal karyotype indicates post-zygotic deletion of chromosome 11. The mother and brother of the propositus show folate-sensitive fragility at band 11q23.3. This case indicates in vivo deletion at a folate-sensitive fragile site. 相似文献
2.
Kohno Takashi; Otsuka Toshiyuki; Inazawa Johji; Abe Tatsuo; Yokota Jun 《DNA research》1996,3(6):421-424
We have characterized the breakpoint junction of the homozygousdeletion at chromosome 2q33 in a small cell lung carcinoma cellline. Cloning and sequencing of the genomic regions surroundingthe breakpoint junction of the deletion revealed that the homozygousdeletion was caused by a simple interstitial deletion of a 220-kbsegment. An AT-dinucleotide of contributing germline sequenceswas overlapped at the junction. Since there were one or twonucleotide overlaps of germline sequences at breakpoint junctionsin all four cases of interstitial deletions analyzed to date,this may reflect a common mechanism underlying the occurrenceof chromosomal interstitial deletion. 相似文献
3.
Refinement of the Multiple Exostoses Locus (EXT2) to a 3-cM Interval on Chromosome 11 总被引:5,自引:2,他引:3 下载免费PDF全文
Wim Wuyts Sarvan Ramlakhan Wim Van Hul Jacqueline T. Hecht Ans M. W. van den Ouweland Wendy H. Raskind Floris C. Hofstede Edwin Reyniers Dan E. Wells Bert de Vries Ernest U. Conrad April Hill Dmitry Zalatayev Jean Weissenbach Michael J. Wagner Egbert Bakker Dicky J. J. Halley Patrick J. Willems 《American journal of human genetics》1995,57(2):382-387
Hereditary multiple exostoses (EXT) is an autosomal dominant skeletal disorder characterized by the formation of multiple exostoses on the long bones. EXT is genetically heterogeneous, with at least three loci involved: one (EXT1) in the Langer-Giedion region on 8q23-q24, a second (EXT2) in the pericentromeric region of chromosome 11, and a third (EXT3) on chromosome 19p. In this study, linkage analysis in seven extended EXT families, all linked to the EXT2 locus, refined the localization of the EXT2 gene to a 3-cM region flanked by D11S1355 and D11S1361/D11S554. This implies that the EXT2 gene is located at the short arm of chromosome 11, in band 11p11-p12. The refined localization of EXT2 excludes a number of putative candidate genes located in the pericentromeric region of chromosome 11 and facilitates the process of isolating the EXT2 gene. 相似文献
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5.
Localization of an Ataxia-Telangiectasia Gene to an −500-kb Interval on Chromosome 11q23.1: Linkage Analysis of 176 Families by an International Consortium 下载免费PDF全文
Ethan Lange Anna-Lise Borresen Xiaoguang Chen Luciana Chessa Sujata Chiplunkar Patrick Concannon Sugandha Dandekar Steven Gerken Kenneth Lange Teresa Liang Carmel McConville Jeff Polakow Oscar Porras Galit Rotman Ozden Sanal Sepideh Sheikhavandi Yosef Shiloh Eric Sobel Malcolm Taylor Milhan Telatar Sharon Teraoka Aslihan Tolun Nitin Udar Nancy Uhrhammer Lina Vanagaite Zhijun Wang Beth Wapelhorst Jocyndra Wright Huan-Ming Yang Lan Yang Yael Ziv Richard A. Gatti 《American journal of human genetics》1995,57(1):112-119
We describe a 20-point linkage analysis map of chromosome 11q22-23 that is based on genotyping 249 families (59 CEPH and 190 A-T). Monte Carlo linkage analyses of 176 ataxia-telangiectasia (A-T) families localizes the major A-T locus to the region between S1819(A4) and S1818(A2). When seven nonlinking families were excluded from subsequent analyses, a 2-lod support interval of ~500 kb was identified between S1819(A4) and S1294. No recombinants were observed between A-T and markers S384, B7, S535, or S1294. Only 17 of the international consortium families have been assigned to complementation groups. The available evidence favors either a cluster of A-T genes on chromosome 11 or intragenic defects in a single gene. 相似文献
6.
