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P W Lane

Publications and source records attributed to P W Lane.

At least 19 recordsLinked to original sources
PubMed2003

Multifactorial screening design and analysis of SELDI-TOF ProteinChip array optimization experiments.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry is a powerful tool for rapidly generating protein expression data (peptide and protein profiles) from a large number of samples. However, as with any technology, it must be optimized and reproducible for one to have confidence in the results. Using a classical statistical method called the fractional factorial design of experiments, we assessed the effects of 11 different experimental factors. We also developed several metrics that reflect trace quality and reproducibility. These were used to measure the effect of each individual factor, and the interactions between factors, to determine optimal factor settings and thus ultimately produce the best possible traces. Significant improvements to output traces were seen by simultaneously altering several parameters, either in the sample preparation procedure or during the matrix preparation and application procedure. This has led to the implementation of an improved method that gives a better quality, reproducible, and robust output.

Animals↗
PubMed2001

Maximization of signal derived from cDNA microarrays.

Microarray technology is a powerful tool for generating expression data on a large number of genes simultaneously. However, as for any assay, it must be reproducible to give confidence in the results. Using a classical statistical method--the factorial design of experiments--we have assessed the effects of different experimental factors in our system. Significant effects on signal were seen when the standard components were substituted with a different enzyme, fluorescent label, or RNA purification method. This has led to the implementation of an improved procedure that maximizes signal without affecting the variability of the system, thus increasing the signal-to-noise ratio. In addition, we were able to quantify the variability between microarrays and replicates within microarrays.

Analysis of Variance↗
PubMed1998

Patchy fur, a mouse coat mutation associated with X-Y nondisjunction, maps to the pseudoautosomal boundary region.

Patchy fur is a semidominant X-linked mutation in the mouse, resulting in a sparse coat. The Paf mutation also alters the normal segregation of the X and the Y chromosomes during male meiosis by causing nondisjunction at anaphase I. Analysis of 1139 female meioses from an intersubspecific backcross using 15 PCR-based markers localizes Paf to an approximately 0.2-cM interval that includes the pseudoautosomal boundary. The meiotic nondisjunction phenotype may result from a chromosomal rearrangement that includes pseudoautosomal sequences and affects XY pairing.

Animals↗
PubMed1998

Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9.

The neuronal ceroid lipofuscinoses (NCLs) comprise a set of at least 6 distinct human and an unknown number of animal diseases characterized by storage of proteolipids in lysosomes of many cell types. By unknown mechanisms, this accumulation leads to or is associated with severe neuronal and retinal degeneration. The genes for 3 human NCLs, infantile, late infantile, and juvenile, have been cloned. The first murine form of NCL, the motor neuron degeneration (mnd) mouse, has been described and mapped to proximal Chromosome 8. Here we describe a second genetic variant of NCL in the mouse, neuronal ceroid lipofuscinosis, nclf. These mice exhibited a phenotype that was almost exactly the same as that observed in mnd/mnd mice. Homozygous nclf mice developed progressive retinal atrophy early in life and become paralyzed at around 9 months of age. They accumulated luxol fast blue staining material in cytoplasm of neurons and many other cell types. Ultrastructurally, affected lysosomes had a "finger print pattern" with membranous material arranged in "pentalaminar" patterns. Affected mice developed severe cerebral gliosis in late stages of their disease. They also had severe Wallerian degeneration of long tracts in spinal cord and brain stem, lesions that accounted for the distinctive upper motor neuron signs displayed by both nclf/nclf and mnd/mnd mice. By crossing nclf/nclf mice with CAST/Ei mice, linkage analysis of nclf with respect to SSLP markers was performed, showing that nclf is located on Chromosome 9 between D9Mit164 and D9Mit165, in a region that is homologous with human Ch 15q21, where the gene for one variant of late infantile NCL, CLN6, recently has been mapped. The genes for two proteolipids known to be stored in lysosomes of animals and people with NCL were also mapped in this study and found not to map to the mnd or nclf loci nor to any mouse locus homologous to any known human NCL disease locus.

Animals↗
PubMed1995

Mapping the mouse dactylaplasia mutation, Dac, and a gene that controls its expression, mdac.

Dactylaplasia is an inherited mouse limb malformation whose manifestation is clearly dependent on the interaction of two genes and thus represents an excellent model system for studying such gene interactions in vivo. The Dac mutation is inherited as a semidominant trait and may be a model for some forms of human ectrodactyly. Heterozygotes show absence of digits on each foot; the long bones are normal. On the SM/Ckc background on which the mutation occurred, Dac homozygotes die around birth. We mapped Dac to the distal end of Chr 19 by backcross segregation analysis A closely linked marker was then used to distinguish +/+, Dac/+, and Dac/Dac genotypes of embryos and adults. When intercrossed with the NZB/BINJ strain, Dac homozygotes were shown to be viable and fertile, but had a more severe limb malformation (only a single remaining digit) than heterozygotes. Expression of the abnormal limb phenotypes of Dac/+ and Dac/Dac mice also depends on homozygosity for a recessive allele of another unlinked gene, mdac, that is polymorphic among inbred mouse strains. We mapped mdac to the middle of Chr 13 by segregation analysis of both recombinant inbred strains and backcross progeny.

