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J Daniels

Publications and source records attributed to J Daniels.

At least 19 recordsLinked to original sources
PubMed1998

A simple method for analyzing microsatellite allele image patterns generated from DNA pools and its application to allelic association studies.

Allelic association studies provide the most powerful method for locating genes of small effect contributing to complex diseases and traits. However, in outbred populations, allelic association is usually maintained only over distances of <=1 cM. Therefore, systematic searches over large regions are costly. Here we present a method involving DNA pooling that can be used as a rapid preliminary screen for allelic association with the most common class of polymorphic markers, single-sequence repeats. Patient and control samples are pooled separately, and markers are typed in the two pools. By use of primers with fluorescent 5' ends, PCR products can be analyzed on an automated sequencing apparatus. Allele image patterns (AIPs) produced for the two groups are overlaid and differences in pattern area between pools computed. From this, a DeltaAIP statistic is calculated from the difference in areas between the two AIPs expressed as a fraction of the total shared and nonshared area. AIPs of a range of different-sized pools were generated by computer simulation for markers with a range of allele sizes and frequencies. DeltaAIPs from pools and chi2 values for individual genotypings were compared, with both simulated and real data from microsatellite markers. The results demonstrated a high correlation between DeltaAIP and chi2 values. DeltaAIP analysis of real microsatellite data indicated the feasibility of using this method in systematic searches for allelic association and generated a small number of false positives but few false negatives. We conclude that DeltaAIP analysis of DNA pools can be used effectively and efficiently as a rapid screen for allelic association in case-control studies.

Alleles↗
PubMed1998

Molecular genetic studies of cognitive ability.

Given that the evidence of a substantial genetic contribution to cognitive ability is now convincing, the next challenge is to locate and identify the genes involved. It is likely that there are several genes, each of only small effect. Detection of such so-called quantitative trait loci contributing to polygenic traits in plants and animals is facilitated by the ability to carry out experimental crosses. However, in humans detection of quantitative trait loci depends on studies of siblings or other relative pairs or on allelic association studies aimed at detecting linkage disequilibrium in populations. The allelic association approach is currently being applied to investigate cognitive ability by using both candidate genes and DNA pooling methods that potentially allow rapid screening of the whole genome for quantitative trait loci.

Animals↗
PubMed1998

A prospective study of matrix metalloproteinases in proliferative vitreoretinopathy.

PURPOSE: The migration, proliferation, differentiation, and adhesion of cells and other cellular functions are influenced by the surrounding extracellular matrix, in normal and wound-healing conditions. The matrix metalloproteinases (MMPs) are a family of enzymes that degrade and remodel the extracellular matrix and, thus, play a central role in the wound-healing process. Proliferative vitreoretinopathy (PVR), a wound-healing process in the retina, is a major cause of the failure of retinal detachment surgery. The role of MMPs in the pathobiology of PVR is unknown. We have investigated the presence of MMPs in the vitreous of patients with retinal detachment and the predictive value of MMPs for the future development of PVR. METHODS: A prospective study was conducted on 140 consecutive patients with a rhegmatogenous retinal detachment in whom vitrectomy was considered necessary because of a giant retinal tear and the presence of preoperative PVR, among other reasons. Vitreous samples were obtained and analyzed by zymography for the presence of MMPs. The patients were then followed up for the development of postoperative PVR (mild and severe). RESULTS: Two species of MMPs were detected in the vitreous: MMP-2 and MMP-9. MMP-2 was detected in all of the vitreous samples obtained, whereas MMP-9 was found in only 64 (47%) of 136 samples. The levels of MMPs detected were not significantly associated with the presence of preoperative PVR (P > 0.05), but they were significantly associated (P < 0.05) with the development of postoperative PVR (mild and severe). CONCLUSIONS: The results from this prospective study suggest that MMPs may be an important predictor and may also play a role in the development of postoperative PVR.

Adolescent↗
PubMed1997

No association between general cognitive ability and the A1 allele of the D2 dopamine receptor gene.

