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1.
Meyer B Bazzi H Zidek V Musilova A Pravenec M Kurtz TW Nurnberg P Christiano AM 《Differentiation; research in biological diversity》2004,72(9-10):541-547
A recessive hairless mutation arose spontaneously in a congenic line of spontaneously hypertensive rats SHR.BN-(D1Mit3-Igf2)/Ipcv. The mutant rats develop generalized alopecia except for partial hair growth on their heads. Affected animals of the congenic line were crossed with LEW rats and randomly bred for several generations. A genome scan in 74 affected and 75 unaffected offspring localized the mutant gene on rat chromosome 18p12, near the marker D18Rat107, which is closely linked to the desmosomal cadherin gene cluster, syntenic to mouse chromosome 18 and human chromosome 18q12. Recently, the mouse and rat phenotypes lah/lah (lanceolate hair) and lah(J)/lah(J)(lanceolate hair-J) were found to be caused by mutations in the desmoglein 4 (Dsg4) gene. Direct sequencing of the Dsg4 gene in the SHR revealed a homozygous C-to-T transition generating a premature termination codon within exon 8 in the affected animals. Further studies on the skin histology in affected rats demonstrated features consistent with a lanceolate hair mutation, providing further support for the crucial role of desmoglein 4 in hair shaft differentiation. 相似文献
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We describe a family with severe progressive cerebellar ataxia involving the trunk, the extremities, and speech. The proband, who has prominent atrophy of the cerebellum, shown by magnetic resonance imaging, was confined to a wheelchair at the age of 44 years. Two sons have episodes of vertigo and ataxia that are not responsive to acetazolamide. Quantitative eye-movement testing showed a consistent pattern of abnormalities localizing to the cerebellum. Genotyping suggested linkage to chromosome 19p, and SSCP showed an aberrant migrating fragment in exon 6 of the calcium-channel gene CACNA1A, which cosegregated with the disease. Sequencing of exon 6 identified a G-->A transposition in one allele, at nucleotide 1152, resulting in a predicted glycine-to-arginine substitution at codon 293. The CAG-repeat expansion associated with spinocerebellar ataxia 6 was not present in any family members. This family is unique in having a non-CAG-repeat mutation that leads to severe progressive ataxia. Since a great deal is known about the function of calcium channels, we speculate on how this missense mutation leads to the combination of clinical symptoms and signs. 相似文献
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A missense mutation in the bovine MGF gene is associated with the roan phenotype in Belgian Blue and Shorthorn cattle 总被引:5,自引:0,他引:5
Jeffrey J. Seitz Sheila M. Schmutz Tracey D. Thue Fiona C. Buchanan 《Mammalian genome》1999,10(7):710-712
The Roan locus is responsible for the coat coloration of Belgian Blue and Shorthorn cattle. The solid-colored and white animals
are homozygotes, and the roan animals, with intermingled colored and white hairs, are heterozygous. The roan phenotype was
mapped to cattle Chromosome (Chr) 5 with microsatellites, and a candidate gene was proposed (Charlier et al. Mamm Genome 7,
138, 1996). PCR primers to the exons of this candidate gene, the steel locus or mast cell growth factor (MGF) were designed. Solid-colored and white animals were sequenced. A missense mutation at 654 bp (amino acid 193, Ala → Asp)
was detected in these two groups. A PCR-RFLP was designed to this single base pair change, and 143 animals in total (Belgian
Blue, Shorthorn, and various other breeds) were screened. In addition, the Canadian Beef Cattle Reference Herd (http://skyway.usask.ca/∼schmutz)
was used to verify Mendelian inheritance of this marker with the phenotypic inheritance of roan. Our data suggest that this
mutation in the bovine MGF gene is responsible for the roan phenotype.
