The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. The symptoms are generally refractory to treatment and persist throughout life. Five kindreds with multiple cases of primary erythermalgia were identified, and the largest was subjected to a genomewide search. We detected strong evidence for linkage of the primary erythermalgia locus to markers from chromosome 2q. The highest LOD score (Z) was obtained with D2S2330 (Z(max) = 6.51). Analysis of recombination events identified D2S2370 and D2S1776 as flanking markers, on chromosome 2q31-32. This defines a critical interval of 7.94 cM that harbors the primary erythermalgia gene. Affected members within the additional families also shared a common haplotype on chromosome 2q31-32, supporting our linkage results. Identification of the primary erythermalgia gene will allow a better clinical classification of this pleomorphic group of disorders.     

Human gene for torsion dystonia located on chromosome 9q32-q34

Torsion dystonia is a movement disorder of unknown etiology characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Dystonic movements can be caused by lesions in the basal ganglia, drugs, or gene defects. Several hereditary forms have been described, most of which have autosomal dominant transmission with variable expressivity. In the Ashkenazi Jewish population the defective gene frequency is about 1/10,000. Here, linkage analysis using polymorphic DNA and protein markers has been used to locate a gene responsible for susceptibility to dystonia in a large, non-Jewish kinship. Affected members of this family have a clinical syndrome similar to that found in the Jewish population. This dystonia gene (ITD1) shows tight linkage with the gene encoding gelsolin, an actin binding protein, and appears by multipoint linkage analysis to lie in the q32-q34 region of chromosome 9 between ABO and D9S26, a region that also contains the locus for dopamine-beta-hydroxylase.     

The gene cluster for human U2 RNA is located on chromosome 17q21

The gene cluster for human U2 RNA has been mapped to chromosome 17q21 by in situ hybridization and hybridization analysis of DNA from mouse/human somatic cell hybrids.     

Evidence for an association between nonsyndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4.

Recent studies suggest that the familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL +/- P) is likely to be attributable to the effects of several susceptibility loci, acting in a multiplicative fashion. Two potential CL +/- P susceptibility loci (CSL), transforming growth factor alpha (TGFA) and retinoic acid receptor (RARA), have been identified through association studies. In addition, recent evidence of linkage between CL +/- P and two markers (D4S175 and D4S192) in the region 4q25-4q31.3 raised the possibility that a CSL, with a larger effect than either TGFA or RARA, may reside within this region of the human genome. The present analyses were undertaken to determine whether D4S175 or D4S192 is significantly associated with CL +/- P in a sample of unrelated patients that have previously provided evidence of associations between CL +/- P and both TGFA and RARA. The results of these analyses provide further, tentative, evidence for the presence of a CSL locus on the long arm of chromosome 4 and help to refine the location of this locus in the region of D4S175 and D4S192.     

A major susceptibility locus influencing plasma triglyceride concentrations is located on chromosome 15q in Mexican Americans

Although several genetic forms of rare or syndromic hypertriglyceridemia have been reported, little is known about the specific chromosomal regions across the genome harboring susceptibility genes for common forms of hypertriglyceridemia. Therefore, we conducted a genomewide scan for susceptibility genes influencing plasma triglyceride (TG) levels in a Mexican American population. We used both phenotypic and genotypic data from 418 individuals distributed across 27 low-income, extended Mexican American families. For the analyses, TG values were log transformed (ln TG). We used a variance-components technique to conduct multipoint linkage analyses for localizing susceptibility genes that determine variation in TG levels. We used an approximately 10-15-cM map, which was made on the basis of information from 295 microsatellite markers. After accounting for the effects of sex and sex-specific age terms, we found significant evidence for linkage (LOD = 3.88) of ln TG levels to a genetic location between the markers GABRB3 and D15S165 on chromosome 15q. This putative locus explains 39.7+/-7% (P=.000012) of total phenotypic variation in ln TG levels. Suggestive evidence was found for linkage of ln TG levels to two different locations on chromosome 7, which are approximately 85 cM apart from each other. Also, there is some evidence for linkage of high-density lipoprotein cholesterol concentrations to a genetic location near one of the regions on chromosome 7. In conclusion, we found strong evidence for linkage of ln TG levels to a genetic location on chromosome 15q in a Mexican American population, which is prone to disease conditions such as type 2 diabetes and the insulin-resistance syndrome that are associated with hypertriglyceridemia. This putative locus appears to have a major influence on ln TG variation.     