Berman and Noble (1995) reported significantly reduced visuospatial performance in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene. Given that visuospatial performance loads highly on an unrotated principal component indexing general cognitive ability, we tested the association between DRD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in the IQ Quantitative Trait Loci (QTL) Project. No statistically significant association between the TAQI A DRD2 alleles and IQ was found. Given that a statistically significant portion of genetic variance for specific cognitive abilities is independent of general cognitive ability, it is possible that the TAQI DRD2 association is specific to visuospatial performance and independent of general cognitive ability.

Adolescent↗
PubMed1997

Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease.

To determine the effect of the ACE gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and the angiotensin 1 receptor gene A1166C polymorphism on the age of onset of end-stage renal failure (ESRF) in PKD1 adult autosomal-dominant polycystic kidney disease (ADPKD), 189 individuals from 46 families with PKD1 were genotyped for each polymorphism. Of the 189 patients 52 (28%) reached ESRF at an average age of 48 +/- 1 year. In patients genotyped for the ACE gene insertion/deletion polymorphism the frequencies of the DD, ID and II genotypes were similar to those expected from Hardy Weinberg equilibrium. In patients with ESRF there was an excess of patients homozygous for the deletion allele (DD: 48% chi2 = 9.97 (1df) P = 0.002). Cumulative renal survival was significantly reduced among those with DD genotype compared to ID and II genotypes. The estimated mean renal survival (95% confidence intervals) were: DD, 52 years [48, 57]; II, 59 years [54, 63]; ID, 64 years [56, 72]; chi2 = 6.13 (1df) P = 0.013, DD versus ID/II. The mean age of renal failure was significantly younger in the DD genotype compared to ID and II genotypes (DD, ID, and II: 44 +/- 2, 49 +/- 2 and 54 +/- 3 years, respectively; P < 0.05 DD vs. ID, P < 0.05 DD vs. II). Ten of the eleven patients who reached ESRF before the age of 40 were homozygous for the deletion allele. The relative risk for ESRF below the age 40 for DD genotype was 17. For all ages there was an overall increased risk of 1.4 for ESRF with the DD genotype. There was no interaction between age of onset of ESRF and either the angiotensinogen M235T allele or angiotensin 1 receptor A1166C polymorphism. This study strongly suggests that PKD 1 patients homozygous for the deletion allele of the ACE gene are at increased risk of developing ESRF at a early age.

Adult↗
PubMed1997

Alcohol screening and brief intervention: where research meets practice.

Numerous studies have consistently shown that quick screening instruments can identify people whose drinking is likely to present health risks and that low-cost, brief interventions are effective in reducing drinking among many such at-risk drinkers. This article describes the results of a one-year policy analysis that explored how alcohol screening and brief intervention (SBI) can be moved to widespread clinical applications in the United States. It introduces the concept of risky drinking and considers the potential of this new technology to reduce it. The research evidence behind this approach is reviewed, and a description of current programs in this and other countries beginning to apply SBI is provided. Economic issues attendant to applications are identified and discussed. The potential for applications in health care is analyzed and summary conclusions from market research are set forth. Recommendations are offered for immediate action.

Alcoholism↗
PubMed1996

Liver hemorrhage during laparotomy in patients with necrotizing enterocolitis.

UNLABELLED: Major liver hemorrhage (LH) without obvious iatrogenic injury was recently observed in several patients during operation for necrotizing enterocolitis (NEC). The purpose of this study was to determine the incidence and risk factors associated with the development of LH in patients with NEC. METHODS: The hospital charts of patients with NEC who underwent surgical exploration during a 5-year period (1989-1994) were reviewed. The patients in whom LH developed without obvious significant iatrogenic liver injury were compared with those who did not have LH. RESULTS: Eight of the 68 patients reviewed had LH. The survival rate for those with LH was 13%, compared with 88% for those without LH (P < .001). The patients with LH had a younger gestational age (28 +/- 3 weeks v 32 +/- 5 weeks) and a lower birth weight (1,262 +/- 489 g v 1,649 +/- 666 g); however, the differences were not significant. The patients with LH had significantly lower preoperative mean arterial blood pressure (35 +/- 1 mm Hg v 46 +/- 3 mm Hg; P < .001) and required greater fluid intake (272 +/- 28 mL/kg/d v 186 +/- 9 mL/kg/d; P < .01) for the 24 hours preceding surgery. CONCLUSION: LH is as an important and lethal complication associated with laparotomy in very small infants with NEC. The presence of hypotension and the administration of large amounts of volume in the preoperative period appear to be risk factors. Earlier surgical intervention and restoration of blood pressure using inotropic agents, once a particular level of fluid administration has been achieved, my be preventive.

