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At least 379 records · Page 21Linked to original sources
PubMed1998

Mutants and duplication in chromosome 7 (syn. 5H) in the barley line HA21: duplications may enhance QTLs and serve to make constant linear cis-heterozygosity.

Cytological and linkage data indicate a duplication in the short arm of chromosome 7 (syn. 5H) in the mutant line HA21 (barley, Hordeum vulgare, cv. 'Pirkka'). The associated mutant (ha21) shows a weighted average linkage of 22.1 cM with pld, hitherto an ignored anthocyaninless gene, of cv. Pirkka. Some crosses produce F2 segregants with an exaggerated ha21 phenotype which may represent position effect or increased dosage of the mutant gene through recombination. Compared with cv. Pirkka, HA21 has changes in grain chemistry (alpha- and beta-amylase, beta-glucanase), which may be caused by changed QTL dosage or QTL position effect due to duplication. The use of duplication in creating constant +m/+ m or m+/m+ linear cis-heterozygotes is suggested. Linear cis-heterozygotes may produce stable heterosis or attenuate the undesired effects of drastic mutants.

Chromosome Mapping↗
PubMed2005

A novel Markov chain monte carlo approach for constructing accurate meiotic maps.

Mapping markers from linkage data continues to be a task performed in many genetic epidemiological studies. Data collected in a study may be used to refine published map estimates and a study may use markers that do not appear in any published map. Furthermore, inaccuracies in meiotic maps can seriously bias linkage findings. To make best use of the available marker information, multilocus linkage analyses are performed. However, two computational issues greatly limit the number of markers currently mapped jointly; the number of candidate marker orders increases exponentially with marker number and computing exact multilocus likelihoods on general pedigrees is computationally demanding. In this article, a new Markov chain Monte Carlo (MCMC) approach that solves both these computational problems is presented. The MCMC approach allows many markers to be mapped jointly, using data observed on general pedigrees with unobserved individuals. The performance of the new mapping procedure is demonstrated through the analysis of simulated and real data. The MCMC procedure performs extremely well, even when there are millions of candidate orders, and gives results superior to those of CRI-MAP.

Bayes Theorem↗
PubMed1992

Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4.

A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3' untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster.

Amino Acid Sequence↗
PubMed1994

Genetic linkage analysis of familial amyotrophic lateral sclerosis using human chromosome 21 microsatellite DNA markers.

Amyotrophic lateral sclerosis (ALS: Lou Gehrig's Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord. We previously reported linkage of a gene for familial ALS (FALS) to human chromosome 21 using 4 restriction fragment length polymorphism DNA markers [Siddique et al.: N Engl J Med 324:1381-1384, 1991] and identified disease-associated mutations in the superoxide dismutase (SOD)-1 gene in some ALS families [Rosen et al.: Nature 362:59-62, 1993]. We report here the genetic linkage data that led us to examine the SOD-1 gene for mutations. We also report a new microsatellite DNA marker for D21S63, derived from the cosmid PW517 [VanKeuren et al.: Am J Hum Genet 38:793-804, 1986]. Ten microsatellite DNA markers, including the new marker D21S63, were used to reinvestigate linkage of FALS to chromosome 21. Genetic linkage analysis performed with 13 ALS families for these 10 DNA markers confirmed the presence of a FALS gene on chromosome 21. The highest total 2-point LOD score for all families was 4.33, obtained at a distance of 10 cM from the marker D21S223. For 5 ALS families linked to chromosome 21, a peak 2-point LOD score of 5.94 was obtained at the DNA marker D21S223. A multipoint score of 6.50 was obtained with the markers D21S213, D21S223, D21S167, and FALS for 5 chromosome 21-linked ALS families. The haplotypes of these families for the 10 DNA markers revealed recombination events that further refined the location of the FALS gene to a segment of approximately 5 megabases (Mb) between D21S213 and D21S219.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyotrophic Lateral Sclerosis↗
PubMed1995

Modeling interference in genetic recombination.

In analyzing genetic linkage data it is common to assume that the locations of crossovers along a chromosome follow a Poisson process, whereas it has long been known that this assumption does not fit the data. In many organisms it appears that the presence of a crossover inhibits the formation of another nearby, a phenomenon known as "interference." We discuss several point process models for recombination that incorporate position interference but assume no chromatid interference. Using stochastic simulation, we are able to fit the models to a multilocus Drosophila dataset by the method of maximum likelihood. We find that some biologically inspired point process models incorporating one or two additional parameters provide a dramatically better fit to the data than the usual "no-interference" Poisson model.

Animals↗
PubMed1992

Non-specific X linked mental retardation with aphasia exhibiting genetic linkage to chromosomal region Xp11.

