SEARCH · Search PubMed

Results for “Data Linkage”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

PubMedDate not supplied

Confidence limits for estimates of gene linkage based on analysis of recombinant inbred strains.

Recombinant inbred (RI) strains are extremely useful for genetic mapping. This paper presents a simple method for determining confidence intervals for linkage estimates based on analysis of RI strains. The results show that such confidence intervals are usually large with the currently available numbers of RI strains. Therefore, map positions based only on analysis of RI strains should be interpreted with caution. To facilitate interpretation of linkage data derived from RI strains, a table is presented giving the 95 percent and 99 percent confidence intervals for all possible linkages detected with up to 45 RI strains.

Animals↗

PubMed2000

Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis.

OBJECTIVE: To examine 11 candidate genes as susceptibility loci for osteoarthritis (OA). METHODS: A total of 481 families have been ascertained in which at least two siblings have had joint replacement surgery of the hip, or knee, or hip and knee for idiopathic OA. Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker. The linkage data were analysed unstratified and following stratification by sex and by joint replaced (hip or knee). RESULTS: The analyses revealed suggestive linkage of the type IX collagen gene COL9A1 (6q12-q13) to a subset of 132 families that contained affected females who were concordant for hip OA (female-hip) with a P-value of 0.00053 and logarithm of the odds (LOD) score of 2.33 [corrected P-value of 0. 0016, corrected LOD score of 1.85]. CONCLUSIONS: COL9A1 may therefore be a susceptibility locus for female hip OA. In addition, there was weak evidence of linkage to HLA/COL11A2 (6p21.3) in female hip OA with a corrected P-value of 0.016.

Arthroplasty, Replacement↗

PubMed1993

The chromosome 6p epilepsy locus: exploring mode of inheritance and heterogeneity through linkage analysis.

Juvenile myoclonic epilepsy (JME) is a common form of adolescent-onset, generalized epilepsy. JME is genetically linked to the HLA locus on chromosome 6. Families of JME patients also have a significant recurrence of other forms of generalized epilepsy. We used the linkage data to investigate the mode of inheritance of JME and the associated electroencephalographic (EEG) traits at the HLA-linked locus. We investigated how robust the linkage results were when we changed the assumptions of mode of inheritance and penetrance and whether absence and clonic-tonic-clonic in JME families are influenced by the same gene locus as JME. Our results show that the finding of linkage is stable within a wide range of assumptions of penetrance and mode of inheritance, and that the EEG traits seen in unaffected family members reflect the actions of the same gene that is involved in the expression of JME. Our data also suggest that the same locus is responsible for non-JME forms of epilepsy seen in JME families, and that either different doses of the disease allele at the JME locus may lead to different epilepsy phenotypes or that another locus influences the final disease phenotype.

Adolescent↗

PubMed2006

Genome-wide linkage analysis of population variation in high-density lipoprotein cholesterol.

Lower plasma levels of high-density lipoprotein cholesterol (HDL-C) are associated with the metabolic syndrome (insulin resistance, obesity, hypertension) and higher cardiovascular risk. Recent association studies have suggested rare alleles responsible for very low HDL-C levels. However, for individual cardiovascular risk factors, the majority of population-attributable deaths are associated with average rather than extreme levels. Therefore, genetic factors that determine the population variation of HDL-C are particularly relevant. We undertook genome-wide and fine mapping to identify linkage to HDL-C in healthy adult nuclear families from the Victorian Family Heart Study. In 274 adult sibling pairs (average age 24 years, average plasma HDL-C 1.4 mmol/l), genome-wide mapping revealed suggestive evidence for linkage on chromosome 4 (Z score = 3.5, 170 cM) and nominal evidence for linkage on chromosomes 1 (Z = 2.1, 176 cM) and 6 (Z = 2.6, 29 cM). Using genotypes and phenotypes from 932 subjects (233 of the sibling pairs and their parents), finer mapping of the locus on chromosome 4 strengthened our findings with a peak probability (Z score = 3.9) at 169 cM. Our linkage data suggest that chromosome 4q32.3 is linked with normal population variation in HDL-C. This region coincides with previous reports of linkage to apolipoprotein AII (a major component of HDL) and encompasses the gene encoding the carboxypeptidase E, relevant to the metabolic syndrome and HDL-C. These findings are relevant for further understanding of the genetic determinants of cardiovascular risk at a population level.

