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1.
Choroideremia-locus maps between DXS3 and DXS11 on Xq 总被引:2,自引:0,他引:2
A. Gal F. Brunsmann D. Hogenkamp K. Rüther D. Ahlert T. F. Wienker W. Hammerstein I. H. Pawlowitzki 《Human genetics》1986,73(2):123-126
Summary Choroideremia is a progressive tapetochoroidal dystrophy with X-linked transmission leading frequently to blindness in affected males. The choroideremia-locus (TCD) has recently been assigned to the long arm of the X chromosome by linkage to polymorphic DNA markers. In order to further define the location of the gene defect, two families segregating for choroideremia were examined for DNA restriction fragment length polymorphisms. A search was undertaken for linkage with cloned DNA probes from the proximal short and long arm as well as from the mid-portion of the long arm of the X chromosome. Our data suggest that the most plausible gene order on the Xq is: Xcen-DXYS1-DXS3-TCD-DXS11-Xqter. 相似文献
2.
Zhang W Amir R Stockton DW Van Den Veyver IB Bacino CA Zoghbi HY 《American journal of human genetics》2000,66(4):1461-1464
We have identified a four-generation family with 10 affected females manifesting one or more of the following features: osseous dysplasia involving the metacarpals, metatarsals, and phalanges leading to brachydactyly, camptodactyly, and other digital deformities; pigmentary defects on the face and scalp; and multiple frenula. There were no affected males. We performed X-inactivation studies on seven affected females, using a methylation assay at the androgen receptor locus; all seven demonstrated preferential inactivation of their maternal chromosomes carrying the mutation, and two unaffected females showed a random pattern. These findings indicate that this disorder is linked to the X chromosome. To map the gene for this disorder, we analyzed DNA from nine affected females and five unaffected individuals, using 40 polymorphic markers evenly distributed throughout the X chromosome. Two-point and multipoint linkage analyses using informative markers excluded most of the X chromosome and demonstrated linkage to a region on the long arm between DXS548 and Xqter. A maximum LOD score of 3.16 at recombination fraction 0 was obtained for five markers mapping to Xq27.3-Xq28. The mapping data should facilitate the identification of the molecular basis of this disorder. 相似文献
3.
Andrew R. J. Curtis Sophie Headland Susan Lindsay Nicholas S. T. Thomas Eileen Boye Smaragda Kamakari Paul Roustan Maria Anvret Jan Wahlstrom Gillian McCarthy Angus J. Clarke Shomi Bhattacharya 《Human genetics》1993,90(5):551-555
Four families, each with two individuals affectecd by Rett Syndrome (RS), were analysed using restriction fragment lenght polymorphisms and microsatellite markers from the X chromosome. In two of the families, X-linked dominant inheritance of the RS defect from a germinally mosaic mother could be assumed. Therefore, maternal X chromosome markers showing discordant inheritance were used to exclude regions of the X chromosome as locations of the RS gene. Much of the short arm could be excluded, including regions containing three candidate genes, OTC, synapsin 1 and synaptophysin. Although most of the long arm was inherited in common it was possible to exclude a centromeric region. Inheritance of X chromosome markers is also presented for two families with affected aunt-niece pairs, one of which has not been previously studied at the DNA level. 相似文献
4.
Localisation of the Becker muscular dystrophy gene on the short arm of the X chromosome by linkage to cloned DNA sequences 总被引:13,自引:0,他引:13
Summary A linkage study in 30 Becker muscular dystrophy (BMD) kindreds using three cloned DNA sequences from the X chromosome which demonstrate restriction fragment length polymorphisms (RFLPs), suggests that the BMD gene is located on the short arm of the X chromosome, in the p21 region. The genes for Becker and Duchenne dystrophies must therefore be closely linked, if not allelic, and any future DNA probes found to be of practical use in one disorder should be equally applicable to the other. The linkage analysis also provides data on the frequency of recombination along the short arm of the X chromosome, and across the centromeric region. 相似文献
5.