Co-localization of the ketohexokinase and glucokinase regulator genes to a 500-kb region of Chromosome 2p23 总被引:1,自引:0,他引:1
B. E. Hayward J. A. Fantes J. P. Warner S. Intody J. P. Leek A. F. Markham D. T. Bonthron 《Mammalian genome》1996,7(6):454-458
The glucokinase regulator (GCKR) is a 65-kDa protein that inhibits glucokinase (hexokinase IV) in liver and pancreatic islet.
The role of glucokinase (GCK) as pancreatic β cell glucose sensor and the finding of GCK mutations in maturity onset diabetes
of the young (MODY) suggest GCKR as a further candidate gene for type 2 diabetes. The inhibition of GCK by GCKR is relieved
by the binding of fructose-1-phosphate (F-1-P) to GCKR. F-1-P is the end product of ketohexokinase (KHK, fructokinase), which,
like GCK and GCKR, is present in both liver and pancreatic islet. KHK is the first enzyme of the specialized pathway that
catabolizes dietary fructose. We have isolated genomic clones containing the human GCKR and KHK genes. By fluorescent in situ hybridization (FISH), KHK maps to Chromosome (Chr) 2p23.2-23.3, a new assignment corroborated by somatic cell hybrid analysis.
The localization of GCKR, originally reported by others as 2p22.3, has been reassessed by high-resolution FISH, indicating
that, like KHK, GCKR maps to 2p23.2-23.3. The proximity of GCKR and KHK was further demonstrated both by two-color interphase
FISH, which suggests that the two genes lie within 500 kb of each other, and by analysis of overlapping YAC and P1 clones
spanning the interval between GCKR and KHK. A new microsatellite polymorphism was used to place the GCKR-KHK locus between
D2S305 and D2S165 on the genetic map. The co-localization of these two metabolically connected genes has implications for the interpretation
of linkage or allele association studies in type 2 diabetes. It also raises the possibility of coordinate regulation of GCKR
and KHK by common cis-acting regulatory elements.
Received: 8 December 1995 / Accepted: 27 January 1996 相似文献
7.
Farook VS Puppala S Schneider J Fowler SP Chittoor G Dyer TD Allayee H Cole SA Arya R Black MH Curran JE Almasy L Buchanan TA Jenkinson CP Lehman DM Watanabe RM Blangero J Duggirala R 《Obesity (Silver Spring, Md.)》2012,20(10):2083-2092
The prevalence of metabolic syndrome (MS) has been rising alarmingly worldwide, including in the United States, but knowledge on specific genetic determinants of MS is very limited. Therefore, we planned to identify the genetic determinants of MS as defined by National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII) criteria. We performed linkage screen for MS using data from 692 Mexican Americans, who participated in the San Antonio Family Diabetes/Gallbladder Study (SAFDGS). We found strong evidence for linkage of MS on chromosome 7q (LOD = 3.6, empirical P = 6.0 × 10(-5)), between markers D7S2212 and D7S821. In addition, six chromosomal regions exhibited potential evidence for linkage (LOD ≥1.2) with MS. Furthermore, we examined 29 single-nucleotide polymorphisms (SNPs) from the fatty acid translocase (FAT or CD36, 18 SNPs) gene and guanine nucleotide binding protein, α transducing 3 (GNAT3, 11 SNPs) gene, located within the 1-LOD support interval region for their association with MS and its related traits. Several SNPs were associated with MS and its related traits. Remarkably, rs11760281 in GNAT3 and rs1194197 near CD36 exhibited the strongest associations with MS (P = 0.0003, relative risk (RR) = 1.6 and P = 0.004, RR = 1.7, respectively) and several other related traits. These two variants explained ~18% of the MS linkage evidence on chromosome 7q21, and together conferred approximately threefold increase in MS risk (RR = 2.7). In conclusion, our linkage and subsequent association studies implicate a region on chromosome 7q21 to influence MS in Mexican Americans. 相似文献
8.
