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1.
Génin E Huebner A Jaillard C Faure A Halaby G Saka N Clark AJ Durand P Bégeot M Naville D 《Human genetics》2002,111(4-5):428-434
In several cases of familial glucocorticoid deficiency (FGD), referred to as FGD type 1, mutations have been described in the coding exon of the adrenocorticotropin receptor (melanonocortin receptor type 2, MC2R) gene. However, for the majority of cases (FGD type 2), no mutations were found in this gene. In the more informative families, the involvement of the MC2R locus could be excluded by linkage or sequencing analysis and, as there was no obvious candidate gene, a genome linkage scan was performed. Fourteen families were studied in this report. Evidence of linkage was found with markers on chromosome 8q in three out of the 14 families (maximum heterogeneity LOD score of 2.81 at D8S1763). These three families were consanguineous and the gene could be located by homozygosity mapping between markers D8S285 and D8S1718 in a 8.8-cM region. No potential candidate genes were apparent in the region. Linkage to this region could be excluded in some families from our sample giving highly negative LOD scores with the markers of the region. This result suggests that at least one other gene, located on a different region, must be responsible for FGD in these families and provides new evidence of genetic heterogeneity of this disorder. 相似文献
2.
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
3.
L Haddad I N Day S Hunt R R Williams S E Humphries P N Hopkins 《Journal of lipid research》1999,40(6):1113-1122
Monogenically inherited hypercholesterolemia is most commonly caused by mutations at the low density lipoprotein receptor (LDLR) locus causing familial hypercholesterolemia (FH) or at the apolipoprotein B (APOB) locus causing the disorder familial defective apoB (FDB). Probands from 47 kindreds with a strict clinical diagnosis of FH were selected from the Cardiovascular Genetics Research Lipid Clinic, Utah, for molecular genetic analysis. Using a combination of single-strand conformation polymorphism (SSCP) and direct sequencing, 12 different LDLR gene mutations were found in 16 of the probands. Three of the probands were carriers of the APOB R3500Q mutation. In five of the remaining 28 pedigrees where no mutation had been detected, samples from enough relatives were available to examine co-segregation with the LDLR region using the microsatellite marker D19S221, which is within 1 Mb centromeric of the LDLR locus, and D19S394, sited within 150 kb telomeric of the LDLR locus. In four of the families there was strong evidence for co-segregation between the LDLR locus and the phenotype of hypercholesterolemia, but in one large family with 18 living affected members and clear-cut bimodal hypercholesterolemia, there were numerous exclusions of co-segregation. Using length polymorphic markers within and outside the APOB gene, linkage of phenotype in this family to the APOB region was similarly excluded. In this large family, the degree of hypercholesterolemia, prevalence of tendon xanthomata, and occurrence of early coronary disease were indistinguishable from the other families studied. In summary, the data provide unequivocal evidence that a third locus can be etiological for monogenic familial hypercholesterolemia and should be reinvigorating to research in this field. 相似文献
4.
N. Rahman Fatima Abidi Deborah Ford Laura Arbour Elizabeth Rapley Patricia Tonin David Barton Gillian Batcup J. Berry Finbarr Cotter Val Davison Mary Gerrard Elizabeth Gray Richard Grundy Magdi Hanafy Derek King Ian Lewis Annette Ridolfi Luethy Lisa Madlensky Jill Mann Anne O’Meara Tony Oakhill Mark Skolnick Louise Strong Dick Variend Steven Narod Charles Schwartz Kathryn Pritchard-Jones Michael R. Stratton 《Human genetics》1998,103(5):547-556
A susceptibility gene for Wilms’ tumour (WT), designated FWT1, was previously mapped to chromosome 17q12–q21 by linkage analysis of a single family. We now confirm the existence of this
gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of
linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT
families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage
to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families
linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the
six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic
differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.
Received: 24 April 1998 / Accepted: 8 July 1998 相似文献
5.