A susceptibility locus for bipolar affective disorder on chromosome 4q35.

Bipolar affective disorder (BAD) affects approximately 1% of the population and shows strong heritability. To identify potential BAD susceptibility loci, we undertook a 15-cM genome screen, using 214 microsatellite markers on the 35 most informative individuals of a large, statistically powerful pedigree. Data were analyzed by parametric two-point linkage methods under several diagnostic models. LOD scores >1.00 were obtained for 21 markers, with four of these >2.00 for at least one model. The remaining 52 individuals in the family were genotyped with these four markers, and LOD scores remained positive for three markers. A more intensive screen was undertaken in these regions, with the most positive results being obtained for chromosome 4q35. Using a dominant model of inheritance with 90% maximum age-specific penetrance and including bipolar I, II, schizoaffective/mania, and unipolar individuals as affected, we obtained a maximum two-point LOD score of 2.20 (theta = .15) at D4S1652 and a maximum three-point LOD score of 3.19 between D4S408 and D4S2924. Nonparametric analyses further supported the presence of a locus on chromosome 4q35. A maximum score of 2.62 (P=.01) was obtained between D4S1652 and D4S171 by use of the GENEHUNTER program, and a maximum score of 3.57 (P=.0002) was obtained at D4S2924 using the affected pedigree member method. Analysis of a further 10 pedigrees suggests the presence of this locus in at least one additional family, indicating a possible predisposing locus and not a pedigree-specific mutation. Our results suggest the presence of a novel BAD susceptibility locus on chromosome 4q35.     

A susceptibility locus for migraine with aura, on chromosome 4q24

Migraine is a complex neurovascular disorder with substantial evidence supporting a genetic contribution. Prior attempts to localize susceptibility loci for common forms of migraine have not produced conclusive evidence of linkage or association. To date, no genomewide screen for migraine has been published. We report results from a genomewide screen of 50 multigenerational, clinically well-defined Finnish families showing intergenerational transmission of migraine with aura (MA). The families were screened using 350 polymorphic microsatellite markers, with an average intermarker distance of 11 cM. Significant evidence of linkage was found between the MA phenotype and marker D4S1647 on 4q24. Using parametric two-point linkage analysis and assuming a dominant mode of inheritance, we found for this marker a maximum LOD score of 4.20 under locus homogeneity (P=.000006) or locus heterogeneity (P=.000011). Multipoint parametric (HLOD = 4.45; P=.0000058) and nonparametric (NPL(all) = 3.43; P=.0007) analyses support linkage in this region. Statistically significant linkage was not observed in any other chromosomal region.     

Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage.

We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P相似文献   

The human QARS locus: assignment of the human gene for glutaminyl-tRNA synthetase to chromosome 1q32–42

Summary We have used a cDNA encoding the core region of the human glutaminyl-tRNA synthetase to determine the chromosomal localization of the corresponding gene. Southern blots of restricted DNA from a panel of rodent-human cell lines and in situ chromosome hybridization gave identical results showing that the human gene locus for glutaminyl-tRNA synthetase resides on the distal long arm of chromosome 1. There are now nine mapped aminoacyl-tRNA synthetase genes in the human genome.     

A sequence-ready 840-kb PAC contig spanning the candidate tumor suppressor locus DBC1 on human chromosome 9q32-q33.

A putative tumor suppressor locus involved in bladder cancer has been mapped to human chromosome 9q32-q33 and designated DBC1. Our previous microsatellite-based deletion mapping study indicated that DBC1 was localized between D9S1848 and AFMA239XA9. We have constructed an 840-kb sequence-ready contig composed of bacteriophage P1-derived artificial chromosomes (PACs), which encompasses DBC1. Clones were initially identified by screening a PAC library with markers localized to the region by physical mapping, and subsequently PAC end probes were used to complete the contig. This contig contains a minimum tiling path of six PAC clones between D9S1848 and AFMA239XA9. Three expressed sequence tags (ESTs) were mapped to the DBC1 region by screening 24 ESTs mapped to the surrounding area by radiation hybrids. One represented the gene for DBCCR1, a known candidate for DBC1, and the other two were novel. This contig and preliminary expression map form the basis for the identification of the bladder cancer tumor suppressor gene in this region.     

beta2-microglobulin locus on human chromosome 15.