M. Sarfarazi P. S. Harper H. M. Kingston J. M. Murray T. O'Brien K. E. Davies R. Williamson P. Tippett R. Sanger 《Human genetics》1983,65(2):169-171
The existence of linkage has been investigated between the Xg blood group system, two DNA restriction fragment length polymorphisms (RFLPs) located on the short arm of the X chromosome, Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). No linkage was found between the Xg locus and the more proximal RFLP (L 1.28); close linkage between Xg and the more distal RFLP (lambda RC8) was also excluded. Both RFLPs show linkage with DMD but are not closely linked with each other. Analyses of 11 families with DMD and ten with BMD, informative for the Xg blood group, reinforce the conclusions of others that there is no measurable linkage between the loci for Xg and for the X-linked forms of muscular dystrophy. 相似文献
6.
S. Fadda M. Mochi L. Roncuzzi S. Sangiorgi D. Sbarra M. Zatz G. Romeo 《Human genetics》1985,71(1):33-36
Summary A study of linkage between Becker muscular dystrophy and four X chromosome-specific DNA polymorphisms in 17 kindreds has indicated that this gene is located in Xp, as already anticipated by single pedigree analysis. In particular the DXS43 and DXS9 loci, identified by probes D2 and RC8, respectively, are closely linked to each other and are both located at approximately 15 cM from the Becker locus. These linkage data, together with the previously established linkage between Becker and the DXS7 locus identified by probe L 1.28, indicate that the Becker gene is located in the same region where Duchenne has been mapped and also yield information about relative genetic distances among different DNA polymorphisms of the X chromosome. 相似文献
7.
Trisomy 21 (Down syndrome): studying nondisjunction and meiotic recombination by using cytogenetic and molecular polymorphisms that span chromosome 21. 总被引:10,自引:6,他引:4
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G D Stewart T J Hassold A Berg P Watkins R Tanzi D M Kurnit 《American journal of human genetics》1988,42(2):227-236
By combining molecular and cytogenetic techniques, we demonstrated the feasibility and desirability of a comprehensive approach to analysis of nondisjunction for chromosome 21. We analyzed the parental origin and stage of meiotic errors resulting in trisomy 21 in each of five families by successfully using cytogenetic heteromorphisms and DNA polymorphisms. The 16 DNA fragments used to detect polymorphisms spanned the length of the long arm and detected recombinational events on nondisjoined chromosomes in both maternal meiosis I and maternal meiosis II errors. The meiotic stage at which errors occurred was determined by sandwiching the centromere between cytogenetic heteromorphisms on 21p and an informative haplotype constructed using two polymorphic DNA probes that map to 21q just below the centromere. This study illustrates the necessity of combining cytogenetic polymorphisms on 21p with DNA polymorphisms spanning 21q to determine (1) the source and stage of meiotic errors that lead to trisomy 21 and (2) whether an association exists between nondisjunction and meiotic recombination. 相似文献
8.
X-linked cleft palate: the gene is localized between polymorphic DNA markers DXYS12 and DXS17 总被引:2,自引:1,他引:1
A. Ivens G. E. Moore J. Chambers A. Arnason O. Jensson A. Bjornsson R. Williamson 《Human genetics》1988,78(4):356-358
Summary The gene involved in an X-linked form of cleft palate has been finely mapped using 14 restriction fragment length polymorphic (RFLP) markers that cover the long arm of the X chromosome. By the combination of deletion mapping and linkage analysis, the gene has been localized between the anonymous DNA markers DXYS12 on the proximal side, and DXS17 distally. 相似文献
9.