Soragna D Vettori A Carraro G Marchioni E Vazza G Bellini S Tupler R Savoldi F Mostacciuolo ML 《American journal of human genetics》2003,72(1):161-167
Migraine is a common and disabling neurological disease of unknown origin characterized by a remarkable clinical variability. It shows strong familial aggregation, suggesting that genetic factors are involved in its pathogenesis. Different approaches have been used to elucidate this hereditary component, but a unique transmission model and causative gene(s) have not yet been identified. We report clinical and molecular data from a large Italian pedigree in which migraine without aura (MO) segregates as an autosomal dominant trait. After exclusion of any association between MO and the known familial hemiplegic migraine and migraine with aura loci, we performed a genomewide linkage analysis using 482 polymorphic microsatellite markers. We obtained significant evidence of linkage between the MO phenotype and the marker D14S978 on 14q22.1 (maximum two-point LOD score of 3.70, at a recombination fraction of 0.01). Multipoint parametric analysis (maximum LOD score of 5.25 between markers D14S976 and D14S978) and haplotype construction showed strong evidence of linkage in a region of 10 cM flanked by markers D14S1027 and D14S980 on chromosome 14q21.2-q22.3. These results indicate the first evidence of a genetic locus associated with MO on chromosome 14. 相似文献
6.
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
7.
Linkage analysis of familial Alzheimer disease, using chromosome 21 markers 总被引:11,自引:8,他引:3 下载免费PDF全文
Gerard D. Schellenberg Margaret A. Pericak-Vance Ellen M. Wijsman Deborah K. Moore Perry C. Gaskell Larry A. Yamaoka Jacqueline L. Bebout Leojean Anderson Kathleen A. Welsh Christopher M. Clark George M. Martin Allen D. Roses Thomas D. Bird 《American journal of human genetics》1991,48(3):563-583
Chromosome 21 markers were tested for linkage to familial Alzheimer disease (FAD) in 48 kindreds. These families had multiple cases of Alzheimer disease (AD) in 2 or more generations with family age-at-onset means (M) ranging from 41 to 83 years. Included in this group are seven Volga German families which are thought to be genetically homogeneous with respect to FAD. Autopsy documentation of AD was available for 32 families. Linkage to the 21 q11-q21 region was tested using D21S16, D21S13, D21S110, D21S1/S11, and the APP gene as genetic markers. When linkage results for all the families were summed, the LOD scores for these markers were consistently negative and the entire region was formally excluded. Linkage results were also summed for the following family groups; late-onset (M greater than 60), early-onset (M less than or equal to 60), Volga Germans (M = 56), and early-onset non-Volga Germans (M less than or equal to 60). For the first three groups, LOD scores were negative for this region. For the early-onset non-Volga German group (six families), small positive LOD scores of Zmax = 0.78 (recombination fraction theta = .15), Zmax = 0.27 (theta = .15), and Zmax = 0.64 (theta = .0), were observed for D21S13, D21S16, and D21S110, respectively. The remainder of the long arm of chromosome 21 was tested for linkage to FAD using seven markers spanning the q22 region. Results for these markers were also predominantly negative. Thus it is highly unlikely that a chromosome 21 gene is responsible for late-onset FAD and at least some forms of early-onset FAD represented by the Volga German kindreds. 相似文献
8.
Genetic heterogeneity in familial acute myelogenous leukemia: evidence for a second locus at chromosome 16q21-23.2. 总被引:1,自引:0,他引:1 下载免费PDF全文
M Horwitz K F Benson F Q Li J Wolff M F Leppert L Hobson M Mangelsdorf S Yu D Hewett R I Richards W H Raskind 《American journal of human genetics》1997,61(4):873-881
9.
Progressive familial intrahepatic cholestasis (PFIC) is the second most common form of familial intrahepatic cholestasis.
The genes for PFIC and for a milder form of the disease, benign recurrent intrahepatic cholestasis (BRIC), were recently mapped
to a 19-cM region on chromosome 18q21–q22. The results suggest that PFIC and BRIC are allelic diseases. We have studied 11
Swedish patients from eight families with clinical and biochemical features consistent with PFIC. The families were genotyped
for markers D18S69, D18S64, D18S55 and D18S68, spanning the PFIC candidate region. Unexpectedly, the segregation of haplotypes
excluded the entire region in three families, and no indications for shared haplotypes were found in the patients of the six
remaining families. A four-point linkage analysis of all families excluded linkage from D18S69 to D18S55 (Zmax < –5). Thus, our data strongly suggest the presence of a second, yet unknown, locus for PFIC. The results indicate that great
care should be taken when using 18q markers for prenatal diagnosis and genetic counseling for the disease.
Received: 12 February 1997 / Accepted: 11 April 1997 相似文献
10.