Adult↗

PubMed2004

Fine mapping of 16q-linked autosomal dominant cerebellar ataxia type III in Japanese families.

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. To date, at least 11 genes and 13 additional loci have been identified in ADCAs. Despite phenotypic differences, spinocerebellar ataxia 4 (SCA4) and Japanese 16q-linked ADCA type III map to the same region of 16q22.1. We report four Japanese families with pure cerebellar ataxia and a disease locus at 16q22.1. Our families yielded a peak lod score of 6.01 at marker D16S3141. To refine the candidate region, we carried out genetic linkage studies in four pedigrees with a high density set of DNA markers from chromosome 16q22.1. Our linkage data suggest that the disease locus for 16q-ADCA type III is within the 1.25-Mb interval delineated by markers 17msm and CTTT01. We screened for mutations in 36 genes within the critical region. Our critical region lies within the linkage interval reported for SCA4 and for Japanese 16q-ADCA type III. These data suggest that the ADCA that we have characterized is allelic with SCA4 and Japanese 16q-linked ADCA type III.

Alleles↗

PubMedDate not supplied

Gene for non-specific X-linked mental retardation maps in the pericentromeric region.

Linkage analysis was carried out in a large four-generation German family segregating for non-specific X-linked mental retardation. Affected males have moderate intellectual handicap. Speech delay, deviant behaviour, and hyperactivity have also been reported. Head circumference and testicular volumes are normal. Cytogenetic analysis failed to show evidence for fragile site or structural abnormality of the X chromosome. None of the obligatory carriers shows any clinical symptoms. Close linkage without recombination (lod scores 1.74 to 2.05) has been found between the disease locus (MRX1) and the polymorphic DNA loci DXS7 (Xp11.4-p11.3), MAOA (Xp11.3-p11.23), DXS255 (Xp11.22), and DXS159 (Xq12) suggesting that the gene responsible for the disease in this family maps in the pericentromeric region of the X chromosome. Linkage data obtained with the flanking marker loci OTC (Xp21.1) and DXS95 (Xq21.2-q21.3) also were compatible with this localization of the MRX1 gene. Close linkage to loci from Xp22, Xq22, Xq24-25, or Xq28 could be excluded.

Adult↗

PubMed1993

Susceptibility genes for familial Alzheimer's disease on chromosomes 19 and 21: a reality check.

Linkage data from 92 FAD kindreds were analyzed by lod score analysis under various assumptions of disease penetrance, marker allele frequencies, and heterogeneity. Multilocus linkage analysis supports the existence of a gene in 40%-65% of families with predominantly late-onset illness (after age 65) on chromosome 19 between D19S13 and ATP1A3. Evidence for a second FAD gene on chromosome 21 is weaker and stems primarily from a few families with early-onset disease. Our findings also indicate that choice of the genetic model for FAD and marker allele frequencies may be crucial to conclusions about linkage and heterogeneity.

Aged↗

PubMed1976

Comparative mapping using somatic cell hybrids.

Comparative mapping, or ascertaining the gene linkage relationships between different species, is rapidly developing. This is possible because new techniques in chromosome identification and somatic cell hybridization, such as the generation of hybrids preferentially segregating chromosomes of any desired species including rodents, and the development of gene transfer techniques have yielded new information about the human and rodent gene maps. In addition, the discovery and characterization of mouse subspecies has generated new mouse sexual genetic linkage data. The following picture is emerging. Several X-linked genes in man are X-linked in all mammalian species tested. The linkage relationships of several tightly linked genes, less than 1 map unit apart, are also conserved in all mammalian species tested. Ape autosomal genes are assigned to ape chromosomes homologous to their human counterparts indicating extensive conservation in the 12 million years (MYR) of evolution from apes to man. Similarly, mouse and rat, 10 MYR apart in evolution, have several large autosomal synteny groups conserved. In comparing the mouse and human gene maps we find that human genes assigned to different arms of the same human chromosome are unlinked in the mouse; mouse genes large map distances (20 to 45 cM) apart are very likely to be unlinked in the human. However, several autosomal synteny groups 10 to 20 cM apart, including the Pgd, Eno-1, Pgm-1 group on human chromosome arm 1p, are conserved in mice and man. This suggests that homology mapping, the superimposition of one species gene map on the homologous conserved portion of another species genome may be possible, and that ancestral autosomal synteny groups should be detectable.

