共查询到20条相似文献,搜索用时 15 毫秒
1.
Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5 总被引:39,自引:10,他引:29
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yusuke Nakamura Mark Lathrop Mark Leppert Marc Dobbs John Wasmuth Erica Wolff Mary Carlson Esther Fujimoto Karen Krapcho Tena Sears Scott Woodward J. Hughes Randy Burt Eldon Gardner Jean-Marc Lalouel Ray White 《American journal of human genetics》1988,43(5):638-644
Familial adenomatous polyposis (FAP), a Mendelian disorder that includes familial polyposis coli (FPC) and Gardner syndrome (GS), has an autosomal dominant mode of inheritance. It is characterized by hundreds to thousands of adenomatous polyps that can progress to carcinoma of the colon, suggesting that the gene that harbors the FAP germ-line mutation may play an important role in the somatic genetic pathway to colon cancer. The defect responsible for FAP was recently mapped to the long arm of chromosome 5 by linkage between the FPC phenotype and a locus defined by DNA probe pC11p11 (D5S71), located at 5q21-22. Because an important next step in the paradigm for identification of a disease gene is to obtain a more precise localization, we isolated and mapped by linkage six additional polymorphic DNA markers in the FAP region. Subsequent linkage analysis in six pedigrees, three having the FPC phenotype and three segregating GS, placed the FAP locus very close to a new marker, YN5.48 (D5S81), that is approximately 17 centimorgans distal to C11p11 on the genetic map. The analysis revealed no evidence of genetic heterogeneity between the two phenotypes, a question that had not been clearly resolved by the earlier studies. The new set of markers in the near vicinity of the FAP locus represents a further step toward isolation of the genetic defect and provides the opportunity for preclinical diagnosis of risk status for colon cancer among individuals in families that are segregating adenomatous polyposis. 相似文献
2.
Alessandro Stella Nicoletta Resta Angela Polizzi Mariapina Montera Filomena Cariola Francesco Susca Viviana Gismondi Lucio Bertario Cristiana Marchese Romano Tenconi Maria Grazia Tibiletti Paola Izzo Mattia Gentile Fernando Prete Oronzo Pannarale Giovanni Di Matteo Paola Sala Liliana Varesco Cristina Mareni G. Guanti 《Human genetics》1998,102(6):624-628
In the present study, we used five different polymorphic markers to construct the haplotype at the adenomatous polyposis
coli (APC) locus in families with familial adenomatous polyposis (FAP) and in the normal Italian population. Non-ambiguous
haplotypes were reconstructed from 246 normal chromosomes and 65 FAP chromosomes. In the control population, the four polymorphisms
intragenic to APC gave rise to 16 haplotypes, the most common of which (II and XV) accounted for over 50% of all chromosomes.
In FAP patients, 13 haplotypes were found but their distribution was not statistically different from normal subjects. Eighty
complete chromosomal haplotypes (many fewer than the theoretical maximum of 208) for the five polymorphic sites assayed were
observed in the control population, 35 being found in the FAP patients. We compared the distribution of these haplotypes within
the two groups; no statistically significant differences between normal and FAP chromosomes were found. The elevated heterogeneity
of FAP chromosomes was clearly confirmed by the observation that 19 patients who carried one or other of the two most common
APC mutations (nt 3183 and nt 3927) showed 18 different haplotypes. On the basis of these results, we were not able to identify
a founder FAP chromosome. Various mechanisms are presented to explain this observation.
Received: 5 November 1997 / Accepted: 3 February 1998 相似文献
3.
Evidence for a novel glaucoma locus at chromosome 3p21-22 总被引:2,自引:0,他引:2
Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the world. It is a clinically variable group of diseases with the majority of cases presenting as the late onset adult type. Several chromosomal loci have been implicated in disease aetiology, but causal mutations have only been identified in a small proportion of glaucoma. We have previously described a large six-generation Tasmanian family with POAG exhibiting genetic heterogeneity. In this family, approximately one third of affected individuals presented with a glutamine-368-STOP (Q368STOP) mutation in the myocilin gene. We now use a Markov Chain Monte Carlo (MCMC) method to identify a second disease region in this family on the short arm of chromosome 3. This disease locus was initially mapped to the marker D3S1298 and a subsequent minimum disease region of 9 cM between markers D3S1298 and D3S1289 was identified through additional mapping. The region did not overlap with any previously described locus for POAG. Using a multiplicative relative risk model, we identified a positive association between this region and the Q368STOP mutation of myocilin on chromosome 1 in affected individuals. These findings provide evidence of a new autosomal dominant glaucoma locus on the short arm of chromosome 3. 相似文献
4.