Received: 10 December 1998 / Accepted: 26 February 1998 相似文献
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Blaszczyk WM Arning L Hoffmann KP Epplen JT 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2005,18(2):144-145
Tyrosinase serves as a key enzyme in the synthesis of melanin. In humans mutations in the TYR gene are associated with type 1 oculocutaneous albinism (OCA1) that leads to reduced or absent pigmentation of skin, hair and eye. Various mutations causing OCA in man, mouse, rabbit and cattle have been identified throughout the Tyrosinase gene including nonsense, missense, frameshift and splice site alterations. Here we report a missense substitution at codon R299H in exon 2 of the Tyr gene in the albino Wistar rat. As this very exchange has already been described in OCA patients, our findings reinforce the significance of this region for normal catalytic activity of tyrosinase protein. 相似文献
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Arginine-auxotrophic phenotype resulting from a mutation in the pryA gene of Escherichia coli B-r. 总被引:6,自引:3,他引:3 下载免费PDF全文
A Abd-el-Al 《Journal of bacteriology》1969,97(1):466-468
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A missense mutation in the VHYNP motif of a DELLA protein causes a semi-dwarf mutant phenotype in Brassica napus 总被引:2,自引:0,他引:2
Chao Liu Jilin Wang Tiandai Huang Fang Wang Fang Yuan Xiaomao Cheng Yan Zhang Shuwen Shi Jiangsheng Wu Kede Liu 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(2):249-258
Although dwarf genes have been widely used to improve lodging resistance and enhance harvest index in cereal crops, lodging is still a serious problem in rapeseed (Brassica napus) production. A semi-dwarf B. napus mutant, ds-1, was identified through EMS mutagenesis of a microspore-cultured DH line. The mutant had a significant reduction in height due to a lower first branch position and shorter internodes when compared with wild-type cultivars. This dwarfism was inherited as a single semi-dominant gene, ds-1. DS-1 locus was mapped to chromosome A6, and co-segregated with a microsatellite marker BnEMS1125 derived from the gene BnRGA. BnRGA encodes a DELLA protein that functions as a GA signaling repressor. The expression of a mutant BnRGA allele from ds-1, Bnrga-ds, caused dwarf phenotypes in Arabidopsis. Comparative sequencing of RGA open-reading frames (ORFs) of ds-1 and wild-type cultivars revealed a single proline (P)-to-leucine (L) substitution that may lead to a gain-of-function mutation in GA signaling. The expression of the Arabidopsis homolog, Atrga-ds, bearing this site-directed mutation also rendered dwarf phenotypes in Arabidopsis, which demonstrated that the P-to-L mutation in the VHYNP motif of Bnrga-ds is responsible for the dwarfism. A yeast two-hybrid assay confirmed that this mutation inhibited the interaction between Bnrga-ds/Atrga-ds and the GA receptor, AtGID1A, in the presence of GA3, suggesting that the conserved proline residue in the VHYNP motif of DELLA protein directly participates in DELLA-GID1 interaction. Identification and characterization of the dwarf gene ds-1 will facilitate its utilization in improving lodging resistance in Brassica breeding. 相似文献
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Buchbinder S Bärtsch U Müller M Zorn M Nawroth PP Schilling T 《Genetics and molecular research : GMR》2011,10(2):1042-1049
Mutations in the melanocortin-4 receptor (MC4R) are associated with severe obesity, independent of their effect on cortisol or thyroid-stimulating hormone levels. We examined a morbidly obese male (BMI = 62 kg/m2) with a binge-eating disorder and eight family members for mutations in the MC4R gene and potential differences in leptin levels. Fifty healthy individuals served as controls. Sequence analysis revealed a novel heterozygous missense mutation (c.302 C>A, p.T101N) located in the second transmembrane domain of the receptor, which was not detected in controls. The Fisher exact test revealed an association between the T101N mutation and history of obesity (P < 0.05) in the family. The Kruskal-Wallis test showed an association between the mutation and the leptin/BMI ratio (P < 0.05), while there was no association between the T101N mutation and diabetes or arterial hypertension in the family. Although the available family was small, we could show a significant association between the heterozygous T101N mutation and obesity. 相似文献
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Since the identification of the NF2 tumor suppressor gene in 1993, various mutations have been found in NF2-related tumors and in lymphocytes from NF2 patients. Most of the reported mutations result in truncated gene products. Missense mutations affecting the tumor suppressor are rare. These missense mutations would provide valuable information for the understanding of the function of the tumor suppressor, since they should affect critical parts of the protein. In this study we describe a novel point mutation in exon 15 of the NF2 gene, which is found in lymphocyte DNA of two NF2 patients from one family. This mutation is expected to result in a substitution of Pro for Gln at codon 538. Though both of the two patients developed bilateral vestibular schwannomas, the first patient showed onset of the disease at the age of 31 years and presented with various central, peripheral and abdominal tumors, while the second patient showed later onset of clinical symptoms (at age 52 years) and presented with only two additional small spinal tumors. 相似文献
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Marie Desgeorges Michel Rodier Michel Piot Jacques Demaille Mireille Claustres 《Human genetics》1995,96(6):717-720
We report molecular and clinical analyses in four unrelated patients with cystic fibrosis (CF) with compound heterozygosity for the L206W mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). This uncommon missense mutation (frequency less than 1% in a sample of 336 CF chromosomes from Southern France) replaces a leucine by a tryptophan residue in the middle of the third transmembrane domain of CFTR. On the basis of the clinical features presented by the four patients, we postulate that the L206W might be associated with pancreatic sufficiency and residual transmembrane transport of chloride in lung. 相似文献