Animals↗

PubMed1997

The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2.

The activin receptor-like kinase 1 gene (ALK-1) is the second locus for the autosomal dominant vascular disease hereditary hemorrhagic telangiectasia (HHT). In this paper we present the genomic structure of the ALK-1 gene, a type I serine-threonine kinase receptor expressed predominantly in endothelial cells. The coding region is contained within nine exons, spanning < 15 kb of genomic DNA. All introns follow the GT-AG rule, except for intron 6, which has a TAG/gcaag 5' splice junction. The positions of introns in the intracellular domain are almost identical to those of the mouse serine-threonine kinase receptor TSK-7L. By sequencing ALK-1 from genomic DNA, mutations were found in six of six families with HHT either shown to link to chromosome 12q13 or in which linkage of HHT to chromosome 9q33 had been excluded. Mutations were also found in three of six patients from families in which available linkage data were insufficient to allow certainty with regard to the locus involved. The high rate of detection of mutations by genomic sequencing of ALK-1 suggests that this will be a useful diagnostic test for HHT2, particularly where preliminary linkage to chromosome 12q13 can be established. In two cases in which premature termination codons were found in genomic DNA, the mutant mRNA was either not present or present at barely detectable levels. These data suggest that mutations in ALK-1 are functionally null alleles.

Activin Receptors↗

PubMed2002

Research use of linked health data--a best practice protocol.

OBJECTIVE: This article outlines a protocol for facilitating access to administrative data for the purpose of health services research, when these data are sourced from multiple organisations. This approach is designed to promote confidence in the community and among data custodians that there are benefits of linked health information being used and that individual privacy is being rigorously protected. BACKGROUND: Linked health administration data can provide an unparalleled resource for the monitoring and evaluation of health care services. However, for a number of reasons, these data have not been readily available to researchers. In Australia, an additional barrier to research is the result of health data sets being collected by different levels of government - thus all are not available to any one authority. To improve this situation, a practical blue-print for the conduct of data linkage is proposed. This should provide an approach suitable for most projects that draw large volumes of information from multiple sources, especially when this includes organisations in different jurisdictions. CONCLUSIONS AND IMPLICATIONS: Health data, although widely and diligently collected, continue to be under-utilised for research and evaluation in most countries. This protocol aims to make these data more easily available to researchers by providing a controlled and secure mechanism that guarantees privacy protection.

Access to Information↗

PubMed2001

Linkage mapping of a nonspecific form of X-linked mental retardation (MRX53) in a large Pakistani family.

Nonspecific X-linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X-linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2-26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081.

Chromosome Mapping↗

PubMed1987

Demonstration of an altered phenylalanyl-tRNA synthetase in an analogue-resistant mutant of Aspergillus nidulans.

We have isolated and characterized a new class of p-fluorophenylalanine (FPA)-resistant mutant in Aspergillus nidulans using a phenA strain as the wild type, by optimizing the conditions of growth. All four spontaneous mutants selected on a medium containing FPA were found to be recessive to their wild-type alleles in heterozygous diploids. Complementation analyses and linkage data showed that they were allelic and mapped at a single locus (fpaU) in the facA-riboD interval on the right arm of linkage group V. Partial purification and characterization of Phe-tRNA synthetase from wild-type and mutant strains revealed that the mutant enzyme had a greatly reduced ability to activate the analogue. It is suggested that mutation in the fpaU gene brings about a structural alteration in Phe-tRNA synthetase.