P Raeymaekers P De Jonghe L Swerts G De Winter J Gheuens J J Martin A Vandenberghe C Van Broeckhoven 《Cytogenetics and cell genetics》1989,50(2-3):178-180
We previously described a large five-generation family with autosomal dominant inheritance of hereditary motor and sensory neuropathy type I, or Charcot-Marie-Tooth disease (CMT1). The genetic defect in this family was not linked to the Duffy blood group. We investigated the possibility of a disease locus on the short arm of chromosome 1 using 12 anonymous DNA markers. Two markers, D1S2 and D1S22, showed positive linkage, suggesting the existence of a CMT1 locus on 1p. D1S2 and D1S22 are clustered in the 1p31----p22 region. However, multipoint linkage analysis, including additional DNA markers from this chromosome region, excluded a possible CMT1 locus in this part of chromosome 1. 相似文献
5.
Hidewaki Nakagawa Kumiko Koyama Toshihiro Tanaka Yasuo Miyoshi Hiroshi Ando Shozo Baba Masahiro Watatani Masayuki Yasutomi Morito Monden Yusuke Nakamura 《Human genetics》1998,102(2):203-206
Patients with Peutz-Jeghers syndrome (PJS), an autosomal dominant disease characterized by hamartomatous polyposis of the
gastrointestinal tract, are thought to be predisposed to malignancies of the digestive tract, genital tract, and other organs.
Using microsatellite markers on chromosome 19p, we have closely defined the region containing the gene responsible for this
disorder through linkage analysis in seven affected families. The lack of obligate recombinants at two of these loci, D19S883
and D19S878, with maximum LOD scores of 2.88 and 3.75, confirmed the localization of the PJS locus to chromosome 19. Furthermore,
haplotype analysis placed the PJS locus within a 6-cM telomeric region of chromosome 19p, between D19S886 and D19S565.
Received: 18 August 1997 / Accepted: 5 November 1997 相似文献
6.
7.
Genetic linkage map of six polymorphic DNA markers around the gene for familial adenomatous polyposis on chromosome 5. 总被引:9,自引:2,他引:7
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M G Dunlop A H Wyllie Y Nakamura C M Steel H J Evans R L White C C Bird 《American journal of human genetics》1990,47(6):982-987
A genetic linkage map of six polymorphic DNA markers close to the gene (APC) for familial adenomatous polyposis (FAP) on chromosome 5q is reported. One hundred fifty-five typed members of nine FAP kindred provided more than 90 meioses for linkage analysis. A number of crucial recombination events have been identified which are informative at three or more loci, allowing confident ordering of parts of the map. There was no evidence of genetic heterogeneity, with all families showing linkage of at least one chromosome 5 marker to the gene. Recombination data and two-point linkage analysis support a locus order of centromere-pi 227-C11P11-ECB27-L5.62-APC-EF5.44-YN5.48-telomer e, although EF5.44 could lie in the interval L5.62-APC or ECB27-L5.62. No recombinants were identified between APC and either EF5.44 or YN5.48, but published deletion mapping in colorectal carcinomas and linkage analysis in FAP suggest that YN5.48 is 1-3 cM from APC. The present study suggests that YN5.48 and L5.62 delineate a small region of chromosome 5 within which the EF5.44 locus lies very close to the APC gene. These data not only allow use of flanking markers for presymptomatic diagnosis of FAP but also provide a high-density map of the region for isolation of the APC gene itself and for further assessment of the role of chromosome 5 deletions in the biology of sporadic colorectal cancer. 相似文献
8.
Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a cuban founder-effect population 总被引:8,自引:5,他引:3
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Georg Auburger Guillermo Orozco Diaz Raul Ferreira Capote Suzana Gispert Sanchez Marta Paradoa Perez Marianela Estrada del Cueto Mirna Garcia Meneses Martin Farrall Robert Williamson Susan Chamberlain Luis Heredero Baute 《American journal of human genetics》1990,46(6):1163-1177
The locus for autosomal dominant ataxia with a diagnosis of olivo-ponto-cerebellar atrophy at autopsy has been previously assigned to chromosome 6p. However, evidence for two alternative locations has been reported. We have recently described a large potential founder-effect population of such patients in the Holguin province of Cuba. With an estimated 1,000 patients available for analysis, this extensive cluster of families provides a unique opportunity for the definitive localization of the genetic mutation. Linkage analysis between the disease locus in this population and markers within and flanking the HLA region on chromosome 6 were undertaken in 12 families comprising over 100 affected individuals. Despite similarity in the clinical phenotype between those families where the disease locus has been reported to be linked to the HLA locus and the Cuban patients, no evidence of linkage to this region could be demonstrated in the latter. The disease locus was excluded from a 96-cM genetic interval of the short arm of chromosome 6, encompassing the F13A1-HLA-GLO1-MUT/D6S4 loci. These data strongly support the existence of genetic heterogeneity for the disease. 相似文献
9.
Yang X She C Guo J Yu AC Lu Y Shi X Feng G He L 《American journal of human genetics》2000,66(3):892-903
Brachydactyly type A-1 (BDA1) was, in 1903, the first recorded example of a human anomaly with Mendelian autosomal dominant inheritance. Two large families, the affected members of which were radiographed, were recruited in the study we describe here. Two-point linkage analysis for pedigree 1 (maximum LOD score [Zmax] 6.59 at recombination fraction [theta] 0.00) and for pedigree 2 (Zmax=5.53 at straight theta=0.00) mapped the locus for BDA1 in the two families to chromosome 2q. Haplotype analysis of pedigree 1 confined the locus for family 1 within an interval of <8.1 cM flanked by markers D2S2248 and D2S360, which was mapped to chromosome 2q35-q36 on the cytogenetic map. Haplotype analysis of pedigree 2 confined the locus for family 2 within an interval of <28. 8 cM flanked by markers GATA30E06 and D2S427, which was localized to chromosome 2q35-q37. The two families had no identical haplotype within the defined region, which suggests that the two families were not related. 相似文献
10.
Identification of a locus which shows no genetic recombination with the autosomal dominant polycystic kidney disease gene on chromosome 16. 总被引:19,自引:7,他引:12
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
G G Germino N J Barton J Lamb D R Higgs P Harris G H Xiao G Scherer Y Nakamura S T Reeders 《American journal of human genetics》1990,46(5):925-933
The major site for mutations leading to autosomal dominant polycystic kidney disease (ADPKD) is at the PKD1 locus, previously mapped to 16p13. Three additional probes have now been mapped within an existing array of genetic markers flanking this locus. One of these, CMM65b (D16S84), shows no recombination with PKD1 in 201 informative meioses. The others, Fr3-42 (D16S21) and EKMDA2 (D16S83), are shown to be the closest telomeric flanking markers. Somatic cell hybrids containing derivative chromosome 16s were used to construct a physical map of the region. Cosmid overlap cloning of the D16S84 region allowed a t(16;1) translocation breakpoint to be mapped at the molecular level, orientating the extended D16S84 locus with respect to the chromosome. The new markers and physical map described here provide an improved framework for attempts to clone the PKD1 region and to identify polycystic kidney disease mutations. 相似文献
11.
B. D. Gelb Eric Spencer Suliman Obad Gordon J. Edelson Simon Faure Jean Weissenbach Robert J. Desnick 《Human genetics》1996,98(2):141-144
Pycnodysostosis (PKND) is a rare, autosomal recessive skeletal dysplasia, which has been mapped previously to a 4-cM interval
between D1S442 to D1S305 at chromosome 1q21. Only D1S498 did not recombine with the disease locus in a large, consanguineous Arab family with PKND. In the present studies, five new
Généthon markers (D1S2343, D1S2344, D1S2345, D1S2346, and D1S2347) were tested against DNA from this family and against the Stanford G3 diploid radiation hybrid panel. The results permitted
ordering of some loci previously mapped at no recombinant distance: D1S442-D1S2344-(D1S498/ D1S2347)-(D1S2343/D1S2345)-D1S2346-D1S305. The PKND critical region was refined to the 2-cM interval from D1S2344 to D1S2343/D1S2347. In addition, sequence-tagged sites were developed for the two PKND candidate genes, IL6R and MCL1. Use of radiation hybrids
revealed that IL6R was tightly linked to D1S305, excluding it from the PKND critical region. MCL1 was most tightly linked to D1S498 and D1S2347, placing it within the critical region.