A new type of non-specific X linked mental retardation is described in a three generation family. The three affected males had severe mental retardation (IQ 20 to 30), mutism, growth failure, frequent infections, seizures, and the following minor anomalies: brachycephaly, frontal hair whorl, square face, large mouth, thick lips, and prognathism. There was not a characteristic facies. Normal laboratory studies on the proband included a karyotype with fragile X screening, skeletal survey, blood amino acid, urine organic acid, and HGPRT levels. Linkage analysis was performed with 10 X chromosome DNA probes of which probe DXS255 at chromosomal region Xp11.22 gave a maximal two point lod score of 2.10 if phase was inferred and 1.20 if it was not. Crossovers were shown with probes mapping to regions Xp22, Xp21, and Xq28. Comparison of these patients with 80 X linked causes of mental retardation, including 41 which might be classified as 'non-specific', showed no other disorders compatible with the phenotypic and linkage data.

Abnormalities, Multiple↗
PubMed1989

Linkage analysis under "random" and "genetic" reduced penetrance.

We examined whether the results of linkage analysis are affected by the reasons for so-called "reduced penetrance". We simulated linkage data with random reduced penetrance and contrasted that with data that were simulated under inheritance controlled by two loci interacting epistatically. For the two-locus disease models, one of those loci was linked to the marker. All data, irrespective of how the data were simulated, were analyzed under the assumption of a single-locus genetic model with random reduced penetrance. We found that there appears to be little bias in the results of linkage analysis whether the "reduced penetrance" was caused by random (usually interpreted as environmental) factors or by strictly genetic factors. We also illustrate that when the trait or disease is influenced by more than one locus, the inheritance of the trait at the linked locus is the important consideration, not the inheritance of the trait per se.

Computer Simulation↗
PubMed1994

Familial migraine: exclusion of the susceptibility gene from the reported locus of familial hemiplegic migraine on 19p.

Genetic isolates are highly useful in analyses of the molecular background of complex diseases since the enrichment of a limited number of predisposing genes can be predicted in representative families or in specific geographical regions. It has been suggested that the pathophysiology and etiology of familial hemiplegic migraine (FHM) and typical migraine with aura are most probably the same. Recent assignment of FHM locus to chromosome 19p in two French families makes it now possible to test this hypothesis. We report here linkage data on four families with multiple cases of migraine disorder originating from the genetically isolated population of Finland. We were interested to discover whether the migraine in these families would also show linkage to the markers on 19p. We could exclude a region of 50 cM, flanking the reported FHM locus, as a site of migraine locus in our four families. It seems evident that locus heterogeneity exists between different diagnostic classes of migraine spectrum of diseases and also between different ethnic groups.

Chromosome Mapping↗
PubMed1992

Studies on the Mx transposable element system in maize recovered from X-irradiated stocks.

The unstable mutant bz-x3m arose in a plant subjected to X-irradiation. The element at the bronze locus is non-autonomous and recombination data indicate that an autonomous element is tightly linked. The autonomous element has been designated Mx (mobile element induced by X-rays) and the non-autonomous element, rMx (responder to Mx). Linkage data indicate that a second Mx lies near the end of the short arm of chromosome 9; in one plant, an Mx that is unlinked was detected. Distinguishing characteristics of bz-x3m are a large window of time in endosperm development during which somatic reversions can arise and a wide range in the frequency at which they occur; these features are heritable. With increasing doses of bz-x3m and Mx, the window expands and the frequency range increases. In kernels containing the bz-x3m allele and the tightly linked Mx, breakage occurs in chromosome 9 distal to the C locus, resulting in breakage-fusion-bridge patterns for endosperm markers that lie proximal to the break. The frequency of breaks and the developmental time at which they occur exhibit the same dosage effect as the somatic reversions of the bz-x3m allele. These observations suggest that an rMx (designated rMxBr) that causes chromosome breakage is positioned distal to the C locus. At the molecular level, the bz-x3m allele is associated with a 0.5 kb increase in fragment size in DNA samples digested with BglII, EcoRI, HindIII and PstI; in germinal revertants, the fragment size returns to that of the progenitor.

Alleles↗
PubMed1982

Aminolevulinate dehydratase (E.C. 4.2.1.24): linkage analysis.

Linkage data on aminolevulinate dehydratase (ALADH, E.C. 4.2.1.24) and a series of other human genetic markers are presented. One hundred and two families (25 of them being informative) from southwestern Germany were tested. Close linkage (theta = 0.05) between ALADH and the following markers could be excluded: Rh, PGM1, Fy, ACP1, MNSs, HLA, Bf, GLO, PGM3, Jk, Pi, PGP, K, GPT. There is some evidence of possible linkage with HPA.