Genetic mapping of new DNA probes at Xq27 defines a strategy for DNA studies in the fragile X syndrome
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G. K. Suthers J. C. Mulley M. A. Voelckel N. Dahl M. L. Visnen P. Steinbach I. A. Glass C. E. Schwartz B. A. van Oost S. N. Thibodeau N. E. Haites B. A. Oostra R. Gin M. Carballo C. P. Morris J. J. Hopwood G. R. Sutherland 《American journal of human genetics》1991,48(3):460-467
The fragile X syndrome is the most common cause of familial mental retardation and is characterized by a fragile site at the end of the long arm of the X chromosome. The unusual genetics and cytogenetics of this X-linked condition make genetic counseling difficult. DNA studies were of limited value in genetic counseling, because the nearest polymorphic DNA loci had recombination fractions of 12% or more with the fragile X mutation, FRAXA. Five polymorphic loci have recently been described in this region of the X chromosome. The positions of these loci in relation to FRAXA were defined in a genetic linkage study of 112 affected families. The five loci--DXS369, DXS297, DXS296, IDS, and DXS304--had recombination fractions of 4% or less with FRAXA. The closest locus, DXS296, was distal to FRAXA and had a recombination fraction of 2%. The polymorphisms at these loci can be detected in DNA enzymatically digested with a limited number of restriction endonucleases. A strategy for DNA studies which is based on three restriction endonucleases and on five probes will detect one or more of these polymorphisms in 94% of women. This strategy greatly increases the utility of DNA studies in providing genetic advice to families with the fragile X syndrome. 相似文献
10.
Methods for the PCR amplification of five polymorphic sites in the region Xq21.33 to Xq24 were developed and used to predict heterozygosity for Fabry disease in informative families. Clones containing polymorphic sites associated with DNA segments DXS17, DXS87, and DXS287, and the alpha-galactosidase A gene were isolated from genomic libraries. Surrounding nucleotide sequences and optimal conditions for amplification of each polymorphic site were determined. These amplifiable polymorphisms provided predictions of heterozygosity for Fabry disease and should be useful for diagnostic linkage analyses in Alport syndrome, X-linked cleft palate and ankyloglossia, Pelizaeus-Merzbacher disease, and X-linked agammaglobulinemia as well as sequence-tagged sites for gene mapping. 相似文献
11.
Identification of novel RFLPs in the vicinity of CpG islands in Xq28: application to the analysis of the pattern of X chromosome inactivation.
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E Maestrini S Rivella C Tribioli M Rocchi G Camerino S Santachiara-Benerecetti O Parolini L D Notarangelo D Toniolo 《American journal of human genetics》1992,50(1):156-163
Probes for CpG islands were cloned from the distal long arm of the human X chromosome; three of them were found to be polymorphic. A HindIII RFLP was identified by the probe 2-25 (DXS606), and it was mapped to the Xq27-Xq28 boundary. Probes 2-19 (DXS605) and 2-55 (DXS707), which identify EcoRI and MspI polymorphisms, respectively, have been mapped to the distal part of Xq28, in the G6PD-RCP/GCP gene region. Probe 2-19 has been further localized about 16 kb from the 3' end of the G6PD gene. The new RFLPs may be useful for the precise mapping of the many disease genes localized in this part of the human X chromosome. Probe 2-19 is highly informative, and it has been studied in greater detail. Using the methylation-sensitive rare-cutter enzyme EagI in conjunction with the polymorphic EcoRI site, we were able to demonstrate that the RFLP may be used both to study randomness of X chromosome inactivation and for carrier detection in X-linked syndromes where nonrandom X inactivation occurs. It is conceivable that the combined use of 2-19 and of the probes described so far (pSPT-PGK and M27 beta) will make analysis of X inactivation feasible in virtually every female. 相似文献
12.
The parental origin of X chromosomes in XX males determined using restriction fragment length polymorphisms. 总被引:10,自引:10,他引:0
The inheritance of several X-linked restriction fragment length polymorphisms ( RFLPs ) is examined in seven 46,XX males and their immediate relatives. The XX males are shown to have inherited a paternal and a maternal RFLP allele in each of the five (of seven) families in which these X-linked markers are informative. In the other two families, a maternal X-chromosomal contribution is demonstrated, but a paternal contribution cannot be determined. We conclude that most, if not all, XX males inherit one paternal and one maternal X chromosome. A segment of single-copy DNA specific to the short arm of the Y chromosome is found to be absent from the genomes of eight XX males. In one of these XX males, an Xp-Yp translocation had previously been inferred from chromosome-banding studies. Our findings argue against mosaicism involving a Y-containing cell line in the XX males examined here, but they do not exclude an X-Y (or Y-autosome) translocation during paternal meiosis. If such a translocation has occurred, the translocation product received by the XX males does not include the Yp-specific sequence tested here. 相似文献
13.