Received: 8 November 1995 / Revised: 12 February 1996 相似文献
12.
Autosomal dominant spastic paraplegia with anticipation maps to a 4-cM interval on chromosome 2p21-p24 in a large German family 总被引:8,自引:0,他引:8
Joachim Bürger Hermann Metzke Caroline Paternotte Frank Schilling Jamilé Hazan André Reis 《Human genetics》1996,98(3):371-375
Autosomal dominant familial spastic paraplegias (AD-FSP) are a group of genetically heterogeneous diseases characterised
by a progressive spasticity of the lower limbs. Three loci have already been identified by genetic linkage studies on chromosomes
2p, 14q and 15q. Here we present linkage data from a large German family displaying AD-FSP with anticipation which confirms
the existence of the FSP2 locus on chromosome 2p. The recombination events observed in our family define the critical region
for the FSP2 gene to be within a 4-cM interval, flanked by markers D2S400 and D2S367. Moreover, clinical data from our family
show evidence of anticipation, a phenomenon caused by trinucleotide expansion in several other neurodegenerative diseases.
Received: 6 April 1996 / Revised: 22 April 1996 相似文献
13.
Gul Naz Ghazanfar Ali Syed Kamran-ul-Hassan Naqvi Zahid Azeem Wasim Ahmad 《Human genetics》2010,127(4):395-401
Autosomal recessive hypotrichosis is a rare form of human genetic disorder characterized by sparse to absent hair on scalp
and rest of the body of affected individuals. Over the past few years at least five autosomal recessive forms of hypotrichosis
loci have been mapped on different human chromosomes. In the present study, we report localization of another novel autosomal
recessive hypotrichosis locus on human chromosome 10q11.23–22.3 in a four generation consanguineous Pakistani family. All
the four patients in the family showed typical features of hereditary hypotrichosis including sparse hair on the scalp and
rest of the body. Human genome scan using highly polymorphic microsatellite markers mapped the disease locus to a large region
on chromosome 10. This novel locus maps to 29.81 cM (28.5 Mb) region, flanked by markers D10S538 and D10S2327 on chromosome
10q11.23–22.3. A maximum multipoint LOD score of 3.26 was obtained with several markers in this region. DNA sequence analysis
of exons and splice-junction sites of four putative candidate genes (P4HA1, ZNF365, ZMYND17, MYST4), located in the linkage interval, were sequenced but were negative for functional sequence variants. 相似文献
14.
Synteny on mouse chromosome 5 of homologs for human DNA loci linked to the Huntington disease gene 总被引:4,自引:0,他引:4
S V Cheng G R Martin J H Nadeau J L Haines M Bucan C A Kozak M E MacDonald J L Lockyer F D Ledley S L Woo 《Genomics》1989,4(3):419-426
Comparative mapping in man and mouse has revealed frequent conservation of chromosomal segments, offering a potential approach to human disease genes via their murine homologs. Using DNA markers near the Huntington disease gene on the short arm of chromosome 4, we defined a conserved linkage group on mouse chromosome 5. Linkage analyses using recombinant inbred strains, a standard outcross, and an interspecific backcross were used to assign homologs for five human loci, D4S43, D4S62, QDPR, D4S76, and D4S80, to chromosome 5 and to determine their relationships with previously mapped markers for this autosome. The relative order of the conserved loci was preserved in a linkage group that spanned 13% recombination in the interspecific backcross analysis. The most proximal of the conserved markers on the mouse map, D4S43h, showed no recombination with Emv-1, an endogenous ecotropic virus, in 84 outcross progeny and 19 recombinant inbred strains. Hx, a dominant mutation that causes deformities in limb development, maps approximately 2 cM proximal to Emv-1. Since the human D4S43 locus is less than 1 cM proximal to HD near the telomere of chromosome 4, the murine counterpart of the HD gene might lie between Hx and Emv-1 or D4S43h. Cloning of the region between these markers could generate new probes for conserved human sequences in the vicinity of the HD gene or possibly candidates for the murine counterpart of this human disease locus. 相似文献
15.
S G Ryan M J Dixon M A Nigro K A Kelts O N Markand J C Terry R Shiang J J Wasmuth P O''''Connell 《American journal of human genetics》1992,51(6):1334-1343
Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. We performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region. 相似文献
16.