Conductin or Axil, an Axin homolog, plays an important role in the regulation of β-catenin stability in the Wnt signaling pathway. To facilitate the molecular analysis of the human gene, we isolated the human homolog, AXIN2. The cDNA contains a 2529-bp open reading frame and encodes a putative protein of 843 amino acids. Compared with rat and mouse homologs, AXIN2 shows an overall 89% amino acid identity. Several functional domains in this protein are highly conserved including the GRS (95.9%), GSK-3β (96.3%), Dsh (98%), and β-catenin (89.9%) domains. Radiation hybrid mapping localized the AXIN2 gene to human chromosome 17q23–q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Human AXIN2 is thus a very strong candidate involved in multiple tumor types. 相似文献
9.
Kathryn L. Evans John Brown Yoshiro Shibasaki Rebecca S. Devon Lin He Benoit Arveiler Sheila Christie John C. Maule David Baillie Euan M. Slorach Susan M. Anderson John R. Gosden Joelle Petit Andreas Weith Christine M. Gosden Douglas H. R. Blackwood David M. St. Clair Walter J. Muir Anthony J. Brookes David J. Porteous 《Genomics》1995,28(3)
Forty-nine clones derived by microdissection of a schizophrenia-associated t(1;11)(q42.1;q14.3) breakpoint region have been assigned by somatic cell hybrid mapping to seven discrete intervals on the long arm of human chromosome 11. Eleven of the clones were shown to map to a small region immediately distal to the translocation breakpoint on 11q.A 3-Mb contiguous clone map of this region was established by isolation of corresponding YAC recombinants. The contig was oriented and shown to traverse the translocation breakpoint by FISH and microsatellite marker analysis. This contig will facilitate the isolation of candidate sequences whose expression may be affected by the translocation. 相似文献
10.
David A. Good Frances Busfield Barbara H. Fletcher David L. Duffy Janine B. Kesting John Andersen Joanne T. E. Shaw 《American journal of human genetics》2002,70(2):517-525
Paget disease of bone (PDB) is characterized by increased osteoclast activity and localized abnormal bone remodeling. PDB has a significant genetic component, with evidence of linkage to chromosomes 6p21.3 (PDB1) and 18q21-22 (PDB2) in some pedigrees. There is evidence of genetic heterogeneity, with other pedigrees showing negative linkage to these regions. TNFRSF11A, a gene that is essential for osteoclast formation and that encodes receptor activator of nuclear factor-kappa B (RANK), has been mapped to the PDB2 region. TNFRSF11A mutations that segregate in pedigrees with either familial expansile osteolysis or familial PDB have been identified; however, linkage studies and mutation screening have excluded the involvement of RANK in the majority of patients with PDB. We have excluded linkage, both to PDB1 and to PDB2, in a large multigenerational pedigree with multiple family members affected by PDB. We have conducted a genomewide scan of this pedigree, followed by fine mapping and multipoint analysis in regions of interest. The peak two-point LOD scores from the genomewide scan were 2.75, at D7S507, and 1.76, at D18S70. Multipoint and haplotype analysis of markers flanking D7S507 did not support linkage to this region. Haplotype analysis of markers flanking D18S70 demonstrated a haplotype segregating with PDB in a large subpedigree. This subpedigree had a significantly lower age at diagnosis than the rest of the pedigree (51.2+/-8.5 vs. 64.2+/-9.7 years; P=.0012). Linkage analysis of this subpedigree demonstrated a peak two-point LOD score of 4.23, at marker D18S1390 (straight theta=0), and a peak multipoint LOD score of 4.71, at marker D18S70. Our data are consistent with genetic heterogeneity within the pedigree and indicate that 18q23 harbors a novel susceptibility gene for PDB. 相似文献
11.