Examination of X chromosome markers in Rett syndrome: exclusion mapping with a novel variation on multilocus linkage analysis.
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K A Ellison C P Fill J Terwilliger L J DeGennaro A Martin-Gallardo M Anvret A K Percy J Ott H Zoghbi 《American journal of human genetics》1992,50(2):278-287
Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and stereotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Maternal and paternal X chromosomes from the affected sisters were separated in somatic cell hybrids and were examined for concordance/discordance of maternal alleles at the tested loci. Thirty-six markers were informative in at least one of the two families, and 25 markers were informative in both families. Twenty loci were excluded as candidates for the Rett syndrome gene, on the basis of discordance for maternal alleles in the half-sisters. Nineteen of the loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than -2, we were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed. This in turn will result in a defined region of the X chromosome that should be searched for candidate sequences for the Rett syndrome gene in both familial and sporadic cases. 相似文献
14.
Wolfgang Berger Gerard van Duijnhoven Alfred Pinckers Arie Smits Hans-Hilger Ropers Frans Cremers 《Human genetics》1995,95(1):67-70
Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i. e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of >3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found. 相似文献
15.
A. Ballabio G. Parenti P. Tippett C. Mondello S. Di Maio A. Tenore G. Andria 《Human genetics》1986,72(3):237-240
Summary We report a large Italian pedigree in which five out of six males are affected by a syndrome, following an X-linked inheritance pattern, characterized by ichthyosis, hypogonadotropic hypogonadism, and anosmia. The concurrence of features of X-linked ichthyosis (XLI) with those of Kallmann syndrome, another disease often inherited as an X-linked trait, prompted us to perform biochemical, cytogenetic, and molecular studies in relation to the short arm of the X chromosome (Xp). Steroid sulphatase (STS) activity was found to be completely deficient in all affected members of the family. Prometaphase chromosome analyses of two obligate heterozygous women and one affected male showed normal karyotypes. Xg blood group antigen analysis and molecular studies employing cloned DNA sequences from the distal segment of the Xp (probes RC8, 782, dic56, and M1A), did not provide evidence for deletions or rearrangements of the X chromosome. The linkage analysis showed no crossovers between the disease, Xg, and DXS 143, the locus defined by probe dic56, thus suggesting the possibility of a linkage between these two markers of the distal segment of Xp and the X-linked ichthyosis, hypogonadism, and anosmia syndrome. 相似文献
16.
Choroideremia is linked to the restriction fragment length polymorphism DXYS1 at XQ13-21. 总被引:12,自引:3,他引:9
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Choroideremia (McK30310), an X-linked hereditary retinal dystrophy, causes night-blindness, progressive peripheral visual field loss, and, ultimately, central blindness in affected males. The location of choroideremia on the X chromosome is unknown. We have used restriction fragment length polymorphisms from the X chromosome to determine the regional localization of choroideremia by linkage analysis in families with this disease. One such polymorphic locus, DXYS1, located on the long arm (Xq) within bands q13-q21, shows no recombination with choroideremia at lod = 5.78. Therefore, with 90% probability, choroideremia maps within 9 centiMorgans (cM) of DXYS1. Another polymorphic locus, DXS11, located within Xq24-q26, also shows no recombination with choroideremia, although at a smaller lod score of 1.54 (90% probability limit theta less than 30 cM). This linkage with DXS11, a marker that is distal to DXYS1, suggests that the locus for choroideremia is also distal to DXYS1 and lies between these two markers in the region Xq13-q24. These results provide regional mapping for the disease that may be useful for prenatal diagnosis and, perhaps ultimately, for isolating the gene locus for choroideremia. 相似文献
17.