Kamel Ben Othmane Ellen Johnson Marisa Menold Felicia L. Graham Mongi Ben Hamida Osamu Hasegawa Allison D. Rogala Akio Ohnishi Margaret Pericak-Vance Faycal Hentati Jeffery M. Vance 《Genomics》1999,62(3):344
Autosomal recessive Charcot–Marie–Tooth disease type 4B (CMT4B) is a demyelinating hereditary motor and sensory neuropathy characterized by abnormal folding of myelin sheaths. A locus for CMT4B has previously been mapped to chromosome 11q23 in a southern Italian pedigree. We initially excluded linkage in two Tunisian families with CMT4B to chromosome 11q23, demonstrating genetic heterogeneity within the CMT4B phenotype. Subsequently, using homozygosity mapping and linkage analysis in the largest Tunisian pedigree, we mapped a new locus to chromosome 11p15. A maximum two-point lod score of 6.05 was obtained with the marker D11S1329. Recombination events refined the CMT4B locus region to a 5.6-cM interval between markers D11S1331 and D11S4194. The second Tunisian CMT4B family was excluded from linkage to the new locus, demonstrating the existence of at least a third locus for the CMT4B phenotype. 相似文献
11.
Identification of susceptibility genes for cancer in a genome-wide scan: results from the colon neoplasia sibling study 下载免费PDF全文
Daley D Lewis S Platzer P MacMillen M Willis J Elston RC Markowitz SD Wiesner GL 《American journal of human genetics》2008,82(3):723-736
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Americans and is the second leading cause of cancer mortality. Only a minority ( approximately 5%) of familial CRC can be explained by known genetic variants. To identify susceptibility genes for familial colorectal neoplasia, the colon neoplasia sibling study conducted a comprehensive, genome-wide linkage scan of 194 kindreds. Clinical information (histopathology, size and number of polyps, and other primary cancers) was used in conjunction with age at onset and family history for classification of the families into five phenotypic subgroups (severe histopathology, oligopolyposis, young, colon/breast, and multiple cancer) prior to analysis. By expanding the traditional affected-sib-pair design to include unaffected and discordant sib pairs, analytical power and robustness to type I error were increased. Sib-pair linkage statistics and Haseman-Elston regression identified 19 linkage peaks, with interesting results for chromosomes 1p31.1, 15q14-q22, 17p13.3, and 21. At marker D1S1665 (1p31.1), there was strong evidence for linkage in the multiple-cancer subgroup (p = 0.00007). For chromosome 15q14-q22, a linkage peak was identified in the full-sample (p = 0.018), oligopolyposis (p = 0.003), and young (p = 0.0009) phenotypes. This region includes the HMPS/CRAC1 locus associated with hereditary mixed polyposis syndrome (HMPS) in families of Ashkenazi descent. We provide compelling evidence linking this region in families of European descent with oligopolyposis and/or young age at onset (相似文献
12.
N G Laing B A Laing C Meredith S D Wilton P Robbins K Honeyman S Dorosz H Kozman F L Mastaglia B A Kakulas 《American journal of human genetics》1995,56(2):422-427
We have studied a family segregating a form of autosomal dominant distal myopathy (MIM 160500) and containing nine living affected individuals. The myopathy in this family is closest in clinical phenotype to that first described by Gowers in 1902. A search for linkage was conducted using microsatellite, VNTR, and RFLP markers. In total, 92 markers on all 22 autosomes were run. Positive linkage was obtained with 14 of 15 markers tested on chromosome 14, with little indication of linkage elsewhere in the genome. Maximum two-point LOD scores of 2.60 at recombination fraction .00 were obtained for the markers MYH7 and D14S64--the family structure precludes a two-point LOD score > or = 3. Recombinations with D14S72 and D14S49 indicate that this distal myopathy locus, MPD1, should lie between these markers. A multipoint analysis assuming 100% penetrance and using the markers D14S72, D14S50, MYH7, D14S64, D14S54, and D14S49 gave a LOD score of exactly 3 at MYH7. Analysis at a penetrance of 80% gave a LOD score of 2.8 at this marker. This probable localization of a gene for distal myopathy, MPD1, on chromosome 14 should allow other investigators studying distal myopathy families to test this region for linkage in other types of the disease, to confirm linkage or to demonstrate the likely genetic heterogeneity. 相似文献
13.
