共查询到20条相似文献,搜索用时 997 毫秒
1.
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
2.
J. Deckert Markus M. Nöthen Stephan P. Bryant Simone Schuffenhauer Peter R. Schofield Nigel K. Spurr Peter Propping 《Human genetics》1997,99(3):326-328
Chromosome 22 contains two potential schizophrenia loci on chromosomal regions 22q11.2 and 22q12–13. In the present study
we report results from linkage mapping of the gene coding for the human A2a adenosine receptor (AR), which is one of two receptors mediating central nervous system effects of adenosine. From seven
CEPH (Centre d’Etude du Polymorphisme Humain) families, 120 individuals were typed utilizing an intragenic restriction fragment
length polymorphism. Significant linkage was found with many markers on chromosome 22. A 10-cM 1000 :1 support interval between
markers D22S301 and D22S300 is defined on the CHLC (Cooperative Human Linkage Center) framework map of chromosome 22. Localization
of the A2aAR gene outside the CATCH 22 syndrome region on 22q11.2 is demonstrated by the observation of heterozygous individuals with
defined 2-Mb deletions from this region. Thus, the A2aAR gene is not the schizophrenia susceptibility gene suspected in the CATCH 22 syndrome region on 22q11.2, but remains a candidate
for a schizophrenia susceptibility gene on 22q12–13.
Received: 10 August 1996 相似文献
3.
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
4.
Hong Wei Ma Elisabeth Lajeunie Nathalie de Parseval Arnold Munnich Dominique Renier Martine Le Merrer 《Human genetics》1996,98(2):228-232
Saethre-Chotzen syndrome is an autosomal dominant acrocephalosyndactyly syndrome whose gene has been assigned to chromosome
7p. Cytogenetic and linkage analyses have enabled the interval encompassing the disease gene to be delimited to a short region
of chromosome 7p15.3–p21.2. Based on the genetic analysis of three unreported families, we confirm the location of the disease
gene(s) in the interval defined by loci D7S664 and D7S493 (Zmax = 4.78 at * = 0 at the D7S488 locus) but fail to decide whether one or more disease-causing genes map in this genetic interval.
Received: 2 January 1996 / Revised: 21 March 1996 相似文献
5.
The Dombrock blood group system (DO) is a common polymorphism in Caucasians, represented by two red cell antigen alleles. In a linkage study in our family material
of 832 families from the Copenhagen area, we found a strong indication of tight linkage with the two flanking DNA polymorphisms
D12S358 (z = 7.66; at θ
M = 0.001, θ
F = 0.031) and D12S364 (z = 8.53; at θ
M = 0.068, θ
F = 0.031). DO is assigned to the region 12p13.2– 12p12.1 by physically localised markers.
Received: 18 April 1996 / Revised: 4 July 1996 相似文献
6.
Exon trapping was used to identify fragments of genes on human chromosome 21. One trapped sequence, hmc18h10 (GenBank no.
X88329), showed homology to a sequence (GenBank no. S65225) that includes the first three codons of the rat PEP-19 gene and
5′ untranslated leader region. We have cloned the corresponding cDNA for a human homolog of the rat PEP-19 gene and mapped
it to the region between markers ERG and D21S56 of chromosome 21q22.2–q22.3. Rat PEP-19 is a neuron-specific polypeptide expressed
in several regions of the central nervous system. It serves as a cell-specific marker in Purkinje cells and its expression
is developmentally regulated in the cerebellum, but its precise function is unknown. It is also presently unknown whether
overexpression of the PEP-19 gene is involved in certain phenotypes of Down syndrome.
Received: 3 May 1996 / Revised: 2 July 1996 相似文献
7.