We have developed an autoradiographic/electrophoretic assay capable of distinguishing mouse and human beta2-microglobulin (beta2m) in spent culture media. The method is applicable to mouse and human lines and to hybrid cell lines made from them. With this technique, mouse/human hybrid cell lines were tested for the presence of human beta2m. Isozyme and karyotype analyses were also carried out with the hybrids. The combined results of these studies show that the structural gene for human beta2m is on the long arm of chromosome 15.     

A locus for hereditary capillary malformations mapped on chromosome 5q

Capillary malformations (port-wine stains) are the most common vascular malformations occurring in 0.3% of live births. Most capillary malformations occur sporadically and present as a solitary lesion. Capillary malformations can also occur as a component of well-described syndromes. Familial occurrence of multiple capillary malformations has been described in the literature, suggesting autosomal dominant inheritance with variable expression in this subgroup. A hereditary basis underlying the development of solitary capillary malformations has not been found, but may well be possible. We have mapped a locus for an autosomal dominant disorder in a three-generation family that manifested itself with multiple cutaneous capillary malformations to chromosome 5q13-22. This locus spans 48 cM between the markers D5S647 and D5S659 and harbours several candidate genes. By defining the gene(s) responsible for capillary malformations, we will gain more insight in the pathogenesis of this disorder. It is likely that genes implicated in these familial cases may be involved in the more sporadic cases.     

A new locus for autosomal dominant pure spastic paraplegia, on chromosome 2q24-q34

Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous disorders causing progressive spasticity and weakness of the lower limbs. We report a large family of French descent with autosomal dominant pure HSP. We excluded genetic linkage to the known loci causing HSP and performed a genomewide search. We found evidence for linkage of the disorder to polymorphic markers on chromosome 2q24-q34: a maximum LOD score of 3. 03 was obtained for marker D2S2318. By comparison with families having linkage to the major locus of pure autosomal dominant HSP (SPG4 on chromosome 2p), there were significantly more patients without Babinski signs, with increased reflexes in the upper limbs, and with severe functional handicaps.     

A new susceptibility locus for autosomal dominant pancreatic cancer maps to chromosome 4q32-34

Pancreatic cancer is the fifth leading cause of cancer death in the United States. Nearly every person diagnosed with pancreatic cancer will die from it, usually in <6 mo. Familial clustering of pancreatic cancers is commonly recognized, with an autosomal dominant inheritance pattern in approximately 10% of all cases. However, the late age at disease onset and rapid demise of affected individuals markedly hamper collection of biological samples. We report a genetic linkage scan of family X with an autosomal dominant pancreatic cancer with early onset and high penetrance. For the study of this family, we have developed an endoscopic surveillance program that allows the early detection of cancer and its precursor, before family members have died of the disease. In a genomewide screening of 373 microsatellite markers, we found significant linkage (maximum LOD score 4.56 in two-point analysis and 5.36 in three-point analysis) on chromosome 4q32-34, providing evidence for a major locus for pancreatic cancer.     

定位于5q31-5q32的DFNA52的20个候选基因的突变筛查

为了克隆定位于5号染色体微卫星标记D5S2056和D5S638之间约8.8 cM的区间内的非综合征性常染色体显性遗传性耳聋 DFNA52 (OMIM: 607683)的致病基因, 文章根据基因在耳蜗组织的表达情况, 筛选出20个候选基因, 设计合成了扩增20个基因外显子及外显子与内含子交界的引物, 用DNA直接测序法进行序列变异分析。结果显示, 在基因外显子及侧翼区共发现了45个单核苷酸多态, 其中42个变异在多态数据库已报道, 其余3个为新发现的单核苷酸多态, 序列变异与疾病表型无共分离现象, 排除了这些基因外显子突变导致遗传性耳聋的可能性。