Zhicheng J Lihe L Zhiyan H Xiansheng C Yubao Z Yuejin Y Rutai H 《Biochemical and biophysical research communications》2004,315(4):1033-1038
A four-generation pedigree of familial primary pulmonary hypertension (FPPH) with 14 alive members was collected. In the family, three of the 14 alive familial members were diagnosed as FPPH. Mutations in bone morphogenetic protein receptor-II (BMPR-II) gene were screened by using sequencing analysis. A C-to-T transition at position 1471 in exon 11 of the BMPR-II gene was identified, resulting in an Arg491Trp mutation. We confirmed segregation of the mutation within the family and excluded the presence of the mutations in a panel of 240 chromosomes from normal individuals. No mutations were found in BMPR-II gene in other 10 patients with sporadic primary pulmonary hypertension. The Arg491Trp mutation is located in the kinase domain and predicted to disturb the kinase activity of BMPR-II. Total 7 familial members died at age 8-45 years with various symptoms, indicating other genetic or environmental modifiers involved in the modification of the clinical phenotype. 相似文献
14.
Identification of microdeletions spanning the Diamond-Blackfan anemia locus on 19q13 and evidence for genetic heterogeneity. 总被引:8,自引:0,他引:8 下载免费PDF全文
P Gustavsson E Garelli N Draptchinskaia S Ball T N Willig D Tentler I Dianzani H H Punnett F E Shafer H Cario U Ramenghi A Glomstein R A Pfeiffer A Goringe N F Olivieri E Smibert G Tchernia G Elinder N Dahl 《American journal of human genetics》1998,63(5):1388-1395
Diamond-Blackfan anemia (DBA) is a rare pure red-cell hypoplasia of unknown etiology and pathogenesis. A major DBA locus has previously been localized to chromosome 19q13.2. Samples from additional families have been collected to identify key recombinations, microdeletions, and the possibility of heterogeneity for the disorder. In total, 29 multiplex DBA families and 50 families that comprise sporadic DBA cases have been analyzed with polymorphic 19q13 markers, including a newly identified short-tandem repeat in the critical gene region. The results from DNA analysis of 29 multiplex families revealed that 26 of these were consistent with a DBA gene on 19q localized to within a 4.1-cM interval restricted by loci D19S200 and D19S178; however, in three multiplex families, the DBA candidate region on 19q13 was excluded from the segregation of marker alleles. Our results suggest genetic heterogeneity for DBA, and we show that a gene region on chromosome 19q segregates with the disease in the majority of familial cases. Among the 50 families comprising sporadic DBA cases, we identified two novel and overlapping microdeletions on chromosome 19q13. In combination, the three known microdeletions associated with DBA restrict the critical gene region to approximately 1 Mb. The results indicate that a proportion of sporadic DBA cases are caused by deletions in the 19q13 region. 相似文献
15.
Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. 下载免费PDF全文
P F Worth P Giunti C Gardner-Thorpe P H Dixon M B Davis N W Wood 《American journal of human genetics》1999,65(2):420-426
Autosomal dominant cerebellar ataxia type III (ADCA III) is a relatively benign, late-onset, slowly progressive neurological disorder characterized by an uncomplicated cerebellar syndrome. Three loci have been identified: a moderately expanded CAG trinucleotide repeat in the SCA 6 gene, the SCA 5 locus on chromosome 11, and a third locus on chromosome 22 (SCA 10). We have identified two British families in which affected individuals do not have the SCA 6 expansion and in which the disease is not linked to SCA 5 or SCA 10. Both families exhibit the typical phenotype of ADCA III. Using a genomewide searching strategy in one of these families, we have linked the disease phenotype to marker D15S1039. Construction of haplotypes has defined a 7.6-cM interval between the flanking markers D15S146 and D15S1016, thereby assigning another ADCA III locus to the proximal long-arm of chromosome 15 (SCA 11). We excluded linkage of the disease phenotype to this region in the second family. These results indicate the presence of two additional ADCA III loci and more clearly define the genetic heterogeneity of ADCA III. 相似文献
16.
Gerard D. Schellenberg Haydeh Payami Ellen M. Wijsman Harry T. Orr Katrina A. B. Goddard Leojean Anderson Ellen Nemens June A. White M. Elisa Alonso Melvyn J. Ball Jeffrey Kaye John C. Morris Helena Chui A. Dessa Sadovnick Leonard L. Heston George M. Martin Thomas D. Bird 《American journal of human genetics》1993,53(3):619-628
Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analyses were used, in 49 families with a mean age at onset ≥60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score ≤ –2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P < .02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset ≥60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 相似文献
17.