Kazuhiro Kobayashi Yutaka Nakahori Kunihiko Mizuno Masashi Miyake Toshiyuki Kumagai Akira Honma Ikuya Nonaka Yusuke Nakamura Katsushi Tokunaga T. Toda 《Human genetics》1998,103(3):323-327
Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive, severe muscular dystrophy associated with brain
anomalies. After our initial mapping of the FCMD locus to 9q31–33, we performed linkage disequilibrium analysis, which led
us to suspect that the FCMD gene lay within a region of less than 100 kb containing D9S2107. In the present study, we developed
two new microsatellites (D9S2170 and D9S2171) in close vicinity to D9S2107 and examined haplotypes of FCMD chromosomes by
using four markers (cen-D9S2105-D9S2170-D9S2171-D9S2107-tel). As 82% of the FCMD chromosomes that we examined shared the founder
haplotype (138–192–147–183) and 94% of the FCMD patients in our panel carried founder haplotypes on one or both chromosomes,
the data supported the hypothesis of a single founder of this disease in the Japanese population. Eight haplotypes different
from the founder’s were observed in FCMD chromosomes, indicating that eight different FCMD mutations in addition to the founder’s
have occurred in Japan. Moreover, we have detected several historical recombinations that have disrupted the founder haplotype
at D9S2105 or D9S2170 and conclude that the FCMD gene is probably located just centromeric to D9S2170.
Received: 16 May 1998 / Accepted: 10 June 1998 相似文献
8.
L. Krols Jean-Jacques Martin Gilles David Nicole Van Regemorter Ali Benomar A. Löfgren Giovanni Stevanin Alexandra Dürr Alexis Brice C. Van Broeckhoven 《Human genetics》1997,99(2):225-232
We have previously mapped the gene for autosomal dominant cerebellar ataxia type II (ADCAII) to chromosome 3p12-p21.1 in
a region of 33 cM by using four families of different geographic origin. In this study, we analysed the families with nine
additional simple tandem repeat markers located in the ADCAII candidate region. An extensive clinical evaluation was also
performed in the Belgian family CA-1 on two probably affected and seven at-risk individuals by means of ophthalmological examination
and magnetic resonance imaging. Based on informative recombinants, we were able to reduce the ADCAII candidate region to the
12-cM region between D3S1300 and D3S1285. Furthermore, haplotype analysis among the families suggested that the most likely
location of the ADCAII gene is within the 6.2-cM interval between D3S3698 and D3S1285. Because of the documented anticipation
in ADCAII families, we also analysed family CA-1 with six polymorphic triplet repeat markers located on chromosome 3. None
of these markers showed expanded alleles.
Received: 16 August 1996 / Revised: 7 October 1996 相似文献
9.
10.
C. C. Shoulders Tamsin T. Grantham Julia D. North Achille Gaspardone Fabrizo Tomai Anna de Fazio Francesco Versaci Pier A. Gioffre Nancy J. Cox 《Human genetics》1996,98(5):557-566
Hypertriglyceridemia is a common metabolic disorder with a major inherited component. In some individuals the condition is
suspected to occur as a result of overproduction of apolipoprotein (apo)CIII, a major constituent of triglyceride-rich lipoproteins.
Population studies have established an association with the apoCIII gene but the identity of the causal mutation remains unknown.
In the present study we have examined a series of six 5′ polymorphic nucleotides (G–935 to A, C–641 to A, G–630 to A, deletion of T–625, C–482 to T, and T–455 to C) that lie within the promoter region of the apoCIII gene for evidence of possible involvement in disease susceptibility.
The polymorphic nucleotides at positions –455 and –482 reside within a negative insulin-response element. We show, in a community-based
sample of 503 school children, that a DNA polymorphism (S2 allele) within the 3′-noncoding region of the apoCIII gene was
associated with elevated apoCIII and triglyceride levels, but that the polymorphic nucleotides of the promoter were not. In
addition, no obvious effect of any extended apoCIII promoter haplotype on plasma apoCIII or triglyceride levels, over and
above that conferred by the presence of the S2 polymorphic nucleotide, was detected. These results demonstrate that none of
the 5′ apoCIII polymorphisms can account for the association of the apoCIII gene locus with hypertriglyceridemia and, moreover,
owing to linkage disequilibrium, raise the possibility that the region conferring susceptibility maps downstream, rather than
upstream, of the apoCIII gene promoter sequences.
Received: 8 January 1996 / Revised: 30 May 1996 相似文献
11.