Animals↗
PubMed1993

Urogenital syndrome (us): a developmental mutation on chromosome 2 of the mouse.

Urogenital syndrome (us) is a recessive mutation in mice characterized primarily by abnormalities of the axial skeleton and urogenital organs. We established linkage of us with the centromeric end of Chromosome (Chr) 2, using the Robertsonian Chr Rb(2.8)2Lub. Analysis of progeny from crosses using the Chr 2 markers Danforth's short tail (Sd) and ulnaless (Ul) positioned us near two loci that have recently been mapped by RFLPs, nonerythroid alpha-spectrin (Spna-2) and the paired-box-containing-gene-8 (Pax-8). The position of us relative to these loci was established by analysis of progeny from interspecific backcrosses between the us strains and Mus spretus. The estimated map distances and most likely gene order are centromere-Pax-8-2.1 +/- 1.2-us-0.7 +/- 0.7-Spna-2; however, the reverse order cannot be ruled out. Our data make it unlikely that us is a mutation in either Spna-2 or Pax-8. Spna-2 is close enough to us, however, to be a useful marker for positional cloning of the us gene. The human mutation Nail-patella-syndrome (NPS1) maps to the region of human Chr 9 (9q34) that is homologous to the us region of mouse Chr 2. Phenotypic similarities between the two syndromes suggest the possibility that they are caused by mutations at homologous loci.

Animals↗
PubMed1992

Spontaneous renal artery thrombosis associated with altered mental status.

Renal artery thrombosis is much less common than renal artery occlusion by emboli. When it does occur, it is usually a result of blunt abdominal trauma or a thrombus superimposed on an atherosclerotic plaque. Numerous other factors have been associated with renal artery thrombosis. Spontaneous renal artery thrombosis is a rare phenomenon in itself. This case represents spontaneous renal artery thrombosis associated with an altered mental status. Clinical features with suspected etiologies are reviewed. Recommendations for future evaluations are given.

Adult↗
PubMed1991

Hairpatches, a single gene mutation characterized by progressive renal disease and alopecia in the mouse. A potential model for a newly described heritable human disorder.

A new murine mutation, hairpatches (Hpt), is on chromosome 4, 18.1 recombination units distal to brown near the interferon alpha and beta chain structural gene complex. On the inbred HPT/Le strain background, Hpt is semi-dominant, and Hpt/Hpt mice die in utero by 6 to 8 days of gestation. Such death in utero is associated with abnormalities of embryonic ectodermal derivatives. However on the (C57BL/6J x C3HeB/FeJ-a/a) segregating hybrid background, Hpt is a fully dominant mutation. HPT/Le Hpt/+ mice can be recognized by 3 to 4 days of age by patches of lightly pigmented skin. These mice show reduced numbers of hair follicles, abnormalities in hair follicle structure, and patchy absence of hair throughout life. By 2 weeks of age, abnormal hair follicle development is accompanied by thickening of the epidermis, reduction in levels of subcutaneous fat, and dermal inflammation. Progressive glomerulosclerosis, resulting in chronic kidney failure, is accompanied by increases in glomerular mesangial matrix, deposition of immune complexes, and glomerular enlargement. Scanning electron microscopic studies revealed abnormalities of podocytes including disorganization, swelling, and fusion of the foot processes. Increase in serum blood urea nitrogen levels accompanies conspicuous renal histopathologic changes. Cardiovascular changes in Hpt/+ mice are evidenced by hypertrophy of the left heart ventricle. Increased systolic blood pressure in these animals was found by 3 months of age. Anemia occurs in Hpt/+ mice by 40 weeks. The Hpt/+ mutation provides a valuable new animal model for chronic kidney disease accompanied by skin abnormalities and ventricular hypertrophy. The pathologic changes caused by this mutation are similar to those reported in affected family members with a newly described autosomal dominant human disease.

Alopecia↗
PubMed1990

Hydrocephalus with hop gait (hyh): a new mutation on chromosome 7 in the mouse.

Hydrocephalus with hop gait (hyh) is a new lethal recessive mouse mutation that arose in the C57BL/10J strain at The Jackson Laboratory. It has been mapped to the proximal end of Chromosome 7 close to the Gpi-1 locus. This homozygous mutant is characterized clinically by a domed head and a hopping gait observable at 2 weeks of age and death between 4 and 10 weeks of age. The affected mice have dilated lateral ventricles and a large third ventricular cyst, patent through narrowed rostral cerebral aqueduct, cystic caudal aqueduct and no communication of the aqueduct with the fourth ventricle. The cerebellum has a mild cortical malformation.