Mapping of locus for X-linked congenital stationary night blindness (CSNB1) proximal to DXS7. 总被引:4,自引:0,他引:4
A recombinant chromosome in a male affected with X-linked congenital stationary night blindness (CSNB1) provides new information on the location of the CSNB1 locus. A four-generation family with five males affected with X-linked CSNB was analyzed with five polymorphic markers for four X-chromosome loci spanning the region OTC (Xp21.1) to DXS255 (Xp11.22). Four of the males inherited the same X chromosome; one male inherited a chromosome that from OTC to DXS7, inclusive, was derived from the normal X chromosome of his unaffected grandfather and that from a location between DXS7 and DXS426 proximally was derived from the chromosome carrying the CSNB1 locus. This recombinant maps the CSNB1 locus in this family to a region on the short arm of the X chromosome proximal to the DXS7 locus. 相似文献
18.
D. Zhu D. M. Alcorn S. E. Antonarakis L. S. Levin P. C. Huang T. N. Mitchell A. C. Warren I. H. Maumenee 《Human genetics》1990,86(1):54-58
Summary There are three types of X-linked cataracts recorded in Mendelian Inheritance in Man (McKusick 1988): congenital total, with posterior sutural opacities in heterozygotes: congenital, with microcornea or slight microphthalmia; and the cataract-dental syndrome or Nance-Horan (NH) syndrome. To identify a DNA marker close to the gene responsible for the NH syndrome, linkage analysis on 36 members in a three-generation pedigree including seven affected males and nine carrier females was performed using 31 DNA markers. A LOD score of 1.662 at 0=0.16 was obtained with probe 782 from locus DXS85 on Xp22.2–p22.3. Negative LOD scores were found at six loci on the short arm, one distal to DXS85, five proximal, and six probes spanning the long arm were highly negative. These results make the assignment of the locus for NH to the distal end of the short arm of the X chromosome likely. 相似文献
19.
A highly polymorphic dinucleotide repeat on the proximal short arm of the human X chromosome: linkage mapping of the synapsin I/A-raf-1 genes. 总被引:4,自引:3,他引:1
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C U Kirchgessner J A Trofatter M M Mahtani H F Willard L J DeGennaro 《American journal of human genetics》1991,49(1):184-191
A compound (AC)n repeat located 1,000 bp downstream from the human synapsin I gene and within the last intron of the A-raf-1 gene has been identified. DNA data-base comparisons of the sequences surrounding the repeat indicate that the synapsin I gene and the A-raf-1 gene lie immediately adjacent to each other, in opposite orientation. PCR amplification of this synapsin I/A-raf-1 associated repeat by using total genomic DNA from members of the 40 reference pedigree families of the Centre d'Etude du Polymorphisme Humaine showed it to be highly polymorphic, with a PIC value of .84 and a minimum of eight alleles. Because the synapsin I gene has been mapped previously to the short arm of the human X chromosome at Xp11.2, linkage analysis was performed with markers on the proximal short arm of the X chromosome. The most likely gene order is DXS7SYN/ARAF1TIMPDXS255DXS146, with a relative probability of 5 x 10(8) as compared with the next most likely order. This highly informative repeat should serve as a valuable marker for disease loci mapped to the Xp11 region. 相似文献
20.
Mapping of the Emery-Dreifuss gene through reconstruction of crossover points in two Italian pedigrees 总被引:3,自引:0,他引:3
Giovanni Romeo Laura Roncuzzi Simonetta Sangiorgi Manlio Giacanelli Michele Liguori Daniela Tessarolo Mariano Rocchi 《Human genetics》1988,80(1):59-62
Summary Two unrelated pedigrees, which show recurrence of Emery-Dreifuss muscular dystrophy (EDMD) in three generations, have been studied using 13 X-linked DNA polymorphisms and somatic cell hybrids to establish the phase of the corresponding alleles in some obligate carriers. The reconstruction of cross-over points on the X chromosomes carrying the EDMD gene excludes from mapping most regions of the X chromosome except for the terminal portion of Xq. Pooled linkage data from the two pedigrees confirm the linkage previously reported with locus DXS15. A cross-over in a carrier female suggests that the EDMD gene is probably located distally to DXS15. In addition the recombinant meioses from one of the two pedigrees suggest the following order for some Xq polymorphic loci: DXS1 (DXYS1-DXS178) DXS42 (F9-DXS15). 相似文献