Isolated autosomal dominant hypoparathyroidism is a heterogeneous disorder characterized by parathyroid hormone (PTH) deficiency,
hypocalcemia and hyperphosphatemia. The candidate gene approach was used to study a large Norwegian family. The loci for the
PTH gene, PTH receptor gene and RET protooncogene were excluded using dinucleotide markers and restriction fragment length
polymorphism analysis. Complete cosegregation of this trait was found with the chromosomal region 3q13, using the short tandem
repeat markers D3S1267, D3S1269, D3S1303, D3S1518, and RHO. This region contains the candidate locus for the Ca2+-sensing receptor (PCAR1). By single-strand conformation polymorphism (SSCP) analysis of all PCAR1 exons followed by automated
sequencing, we identified a C to T transition in exon 2 (cDNA position 452) on the mutant allele in the family. The mutation
predicts a substitution of Thr to Met in amino acid position 151 (T151M). A StyI restriction site created by the nucleotide substitution was used to confirm the mutation on all alleles, as well as to exclude
it among 100 normal alleles (blood donors). SSCP analysis also identified a novel polymorphism of PCAR1 intron 4 (1609–88t→c)
on normal alleles.The T151M mutation is located in the extracellular N-terminal domain of PCAR1, which belongs to the superfamily
of G protein-coupled receptors. We suggest that this is a gain-of-function mutation that increases the sensitivity of the
receptor to [Ca2+], thereby decreasing the calcium set point.
Received: 29 September 1995 / Revised: 19 January 1996 相似文献
12.
B. Edman Ahlbom Muhammad Yaqoob Agne Larsson Adam Ilicki Göran Annerén C. Wadelius 《Human genetics》1997,99(2):186-190
Congenital hypothyroidism affects 1/3000– 4000 newborns. The causes of this group of disorders are still largely unknown.
Although most cases are sporadic, some families have several affected children and/or consanguineous parents, suggesting autosomal
recessive inheritance. Furthermore, there is a murine strain (hyt) with congenital hypothyroidism and autosomal recessive
inheritance, whose phenotype appears to be identical with the corresponding human disease. In the hyt mouse, the disease is
caused by a mutation in the thyroid-stimulating hormone receptor (TSHR) gene, making this gene a likely candidate also for
the human disease. The human TSHR gene was mapped on radiation hybrid panels and closely linked flanking markers D14S287 and
D14S616 were identified. On the Genebridge 4 panel, D14S287 was found to be located 8.5 cR (corresponding to 2.3 cM) proximal
to the TSHR gene, and D14S616 was found to be located 4.4 cR (1.2 cM) distal to the TSHR gene. These markers were analyzed
in 23 families, most of them with two or more children affected by congenital hypothyroidism and some with appreciable consanguinity
of the parents. Assuming homogeneity, the two-point lod score at θ = 0.1 was –4.8 for D14S287 and –5.8 for D14S616, and thus
linkage to the TSHR gene was excluded. Even when the data were analyzed with allowance for heterogeneity, there was no evidence
of linkage. Our conclusion is that if mutation of the TSHR gene causes familial congenital hypothyroidism in humans, it affects
only a small proportion of the cases.
Received: 8 July 1996 相似文献
13.
Alopecia with mental retardation syndrome is a rare autosomal recessive disorder characterized clinically by total or partial
alopecia and mental retardation. In an effort to understand the molecular bases of this form of alopecia syndrome, large Pakistani
consanguineous kindred with multiple affected individuals has been ascertained from a remote region in Pakistan. Genome wide
scan mapped the disease locus on chromosome 3q26.33–q27.3. A maximum two-point LOD score of 3.05 (θ=0.0) was obtained at marker
D3S3583. Maximum multipoint LOD score exceeding 5.0, obtained with several markers, supported the linkage. Recombination events
observed in affected individuals localized the disease locus between markers D3S1232 and D3S2436, spanning 11.49-cM region
on chromosome 3q26.33–q27.3. Sequence analysis of a candidate gene ETS variant gene 5 from DNA samples of two affected individuals
of the family revealed no mutation. 相似文献
14.