Localization of the gene for autosomal recessive congenital hereditary endothelial dystrophy (CHED2) to chromosome 20 by homozygosity mapping. 总被引:3,自引:0,他引:3
Congenital hereditary endothelial dystrophy (CHED) is a corneal disorder that presents with diffuse bilateral corneal clouding. Vision may be severely impaired, and many patients require corneal transplantation. Both autosomal dominant (AD) and autosomal recessive (AR) forms of the disorder have been described. The gene responsible for AD CHED (HGMW-approved symbol CHED1) has been mapped to the pericentromeric region of chromosome 20. Investigating a large, consanguineous Irish pedigree with autosomal recessive CHED, we have previously excluded linkage to this AD CHED locus. We now describe a genome-wide search using homozygosity mapping and DNA pooling. Evidence of linkage to chromosome 20p was demonstrated with a maximum lod score of 9.30 at a recombination fraction of 0.0 using microsatellite marker D20S482. A region of homozygosity in all affected individuals was identified, narrowing the disease gene locus to an 8-cM region flanked by markers D20S113 and D20S882. This AR CHED (HGMW-approved symbol CHED2) disease gene locus is physically and genetically distinct from the AD CHED locus. 相似文献
17.
Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21-22. 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
D Krakow K Reinker B Powell R Cantor M A Priore A Garber R S Lachman D L Rimoin D H Cohn 《American journal of human genetics》1998,63(1):120-124
Multiple synostoses syndrome is an autosomal dominant disorder characterized by premature onset of joint fusions, which initially affect the interphalangeal joints, by characteristic facies, and by deafness. We performed linkage analysis on a large Hawaiian family with multiple synostoses syndrome. Because another autosomal dominant disorder, proximal symphalangism, shares some clinical symptoms with multiple synostoses syndrome and has been linked to markers at loci at chromosome 17q21-22, we tested the hypothesis that multiple synostoses syndrome is linked to the same chromosomal region. Using polymorphic markers from the proximal symphalangism interval, we conducted linkage analysis and showed that the multiple synostoses-syndrome phenotype is linked to the same chromosomal region. A maximum LOD score of 3.98 at recombination fraction of .00 was achieved for the marker at locus D17S787. Further genetic analysis identified individuals with recombinant genotypes, allowing localization of the disease gene within the interval D17S931-D17S792, a 16-cM region. These data provide evidence that multiple synostoses syndrome and proximal symphalangism may be allelic disorders. 相似文献
18.
Theendakara V Tromp G Kuivaniemi H White PS Panchal S Cox J Winters RS Riebeling P Tost F Hoeltzenbein M Tervo TM Henn W Denniger E Krause M Koksal M Kargi S Ugurbas SH Latvala T Shearman AM Weiss JS 《Human genetics》2004,114(6):594-600
Schnyders crystalline corneal dystrophy (SCCD) is a rare autosomal dominant eye disease with a spectrum of clinical manifestations that may include bilateral corneal clouding, arcus lipoides, and anterior corneal crystalline cholesterol deposition. We have previously performed a genome-wide linkage analysis on two large Swede-Finn families and mapped the SCCD locus to a 16-cM interval between markers D1S2633 and D1S228 on chromosome 1p36. We have collected 11 additional families from Finland, Germany, Turkey, and USA to narrow the critical region for SCCD. Here, we have used haplotype analysis with densely spaced microsatellite markers in a total of 13 families to refine the candidate interval. A common disease haplotype was observed among the four Swede-Finn families indicating the presence of a founder effect. Recombination results from all 13 families refined the SCCD locus to 2.32 Mbp between markers D1S1160 and D1S1635. Within this interval, identity-by-state was present in all 13 families for two markers D1S244 and D1S3153, further refining the candidate region to 1.58 Mbp. 相似文献
19.
Wim Van Hul Hubert Backhovens Guy Van Camp Piet Stinissen Marc Cruts Anita Wehnert Christine Van Broeckhoven 《Human genetics》1991,87(2):109-111
Summary We were able to refine the chromosomal position of two existing marker loci, using an extended chromosome 21 somatic cell hybrid panel. The locus D21S26 mapped in the region 21q11.2–q21.1, and the locus D21S24 in 21q22.1–q22.2. Physical and genetic analysis indicated that D21S26 is tightly linked to D21S13 and D21S16, two markers previously linked to familial Alzheimer's disease. 相似文献
20.
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