Mapping of a Gene for Long QT Syndrome to Chromosome 4q25-27 总被引:21,自引:0,他引:21
Jean-Jacques Schott Flavien Charpentier Sophie Peltier Patrick Foley Emmanuel Drouin Jean-Brieuc Bouhour Patricia Donnelly Gilles Vergnaud Lucien Bachner Jean-Paul Moisan Herv Le Marec Olivier Pascal 《American journal of human genetics》1995,57(5):1114-1122
Long QT syndrome (LQTS) is a heterogeneous inherited disorder causing syncope and sudden death from ventricular arrhythmias. A first locus for this disorder was mapped to chromosome 11p15.5. However, locus heterogeneity has been demonstrated in several families, and two other loci have recently been located on chromosomes 7q35-36 and 3p21-24. We used linkage analysis to map the locus in a 65-member family in which LQTS was associated with more marked sinus bradycardia than usual, leading to sinus node dysfunction. Linkage to chromosome 11p15.5, 7q35-36, or 3p21-24 was excluded. Positive linkage was obtained for markers located on chromosome 4q25-27. A maximal LOD score of 7.05 was found for marker D4S402. The identification of a fourth locus for LQTS confirms its genetic heterogeneity. Locus 4q25-27 is associated with a peculiar phenotype within the LQTS entity. 相似文献
12.
Ralf Sudbrak Vincent Procaccio Monica Klausnitzer Julie L. Curran Koen Monsieurs Christine Van Broeckhoven Richard Ellis Luc Heyetens Edmund J. Hartung Geneviéve Kozak-Ribbens Dorit Heilinger Jean Weissenbach Frank Lehman-Horn Clemens R. Mueller Thomas Deufel Alistair D. Stewart Jo?l Lunardi 《American journal of human genetics》1995,56(3):684-691
Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disease for which MH susceptibility (MHS) is transmitted as an autosomal dominant trait. A potentially life-threatening MH crisis is triggered by exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. The first malignant hyperthermia susceptibility locus (MHS1) was identified on human chromosome 19q13.1, and evidence has been obtained that defects in the gene for the calcium-release channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor; RYR1) can cause some forms of MH. However, MH has been shown to be genetically heterogeneous, and additional loci on chromosomes 17q and 7q have been suggested. In a collaborative search of the human genome with polymorphic microsatellite markers, we now found linkage of the MHS phenotype, as assessed by the European in vitro contracture test protocol, to markers defining a 1-cM interval on chromosome 3q13.1. A maximum multipoint lod score of 3.22 was obtained in a single German pedigree with classical MH, and none of the other pedigrees investigated in this study showed linkage to this region. Linkage to both MHS1/RYR1 and putative loci on chromosome 17q and 7q were excluded. This study supports the view that considerable genetic heterogeneity exists in MH. 相似文献
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14.
Molecular characterization of a 130-kb terminal microdeletion at 22q in a child with mild mental retardation. 总被引:16,自引:2,他引:14 下载免费PDF全文
A C Wong Y Ning J Flint K Clark J P Dumanski D H Ledbetter H E McDermid 《American journal of human genetics》1997,60(1):113-120
We have analyzed a recently described 22q13.3 microdeletion in a child with some overlapping features of the cytologically visible 22q13.3 deletion syndrome. Patient NT, who shows mild mental retardation and delay of expressive speech, was previously found to have a paternal microdeletion in the subtelomeric region of 22q. In order to characterize this abnormality further, we have constructed a cosmid/P1 contig covering the terminal 150 kb of 22q, which encompasses the 130-kb microdeletion. The microdeletion breakpoint is within the VNTR locus D22S163. The cloning of the breakpoint sequence revealed that the broken chromosome end was healed by the addition of telomeric repeats, indicating that the microdeletion is terminal. This is the first cloned terminal deletion breakpoint on a human chromosome other than 16p. The cosmid/P1 contig was mapped by pulsed-field gel electrophoresis analysis to within 120 kb of the arylsulfatase A gene, which places the contig in relation to genetic and physical maps of the chromosome. The acrosin gene maps within the microdeletion, approximately 70 kb from the telomere. With the distal end of chromosome 22q cloned, it is now possible to isolate genes that may be involved in the overlapping phenotype of this microdeletion and 22q13.3 deletion syndrome. 相似文献
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16.
D García-Cruz L García-Esquivel H Rivera G Vaca A Rolón J M Cantú 《Annales de génétique》1985,28(3):193-196
A 10 10/12-year-old boy with a de novo t(11;15)(q25;q23) leading to trisomy 15q23----qter was studied. The clinical features were compatible with other cases of distal trisomy 15q. The critical segment for this trisomy is tentatively assigned to bands 15q25----qter. 相似文献
17.