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Duchesne A Gautier M Chadi S Grohs C Floriot S Gallard Y Caste G Ducos A Eggen A 《Genomics》2006,88(5):610-621
Syndactyly in Holstein cattle is an autosomal recessive abnormality characterized by the fusion of the functional digits. This disorder has been previously mapped to the telomeric part of bovine chromosome 15. Here, we describe the fine-mapping of syndactyly in Holstein cattle to a 3.5-Mb critical interval using a comparative mapping approach and an extended pedigree generated by embryo transfer. We report genetic evidence for the exclusion of two genes previously suggested as candidates (EXT2 and ALX4) and describe the identification of a doublet mutation in complete linkage disequilibrium with syndactyly in one gene of the critical interval: LRP4. Finally, based on recent discoveries concerning the mouse mutants dan and mdig and a mouse knockout for Lrp4, we present solid evidence that the subsequent substitution in LRP4 exon 33 is a strong candidate causal mutation for syndactyly in Holstein cattle. 相似文献
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The Drosophila dominant wing mutation Dichaete results from ectopic expression of a Sox-domain gene 总被引:1,自引:0,他引:1
Russell S 《Molecular & general genetics : MGG》2000,263(4):690-701
The dominant Drosophila wing mutation Dichaete is characterised by the deletion of proximal wing structures. By analysing a number of new Dichaete alleles, phenotypic revertants and enhancer piracy lines, we show that the wing phenotype results from ectopic expression
of the Sox-domain gene Dichaete. Ectopic expression of the Sox gene results in an increase in cell death in the proximal region of the wing imaginal disc and leads to alterations in the
normal expression of wingless. Since ectopic expression of wingless in the proximal region of the wing disc can rescue aspects of the Dichaete phenotype, it is likely that Dichaete specifically interferes with the establishment or maintenance of a critical domain of wingless expression in the wing disc.
Received: 20 January 2000 / Accepted: 14 February 2000 相似文献
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A double missense mutation in the ATM gene of a Dutch family with ataxia telangiectasia 总被引:1,自引:0,他引:1
M. J. van Belzen Johan A. P. Hiel Corry M. R. Weemaes F. J. M. Gabreëls Baziel G. M. van Engelen Dominique F. C. M. Smeets L. P. W. J. van den Heuvel 《Human genetics》1998,102(2):187-191
Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasia, immunodeficiency,
elevated α-fetoprotein levels, chromosomal instability, predisposition to cancer, and radiation sensitivity. We report the
identification of a new, double missense mutation in the ataxia telangiectasia gene (ATM) of a Dutch family. This homozygous
mutation consists of two consecutive base substitutions in exon 55: a T→G transversion at position 7875 of the ATM cDNA and
a G→C transversion at position 7876. These transversions were confirmed by polymerase chain reaction/primer-induced restriction
analysis with CelII. The double base substitution results in an amino acid change of an aspartic acid to a glutamic acid at codon 2625 and
of an alanine to a proline at codon 2626 of the ATM protein. Both amino acids are conserved between the ATM protein and its
functional homolog, the Atm gene product in the mouse. Furthermore, the Chou-Fasman and Robson predictions both demonstrate
a change in the secondary structure of the ATM protein carrying the D2625E/A2626P mutation. These findings suggest that the
double base substitution in the ATM gene is a disease-causing mutation.
Received: 6 October 1997 / Accepted: 5 November 1997 相似文献
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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
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Background
Seven donkey breeds are recognized by the French studbook and are characterized by a black, bay or grey coat colour including light cream-to-white points (LP). Occasionally, Normand bay donkeys give birth to dark foals that lack LP and display the no light points (NLP) pattern. This pattern is more frequent and officially recognized in American miniature donkeys. The LP (or pangare) phenotype resembles that of the light bellied agouti pattern in mouse, while the NLP pattern resembles that of the mammalian recessive black phenotype; both phenotypes are associated with the agouti signaling protein gene (ASIP).Findings
We used a panel of 127 donkeys to identify a recessive missense c.349 T > C variant in ASIP that was shown to be in complete association with the NLP phenotype. This variant results in a cysteine to arginine substitution at position 117 in the ASIP protein. This cysteine is highly-conserved among vertebrate ASIP proteins and was previously shown by mutagenesis experiments to lie within a functional site. Altogether, our results strongly support that the identified mutation is causative of the NLP phenotype.Conclusions
Thus, we propose to name the c.[349 T > C] allele in donkeys, the anlp allele, which enlarges the panel of coat colour alleles in donkeys and ASIP recessive loss-of-function alleles in animals.Electronic supplementary material
The online version of this article (doi:10.1186/s12711-015-0112-x) contains supplementary material, which is available to authorized users. 相似文献19.
Compound heterozygosity of a paternal submicroscopic deletion and a maternal missense mutation in POR gene: Antley‐bixler syndrome phenotype in three sibling fetuses 下载免费PDF全文
Anastasia Konstantinidou Konstantina Kosma Anastasios Mitrakos Christina Tzannatos Sofia Kitsiou‐Tzeli 《Birth defects research. Part A, Clinical and molecular teratology》2016,106(7):536-541