Amino Acyl-tRNA Synthetases↗

PubMed1992

Linkage studies of Usher syndrome type 1: exclusion results from the Usher syndrome consortium.

Usher Syndrome Type 1 is an autosomal recessive disease characterized by profound congenital hearing impairement and vestibular dysfunction followed by the onset of retinitis pigmentosa in childhood or early adolescence. Members of the Usher Syndrome Consortium, whose objective is to locate and isolate the genes for Usher syndrome, have pooled linkage data from 36 families with 111 affected individuals. We report the analysis of 206 blood group, protein, and DNA marker polymorphisms. No evidence of linkage heterogeneity among families was found for any of the markers studied; the negative lod scores exclude the locus for this disease from about 39% of the genome. Our results indicate the regions of the genome to which our continuing efforts should be directed.

Chromosome Mapping↗

PubMed1997

The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin.

OBJECTIVE: To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia. DESIGN: Economic benefit analysis based on data from the West of Scotland coronary prevention study. Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated. Scottish record linkage data provided disease specific survival. Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotland coronary prevention study. SUBJECTS: Men with hypercholesterolaemia similar to the subjects in the West of Scotland coronary prevention study. MAIN OUTCOME: Cost consequences, the number of transitions from health to cardiovascular disease prevented, the number needed to start treatment, and cost per life year gained. RESULTS: If 10,000 of these men started taking pravastatin, 318 of them would not make the transition from health to cardiovascular disease (number needed to treat, 31.4), at a net discounted cost of 20m Pounds over 5 years. These benefits imply an undiscounted gain of 2,460 years of life, and thus 8121 Pounds per life year gained, or 20,375 Pounds per life year gained if benefits are discounted. Restriction to the 40% of men at highest risk reduces the number needed to treat to 22.5 (5601 Pounds per life year gained (undiscounted) and 13,995 Pounds per life year gained (discounted)). CONCLUSIONS: In subjects without evidence of prior myocardial infarction but who have hypercholesterolaemia, the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups.

Anticholesteremic Agents↗

PubMed2003

Register based monitoring shows decreasing socioeconomic differences in Finnish perinatal health.

STUDY OBJECTIVE: Several studies on differences in infant outcome by socioeconomic position have been done, but these have usually been based on ad hoc data linkages. The aim of this paper was to investigate whether socioeconomic differences in perinatal health in Finland could be regularly monitored using routinely collected data from one single register. DESIGN AND SETTING: Since October 1990, the Finnish Medical Birth Register (MBR) has included data on maternal occupation. A special computer program that converted the occupation name into an occupational code and into a socioeconomic position was prepared. Perinatal health was measured with five different indicators. The Finnish MBR data for years 1991 to 1999 (n=565 863 newborns) were used in the study. The study period was divided into three, three year periods to study time trends. RESULTS: An occupational code was derived for 95% of women, but it was not possible to define a socioeconomic position for 22% of women, including, for example, students and housewives (the group "Others"). For the rest, the data showed socioeconomic differences in all perinatal health indicators. Maternal smoking explained up to half of the excess risk for adverse perinatal outcome in the lowest socioeconomic group. The socioeconomic differences narrowed during the 1990s: infant outcome improved in the lowest socioeconomic group, but remained at the same level or even deteriorated in other groups. When comparing the lowest group with the highest group, the odds ratios (OR) adjusted for maternal background characteristics at least halved for prematurity (from 1.32 (95% confidence intervals 1.24 to 1.43) in 1991-1993 to 1.16 (1.08 to 1.25) in 1997-1999), for low birth weight (from 1.49 (1.36 to 1.63) to 1.25 (1.17 to 1.40)), and for perinatal mortality (from 1.79 (1.44 to 2.21) to 1.33 (1.07 to 1.66)). CONCLUSIONS: Social inequality in perinatal health outcomes exists in Finland, but seems to have diminished in the 1990s. These data showed that routinely collected birth register data provide a good source for studies on socioeconomic health differences in the perinatal period, but that uncertainty, mainly attributable to the large group of women with difficult to classify socioeconomic status, remains.