Anne Meyer Alain Béchetoille Françoise Valtot Stéphane Dupont de Dinechin Marie F. Adam Ahmed Belmouden Antoine P. Brézin Lucienne Gomez Jean-François Bach H.-J. Garchon 《Human genetics》1996,98(5):567-571
The GLC1A locus for autosomal dominant primary open-angle glaucoma (POAG) with juvenile onset (before 20 years) has been
mapped to chromosome 1q21– q31. Recently, a French-Canadian family was described in which both juvenile-onset and middle-age
or early-onset POAG were observed and linked to GLC1A. We now describe a second POAG family with variable age of onset (range
11–51, median 36 years of age). Linkage to GLC1A was established with a maximum lod score of 6.21 at the D1S452 locus. A recombination
event in a severely glaucomatous patient restricted the distal boundary of the GLC1A interval proximal to the AFM154xc9 marker.
This study strengthens the idea that early-onset POAG may also be determined by the GLC1A genetic region.
Received: 6 May 1996 / Revised: 21 June 1996 相似文献
15.
16.
D. Markie Susan Huson Eddie Maher Angela Davies I. Tomlinson Walter F. Bodmer 《Human genetics》1996,98(2):125-128
Karyotypic analysis in a patient with Peutz-Jeghers’ syndrome demonstrated a pericentric inversion on chromosome 6. Further
investigation was undertaken using fluorescence in situ hybridisation (FISH) with yeast artificial chromosome clones selected
to contain genetic markers from chromosome 6, and a probe for the centromeric alphoid repeat array. This analysis located
one inversion breakpoint within the alphoid array, in a 1-cM interval between D6S257 and D6S402, and the other in a 4-cM interval
between D6S403 and D6S311. The oestrogen receptor gene locus (ESR) is excluded from the latter interval.
Received: 23 January 1996 / Revised: 26 February 1996 相似文献
17.
Hiroyuki Satoh Naomi Inokuchi Yasuhiro Nagae Taro Okazaki 《Journal of molecular evolution》1999,49(1):122-129
The β-globin gene cluster of Wistar rat was extensively cloned and the embryonic genes were mapped and sequenced. Four overlapping
λ Dash recombinant clones cover about 31 kb and contain four nonadult β-globin genes, 5′–ε1–γ1–γ2–ψγ3–3′. The ε1 and γ2 are
active genes, since their protein products were detected in the fetal stage of the rat (Iwahara et al., J Biochem 119:360–366,
1996). The γ1 locus might be a pseudogene, since the ATA box in the promoter region is mutated to GTA; however, no other defect
is observed. The ψγ3 locus is a truncated pseudogene because a 19-base deletion, which causes a shift of the reading frame,
is observed between the second nucleotide of the putative codon 68 and codon 76. A sequence comparison suggests that the ψγ3
might be produced by a gene conversion event of the proto-γ-globin gene set. Possible histories of the evolution of rat nonadult
β-globin genes are discussed.
Received: 6 August 1998 / Accepted: 12 February 1999 相似文献
18.
19.
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
20.
G. P. Patrinos Panagoula Kollia Aphrodite Loutradi-Anagnostou Dimitris Loukopoulos Manoussos N. Papadakis 《Human genetics》1998,102(6):629-634
We report a new type of non-deletional hereditary persistence of fetal hemoglobin that is due to a C→T transition at position
–158, relative to the Cap site of the human Aγ-globin gene. This mutation was identified in three unrelated adult cases presenting slightly elevated levels of fetal hemoglobin
(Hb F), i.e. 2.9–5.1%, and normal hematological indices. Our sequencing results, from both polymerase chain reaction-amplified
and subcloned DNA fragments, indicate that the Aγ–158C→T mutation occurred by two independent gene conversion events in the three cases studied. In addition, hematological
and molecular data, including restriction fragment length polymorphism haplotyping in the β-globin gene cluster, extended haplotype analysis inside the γ-globin gene region and routine analysis of three tandem repeat loci (D1S80, 3′-HVR/apoB and F8vWf), led us to conclude that
the Aγ–158C→T mutation in one of the three cases occurred recently in the parental germ line (P=99.47%), representing the first example of a de novo gene conversion event identified in humans.
Received: 10 November 1997 / Accepted: 10 February 1998 相似文献