Birth Weight↗
PubMed1996

Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the Darier's disease (DAR) region of chromosome 12q23-q24.1.

We have previously described a pedigree in which affective disorder and Darier's disease cosegregate and, in an independent sample of 45 bipolar pedigrees, reported evidence in support of linkage between a putative susceptibility locus for bipolar disorder and markers in the Darier's disease region of chromosome 12q23-q24.1. The maximum evidence for linkage was given by a polymorphism at the gene encoding secretory phospholipase A2 (PLA2A), a candidate gene for affective disorder. Dawson et al. (Psychiatric Genetics, 5, 177-180) recently reported allelic association with the same polymorphism at PLA2A in a sample of 54 bipolar probands and 56 controls. We have been unable to replicate the association in 127 Caucasian British DSMIII-R bipolar probands and 223 Caucasian British controls. However, on the basis of several lines of evidence discussed in the paper, we believe that this genomic region in general, and the PLA2A gene in particular, are worthy of further study as candidates in the search for susceptibility genes for the functional psychoses.

Alleles↗
PubMed1996

Facilitating the recovery of open heart surgery patients through quality improvement efforts and CareMAP implementation.

OBJECTIVE: To illustrate, using a literature review and CareMAPs, how care coordination and implementation of standard protocols can impact clinical outcomes for open heart surgery patients. METHODS: A CareMAP for open heart surgery patients was developed by a multidisciplinary team. To evaluate the effectiveness of CareMAP implementation and specific quality improvement efforts, a pilot study was done that focused on increasing activity levels, decreasing ventilator time, and decreasing the frequency of arterial blood gas sampling for a sample of 55 open heart surgery patients. A rapid recovery program was developed based on the results of this pilot study. A multidisciplinary continuous quality improvement team was developed to focus on three primary areas: ventilator weaning time, activity regimens, and early transfer to the open heart surgery step-down unit. Forty-nine open heart surgery patients were included in the initial program evaluation. RESULTS: The frequency of arterial blood gas sampling decreased from an average of 5.8 per patient to an average of 3.9 per patient. Postoperative length of stay also decreased by 1.3 days for diagnosis related group 106 patients, and 3.7 days for diagnosis related group 107 patients. Results of the pilot study demonstrated additional opportunities for improving the care of open heart surgery patients. Using the rapid recovery program, the average ventilator time decreased by 4.4 hours per patient. The average postoperative length of stay decreased to 4.7 days. CONCLUSIONS: Through the quality improvement process and through the use of CareMAPs and specific protocols, the recovery of open heart surgery patients was facilitated.

Analysis of Variance↗
PubMed1996

Increasing the efficiency of genomic searches for linkage in complex disorders by DNA pooling of affected sib-pairs.

Detection of linkage using a systematic genome scan in nuclear families including an affected sibling pair is an important initial step on the path to cloning susceptibility genes for complex genetic disorders such as bipolar disorder and schizophrenia. We describe a novel method in which the pooled genotype of each affected sib-pair is determined and used in the screening stage of a two-stage genome scan. This method, which involves a single PCR reaction per sib-pair in the screening stage can reduce the required number of genotypings to less than 20% of those required in a conventional single stage procedure whilst maintaining a similar power and probability of type I error.