Hongyan Chen Bing Sun Yingjie Zhao Xiao Song Weiwei Fan Keke Zhou Liangfu Zhou Ying Mao Daru Lu 《PloS one》2012,7(12)
Background
A single nucleotide polymorphism (SNP) at locus 11q23.3 (rs498872) in the near 5′-UTR of the PHLDB1 gene was recently implicated as a risk factor for gliomas in a genome-wide association study, and this involvement was confirmed in three additional studies.Methodology/Principal Findings
To identify possible causal variants in the region, the authors genotyped 15 tagging SNPs in the 200 kb genomic region at 11q23.3 locus in a Chinese Han population-based case-control study with 983 cases and 1024 controls. We found evidence for an association between two independent loci (both the PHLDB1 and the ACRN1 genes) and a predisposition for gliomas. Among the multiple significant SNPs in the PHLDB1 gene region, the rs17749 SNP was the most significant [P = 1.31×10−6 in a recessive genetic model]. Additionally, two novel SNPs (rs2236661 and rs494560) that were independent of rs17749 were significantly associated with glioma risk in a recessive genetic model [P = 1.31×10−5 and P = 3.32×10−5, respectively]. The second novel locus was within the ARCN1 gene, and it was associated with a significantly reduced risk for glioma.Conclusions/Significance
Our data strongly support PHLDB1 as a susceptibility gene for glioma, also shedding light on a new potentially candidate gene, ARCN1. 相似文献18.
Translocation (14;21)(q11;q22) in a woman with history of abortions and a child with Down's syndrome
A translocation (14;21)(q11;q22) was observed in a woman with history of abortions and in her child with Down's syndrome. This appears to be the first report of such a translocation with no centric fusion between the acrocentric chromosomes leading to a count of 45 chromosomes in the carrier and giving birth to a Down's syndrome child. 相似文献
19.
Elfride De Baere Yoshimitsu Fukushima Kent Small Nitin Udar Guy Van Camp Kristien Verhoeven Aarno Palotie Anne De Paepe Ludwine Messiaen 《Genomics》2000,68(3):296
The blepharophimosis syndrome (BPES) is a rare genetic disorder characterized by blepharophimosis, ptosis, epicanthus inversus, and telecanthus. In type I, BPES is associated with female infertility, while in type II, the eyelid defect occurs by itself. The BPES syndrome has been mapped to 3q23. Previously, we constructed a YAC-, PAC-, and cosmid-based physical map surrounding the 3q23 translocation breakpoint of a t(3;4)(q23;p15.2) BPES patient, containing a 110-kb PAC (169-C 10) and a 43-kb cosmid (11-L 10) spanning the breakpoint. In this report, we present the identification of BPESC1 (BPES candidate 1), a novel candidate gene that is disrupted by the translocation on chromosome 3. Cloning of the cDNA has been performed starting from a testis-specific EST, AI032396, found in cosmid 11-L 10. The cDNA sequence of BPESC1 is 3518 bp in size and contains an open reading frame of 351 bp. No significant similarities with known proteins have been found in the sequence databases. BPESC1 contains three exons and spans a genomic fragment of 17.5 kb. Expression of BPESC1 was observed in adult testis tissue. We performed mutation analysis in 28 unrelated familial and sporadic BPES patients, but, apart from the disruption by the translocation, found no other disease-causing mutations. These data make it unlikely that BPESC1 plays a major role in the pathogenesis of BPES. 相似文献
20.
Simon Baron-Cohen Laura Murphy Bhismadev Chakrabarti Ian Craig Uma Mallya Silvia Lakato?ová Karola Rehnstrom Leena Peltonen Sally Wheelwright Carrie Allison Simon E. Fisher Varun Warrier 《PloS one》2014,9(5)
Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10−5, 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10−6). In this analysis, one of the SNPs (rs789859) showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115) were nominally significant (lowest p-value 3.278 × 10−4). Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64). The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study. 相似文献