Investigation of a Family with Autosomal Dominant Dilated Cardiomyopathy Defines a Novel Locus on Chromosome 2q14-q22 总被引:4,自引:0,他引:4 下载免费PDF全文
Martin Jung Imke Poepping Andreas Perrot Annette E. Ellmer Thomas F. Wienker Rainer Dietz André Reis Karl Josef Osterziel 《American journal of human genetics》1999,65(4):1068-1077
Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the most frequent indication for heart transplantation in young patients. Probably >25% of DCM cases are of familial etiology. We report here genetic localization in a three-generation German family with 12 affected individuals with autosomal dominant familial DCM characterized by ventricular dilatation, impaired systolic function, and conduction disease. After exclusion of known DCM loci, we performed a whole-genome screen and detected linkage of DCM to chromosome 2q14-q22. Investigation of only affected individuals defines a 24-cM interval between markers D2S2224 and D2S2324; when unaffected individuals are also included, the critical region decreases to 11 cM between markers D2S2224 and D2S112, with a peak LOD score of 3.73 at recombination fraction 0 at D2S2339. The identification of an additional locus for familial autosomal dominant DCM underlines the genetic heterogeneity and may assist in the elucidation of the causes of this disease. 相似文献
18.
Autosomal dominant familial spastic paraplegia: reduction of the FSP1 candidate region on chromosome 14q to 7 cM and locus heterogeneity. 总被引:8,自引:3,他引:5 下载免费PDF全文
S Gispert N Santos R Damen T Voit J Schulz T Klockgether G Orozco F Kreuz J Weissenbach G Auburger 《American journal of human genetics》1995,56(1):183-187
Three large pedigrees of German descent with autosomal dominant "pure" familial spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype and linkage analyses, with microsatellites covering the FSP region on chromosome 14q (locus FSP1), were performed. In pedigree W, we found a haplotype that cosegregates with the disease and observed three crossing-over events, reducing the FSP1 candidate region to 7 cM; in addition, the observation of apparent anticipation in this family suggests a trinucleotide repeat expansion as the mutation. In pedigrees D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. 相似文献
19.
T C Hart D Pallos D W Bowden J Bolyard M J Pettenati J R Cortelli 《American journal of human genetics》1998,62(4):876-883
Gingival fibromatosis is characterized by a slowly progressive benign enlargement of the oral gingival tissues. The condition results in the teeth being partially or totally engulfed by keratinized gingiva, causing aesthetic and functional problems. Both genetic and pharmacologically induced forms of gingival fibromatosis are known. The most common genetic form, hereditary gingival fibromatosis (HGF), is usually transmitted as an autosomal dominant trait, although sporadic cases are common and autosomal recessive inheritance has been reported. The genetic basis of gingival fibromatosis is unknown. We identified an extended family (n=32) segregating an autosomal dominant form of isolated gingival fibromatosis. Using a genomewide search strategy, we identified genetic linkage (Zmax=5.05, straight theta=.00) for the HGF phenotype to polymorphic markers in the genetic region of chromosome 2p21 bounded by the loci D2S1788 and D2S441. This is the first report of linkage for isolated HGF, and the findings have implications for identification of the underlying genetic basis of gingival fibromatosis. 相似文献
20.
Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity. 总被引:18,自引:0,他引:18
M P Winn P J Conlon K L Lynn D N Howell B D Slotterbeck A H Smith F L Graham M Bembe L D Quarles M A Pericak-Vance J M Vance 《Genomics》1999,58(2):113-120
Focal segmental glomerulosclerosis (FSGS) is a pathological entity characterized by proteinuria, nephrotic syndrome, and the progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD). Recently, familial forms of FSGS have been identified. Two families with autosomal dominant FSGS were evaluated for linkage using 351 genomic microsatellite markers. Linkage, multipoint analysis, and tests for heterogeneity were performed on the subsequent results. In addition, three small families were used for haplotype analysis. Evidence for linkage was found on chromosome 11q21-q22 for the largest family, with a maximum lod score of 9.89. The gene is currently localized to an 18-cM area between flanking markers D11S2002 and D11S1986. The disease in a second family was not linked to this locus or to a previously described locus on chromosome 19q13. There were no shared haplotypes among affected individuals in the three smaller families. Our findings demonstrate that genetic heterogeneity is prevalent in FSGS in that at least three genes cause the FSGS phenotype. Identification of the genes that cause familial FSGS will provide valuable insights into the molecular basis and pathophysiology of FSGS. 相似文献