Bipolar Disorder↗
PubMed1995

No evidence for allelic association between bipolar disorder and monoamine oxidase A gene polymorphisms.

We have tested the hypothesis that DNA markers in the MAOA gene show allelic association with bipolar affective disorder. Eighty-four unrelated Caucasian patients with DSM III-R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8. No evidence for allelic association was observed between any of the markers and bipolar disorder.

Adult↗
PubMed1995

Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23-24.1.

We have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23-q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independent researchers should examine markers from this region in further samples of bipolar pedigrees.

Alleles↗
PubMed1995

No association between schizophrenia and polymorphisms within the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT).

It has been suggested that the cytochrome P450 mono-oxygenase, debrisoquine 4-hydroxylase, is involved in the catabolism and processing of neurotransmitters subsequent to their reuptake into target cells. It is also thought to be related to the dopamine transporter that acts to take released dopamine back up into presynaptic terminals. The present study used the association approach to test the hypothesis that mutations in the genes for debrisoquine 4-hydroxylase (CYP2D6) and the dopamine transporter (DAT) confer susceptibility to schizophrenia. There were no differences in allele or genotype frequencies between patients and controls in the mutations causing the poor metaboliser phenotype in CYP2D6. In addition there was no association found between schizophrenia and a 48bp repeat within the 3' untranslated region of DAT.

Adolescent↗
PubMed1995

Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23.

Protoporphyrinogen oxidase (PPO) catalyses the conversion of protoporphyrinogen IX to protoporphyrin IX. Variegate porophyria (VP), a low-penetrant, autosomal dominate disorder characterized clinically by skin lesions and neurovisceral attacks, is caused by partial deficiency of this enzyme. Linkage between VP and the alpha-1-antitrypsin gene on chromosome 14 has been reported in VP families from South Africa, where the condition occurs at high frequency due to a founder effect. We have cloned a 4.5 kb genomic DNA fragment containing the entire coding sequence for human PPO. This clone has been used to localize the human PPO gene to chromosome 1q23 by fluorescence in situ hybridization analysis. The VP gene was mapped by linkage analysis, using microsatellite markers spanning the region 1q21-q25.1, in seven British VP families. Multipoint analysis between VP, SPTA1, APOA2 and D1S194 gave the maximum LOD score of 6.62 at APOA2, which has been physically mapped to 1q21-q23. Evidence for significant linkage between VP and markers in the alpha-1-antitrypsin region of chromosome 14 was not obtained. Our results assign the genes for PPO and VP to the same region chromosome 1, indicate that the PPO and VP loci are likely to be the same, and provide evidence against locus heterogeneity in VP.

Adolescent↗
PubMed1994

Repeat length variation in the dopamine D4 receptor gene shows no evidence of association with schizophrenia.

The D4 receptor has been shown to exist in several allelic forms (Van Tol et al., Nature 358:149-152, 1992) reflecting variation in the number of 48 base-pair sequence repeats in the putative cytoplasmic loop. We report a comparison of repeat length variation between schizophrenic patients and controls. Our sample of 106 unrelated schizophrenic cases and 119 controls showed no significant differences in allele or genotype distribution between patients and controls. In particular, we were unable to support the previous observation of an excess of 4-repeat homozygotes in patients.

Alleles↗
PubMed1994

Variation at the fragile X locus does not influence susceptibility to bipolar disorder.

Over the last 20 years several pedigrees have been reported which are suggestive of linkage between susceptibility to bipolar disorder and markers on chromosome Xq28. Other workers have failed to replicate these reports and the methodology of the positive reports has been criticised. Recently there have been several reports of an association between fragile X (FRA(X)) and affective disorder within families and in unrelated individuals compared with controls. Such reports could be consistent with the Xq28 marker reports because FRA(X) maps to Xq27.3. We report a study at the FRA(X) CGG repeat locus in 79 unrelated Caucasian bipolar probands without fragile X syndrome and 77 unrelated controls. We found no evidence that variation at this locus confers susceptibility to bipolar disorder.

Adult↗