Electrophoresis, Starch Gel↗
PubMed2004

Hospital chart review provided more accurate comorbidity information than data from a general practitioner survey or an administrative database.

BACKGROUND AND OBJECTIVE: The accuracy of comorbidity data within the Western Australian Data Linkage System was evaluated by means of comparison with hospital charts and a general practitioner (GP) survey. METHODS: Patients (n=2,037) with a hospital admission from 1991 to 1996 were selected. Linked data were extracted for 100 comorbidities, categorized into 16 diagnostic chapters, for each hospital admission within a 5-year period. Clinical chart review and a GP survey were performed. Comorbidity occurrence in each data source and false-positive and false-negative diagnoses were ascertained. RESULTS: Administrative data contained 45.5% of comorbidity recorded in hospital charts and underascertained secondary conditions for all 16 diagnostic chapters. False-positive diagnoses were low for most conditions (range: 0-1.5%); however, a high occurrence of false negatives existed for all comorbidity chapters (range: 16.3-91.3%). GP-identified comorbidity was 20.0% greater than that found using administrative data but, with the exceptions of injury-poisoning and cutaneous-subcutaneous diseases, was less (42.0%) than that observed from hospital charts. CONCLUSION: Our results indicate that when accurate comorbidity data are crucial to health outcome research, hospital chart review (as opposed to using administrative data) may be required. Furthermore, surveying GPs, at least in Australia, appears an unsatisfactory alternative to hospital charts for obtaining retrospective comorbidity information.

Comorbidity↗
PubMed2000

Mapping of the CYP1A1, SSTR1 and TTF1 genes to pig chromosome 7q refines the porcine-human comparative map.

The cytochrome P-450, subfamily I, polypeptide 1 (CYP1A1), somatostatin receptor 1 (SSTR1) and transcription termination factor 1 (TTF1) genes, predicted to reside on SSC7q based on chromosome painting studies, were selected for genetic mapping in the pig. Porcine sequence tagged sites (STSs) spanning 0.9-1.5 kb genomic DNA sequences were generated and all genes were physically assigned to SSC7q12-q23, q26 using a pig-rodent somatic cell hybrid panel. Direct sequencing of PCR products from four different breeds revealed single nucleotide polymorphisms (SNPs) in all genes. SNPs in the SSTR1 and CYP1A1 genes allowed simple genotyping using PCR-restriction fragment length polymorphism (RFLP) analysis and linkage mapping with the PiGMaP reference families. SSTR1 was found to be closely linked to CYP1A1 (0.0 cM; LOD = 11.1) and ANPEP (0.0 cM; LOD = 9.0). This refined the localization of a previously identified breakpoint in the linkage map between regions with orthology to human chromosome 15q (represented by CYP1A1 and ANPEP) and 14q (represented by SSTR1). Moreover, multipoint linkage data suggest inverted segments of orthology between HSA14q11-q13 and SSC7q. The TTF1 SNP was confirmed by allele-specific PCR but was not informative in any of the families used for linkage analysis.

Animals↗
PubMed1981

Polymorphism of human c5.

C5 is polymorphic in Melanesians and related peoples. The polymorphism is demonstrated by isoelectric focusing and functional detection. Inheritance is autosomal and codominant. Preliminary linkage data suggest that C5 is not close to HLA.

Complement C5↗
PubMed1994

Linkage analysis in two schizophrenic families originating from a restricted subpopulation of Finland.

We report here linkage data on two families with multiple cases of schizophrenia originating from the genetically isolated population of Finland. We analyzed chromosomal DNA regions containing relevant candidate genes for schizophrenia and chromosomal regions which have been among the most widely studied in schizophrenia research due to associations between chromosomal anomalies and schizophrenia observed in certain families or populations. These include the chromosomal regions 5q11-q13, 11q and 15q21 as well as gene loci coding for components of dopamine, serotonin and amino acid transmitter pathways. No evidence for linkage to any of the chromosomal regions or candidate genes could be obtained, our data in fact suggested exclusion of all these regions as the site for major predisposing loci for schizophrenia in our families. On the 11p region the lod scores obtained deviated in the two families, but the difference remained statistically insignificant. The data emphasize the importance of analyzing families even with restricted genetic background separately since locus heterogeneity is likely to be detected not only between ethnic groups but also between diagnostic classes of the schizophrenia spectrum of diseases.

Adolescent↗
PubMed2006

Characteristics of general practitioner consultations prior to suicide: a nested case-control study in New Zealand.