Birth Certificates↗

PubMed1994

Genetic linkage mapping for a susceptibility locus to bipolar illness: chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and Xpter.

We are conducting a genome search for a predisposing locus to bipolar (manic-depressive) illness by genotyping 21 moderate-sized pedigrees. We report linkage data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and the pseudoautosomal region at Xpter. To analyze for linkage, two-point marker to illness lod scores were calculated under a dominant model with either 85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance, and two affection status models. Under the dominant high penetrance model the cumulative lod scores in the pedigree series were less than -2 at theta = 0.01 in 134 of 142 loci examined, indicating that if the disease is genetically homogeneous linkage could be excluded in these marker regions. Similar results were obtained using the other genetic models. Heterogeneity analysis was conducted when indicated, but no evidence for linkage was found. In the course of mapping we found a positive total lod score greater than +3 at the D7S78 locus at theta = 0.01 under a dominant, 50% penetrance model. The lod scores for additional markers within the D7S78 region failed to support the initial finding, implying that this was a spurious positive. Analysis with affected pedigree member method for COL1A2 and D7S78 showed no significance for linkage but for PLANH1, at the weighting functions f(p) = 1 and f(p) = 1/sqrt(p) borderline P values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at the mineralocorticoid receptor (MLR) and calmodulin II (CALMII) genes. These genes were genetically mapped and under affection status model 2 and a dominant, high penetrance mode of transmission the lod scores of < -2 at theta = 0.01 were found.

Bipolar Disorder↗

PubMed2002

Sex stratification of an inflammatory bowel disease genome search shows male-specific linkage to the HLA region of chromosome 6.

Inflammatory bowel disease (IBD) is a multifactorial disorder, with both genetic and environmental factors contributing to the two clinical phenotypes of Crohn's disease (CD) and ulcerative colitis (UC). The underlying genetic model is thought to involve multiple genes with complex interactions between disease loci, and the NOD2 gene on chromosome 16 has recently been identified as a CD susceptibility locus. Several genome-wide linkage studies have identified candidate regions, but there has been little replication across studies. Here we investigate the role of sex-specific loci in susceptibility to IBD. Linkage data from our previously reported genome search and follow-up study were stratified by the sex of the affected sib pair. Non-parametric linkage analysis was performed using Genehunter Plus. Simulation studies were used to assess the significance of differences in LOD scores between male and female families for each chromosome. Several regions of sex-specific linkage were identified, including existing and novel candidate loci. The major histocompatibility region on chromosome 6p, referred to as IBD3, showed evidence of male-specific linkage with a maximum LOD score of 5.9 in both CD and UC male-affected families. Regions on chromosomes 11, 14 and 18 showed strong evidence of linkage in male-affected families but not in female-affected families. No evidence of sex-specific linkage was found in the IBD1 or IBD2 candidate regions of chromosomes 16 and 12. The existence of sex-specific linkage is further evidence of the complex mechanisms involved in IBD and will facilitate future studies to identify susceptibility genes.

Chromosome Mapping↗

PubMed1989

Genetic organization of complement receptor-related genes in the mouse.

Using an interspecific cross, gene linkage relationships among members of the murine complement receptor-related genes, C4bp, Cfh, Mcry, and Mcr2, were analyzed by segregation of RFLP in 200 mice. The human homologues of these genes are tightly linked, composing the RCA locus, which maps to human chromosome (Chr.)1q32, within a large linkage group conserved between human Chr.1q21-32 and mouse Chr.1. RFLP associated with C4bp and Cfh map within this conserved linkage group; Cfh is located 9 cM telomeric to C4bp, which is consistent with linkage data for their human homologues. Mcry and Mcr2, while tightly linked, are located outside the conserved group, 40 cM telomeric to C4bp. These data suggest that a translocation or inversion occurred within the RCA family during the evolution of the mouse, defining a breakpoint of this large conserved linkage group.

Animals↗