AIM: To examine characteristics of general practice consultations in a New Zealand primary care population of patients who died by suicide. METHODS: Case control study design, with data linkage between the RNZCGP Research Unit Database, the National Mortality Database and the Hospital Separation Diagnosis Database (hospital discharges) from 1996 to 2001. The cases were suicides who had attended a general practice contributing data to the Research Unit database. Each case was matched by gender and age to three randomly selected patients from the Research Unit database. RESULTS: There were 221 cases of suicide identified, of which 60% had a general practice consultation in the 6 months prior to death. The significant exposure variables, corrected OR (95% CI) in the multivariate analysis were: any previous hospital admission (between January 1996 and date of death) for a psychiatric condition, 23.75 (9.01 to 62.63); any notation in the general practice record of depression, suicidal ideation or self-harm, 14.97 (4.61 to 48.65); previous hospital admission with self-harm, 8.39 (1.73 to 40.65); and general practice prescription of sedatives, 4.34 (1.69 to 11.10). CONCLUSIONS: In general, general practice patients who commit suicide have higher rates of depression, suicidal ideation, previous self harm, and sedative prescription than average.

Adolescent↗
PubMed1996

Genetic recombinational and physical linkage analyses on slash pine.

Slash pine is native to the southeastern USA, but is commercially valuable world-wide as a timber-, fiber- and resin-producing species. Breeding objectives emphasize selection for fusiform rust disease resistance. Identification of markers linked to genetic factors conditioning specificity should expand our knowledge of disease development. Towards this end, random amplified polymorphic DNA (RAPD) markers were identified and mapped in a tree hypothesized to be homozygous dominant for resistance at one locus and homozygous recessive at another. Because the DNA prepared for analysis was from haploid maternally-inherited, megagametophyte tissue of seeds, RAPD markers were observed as either present or absent. The analysis revealed 13 linkage groups of three or more loci, ranging in size from 28 to 68 cM, and nine linked pairs. The 22 groups and pairs included 73 RAPD markers and covered a genetic map distance of approximately 782 cM. Genome size estimates, based on linkage data, range from 2,880 to 3,360 cM, and equal 6.0-6.9 x 10(6) bp/cM (physical size > 20,000 Mbp). Using a 30 cM map scale and including unlinked markers, ends of linkage groups, and linked pairs, the RAPD markers account for approximately 2,160 cM or 64-75% of the genome. Mapping 80 additional RAPD markers placed 131 loci total in 20 linkage groups of three or more loci, nearly doubling the coverage in the groups to a genetic map distance of approximately 1,347 cM. Two other slash pine trees also have been RAPD mapped. DNA-DNA in situ hybridization and cytochemical staining are being used to integrate the genetic recombinational maps. A karyotype and ideogram have been prepared for slash pine (2n = 2x = 24); metaphase chromosome preparations show 11 pairs of long metacentric chromosomes and one shorter pair of submetacentric chromosomes. Patterns of fluorescence in situ hybridization to genes for the large and small rRNA subunits and fluorochrome banding patterns using the GC-base-specific chromomycin A3 (CMA) and AT-base-specific 4',6-diamidino-2-phenylindole (DAPI) allowed all twelve pairs of chromosomes to be identified and a standard karyotype established. A family of sequences associated with (TTTAGGG)n related repeats has been identified in slash pine using a labeled synthetic oligonucleotide probe. Fluorescence in situ hybridization shows a weak signal at telomeres and significantly stronger intensity at non-telomeric sites. The most common non-telomeric location was in the pericentric regions of chromosomes; interstitial sites of hybridization were relatively common. Microsatellite DNAs, an abundant retrotransposon-like element, and total genomic in situ hybridization and species and chromosome specific DNAs are being evaluated for analyses of interspecific hybrids and chromosome evolution between related species. Interest in low and single copy sequences is increasing.

Breeding↗
PubMed2004

Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis.

The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P=0.00043; Pc=0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P=0.0036; Pc=0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P=0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P=0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA.

Aged↗
PubMed1993

Allelic association and linkage studies in Wilson disease.

We have studied 21 families with Wilson disease (WND), using restriction fragment length polymorphisms (RFLPs) in the 13q14.3 region, to measure linkage of these markers to the disease locus. In addition to previously described markers, we include linkage data for a newly isolated marker (D13S86) and an established marker (D13S56), which were previously not placed on the genetic map in the region of the WND locus. Our data, including those from two recombinant families, support the location of WND between the markers D13S31 and D13S59. We have examined the distribution of marker alleles at the loci studied and have found that D13S31 and D13S228, and associated microsatellite marker, show a non-random distribution on chromosomes carrying the WND mutation. The significant linkage disequilibrium indicates that these two markers must be close to the WND locus.

Alleles↗