Animals↗
PubMed1989

An explanation for the apparent losses of metals in a long-term field experiment with sewage sludge.

Large losses of metals applied to soil in metal-contaminated sewage sludge have been reported. The potential pathways of loss, including lateral movement from treated plot areas, have not been examined. A field experiment, which started in 1942, was investigated to determine the amount of lateral movement of zinc, cadmium, copper, nickel, chromium and lead due to conventional cultivation processes. A two-dimensional 'dispersion' model (i.e. movement of soil due to cultivation) fitted well to the observed movement of metals, and gave coefficients for movement of 0.24 and 0.13 m(2) per tillage operation in dimensions parallel or perpendicular to the direction of ploughing, respectively. For testing purposes, the model was used to predict the concentrations of metals in specific areas of a plot or average concentrations for whole plots at different points in time. The concentrations measured in soil samples agreed well with the predicted values. Finally, the model was also used to estimate the proportion of the metal load applied between 1942 and 1961 that remained in the 0-27 cm cultivated layer in 1985. About 80% was accounted for: this large recovery is of great relevance to the long-term disposal of metal-contaminated wastes to land. Detailed analyses of soil profile samples showed that approximately 1% of the metals applied had moved 3.5 cm below the plough layer or less, but there was no evidence of accumulation of metals in deeper horizons down to 46 cm. These results are discussed in relation to the other potential losses of metals in the experiment.

Journal Article↗
PubMed1988

New mutation causing sterility in the mouse.

A new murine mutation, skeletal fusions with sterility, sks, has been identified. This mutation causes arrest during the pachytene stage of virtually all spermatogenic cells. Defects in chromosome pairing and appearance of the synaptonemal complex during meiosis in the male are apparent, but defective pairing is probably not the cause of sterility. Affected females are functionally infertile. Oocytes are capable of undergoing meiotic maturation in vitro but cannot be fertilized in vitro. Affected individuals of both sexes are characterized by fusions of vertebrae and of ribs. The sks gene has been mapped to Chromosome 4, 16.6 cM distal to the brown locus.

Animals↗
PubMed1982

Vibrator (vb): a spinocerebellar system degeneration with autosomal recessive inheritance in mice.

Vibrator (gene symbol vb), an autosomal recessive mutation, occurred spontaneously in the DBA/2J strain of mice, was rescued by a single cross to C57BL/6J and subsequent brother X sister mating, and has been mapped near shaker-2 (sh-2) and vestigial tail (vt) on chromosome 11. The name emphasizes the unusually rapid (18-20 Hz) postural action tremor expressed in juvenile homozygotes. Selected neurons in spinal cord, and later in brainstem and cerebellum, show progressive degenerative changes featuring dilated cisternae of endoplasmic reticulum in cell bodies, dendrites and axons, with eventual severe intracellular vacuolation and some cell death.

Animals↗
PubMed1982

Analysis of covariance and standardization as instances of prediction.

In this paper, prediction provides the basis for unifying the procedures of covariances adjustment and standardization. Analysis of covariance is a method of forming predictions from a linear model; it is used when qualitative effects are to be studied and the effects of continuous variables are to be adjusted for. An essential feature is the division into effects of interest and effects for which adjustment is required. Covariates may also be qualitative: as such, they are used implicitly in experimental designs with blocks, where treatment effects are adjusted for the effect of blocks. The technique of standardization is well-known in epidemiology and demography as a method of adjusting explicitly for qualitative effects. The same division of effects applies when an analysis that uses generalized linear models is summarized. Two distinct types of prediction, which give identical results in classical linear models, are available: prediction may be conditional on a fixed value of a covariate, or marginal on a distribution of values such as the distribution in the set of data being analysed. Prediction methods are illustrated by the analysis of a table of proportions by use of a logit model.

Adult↗
PubMed1972

Susceptibility to spontaneous pneumonitis in an inbred strain of beige and satin mice.

Among mice of strain SB/Le, homozygous for the mutant genes beige (bg), satin (sa), and white-bellied agouti (A(w)), 70% developed progressive pneumonitis by 6 months of age. Among backcross offspring from an outcross to C57BL/6J-A(w-J), 49% of homozygous beige and 11% of nonbeige genotypes developed pneumonitis by 6 months of age. The evidence indicates that a specific action of the beige gene increases susceptibility to progressive pneumonitis. Lymphadenopathy, including reticulum cell neoplasms and atypical lymphoproliferative lesions, was observed in high incidence in sa+/sa bg males, suggesting a closer association with satin than with beige. Beige mice show giant lysosomal granules in the leukocytes and pigment dilution closely analogous to the Chediak-Higashi syndrome in man and similar disorders in mink and cattle. Strain SB/Le provides a convenient model in a laboratory animal for study of the increased susceptibility to infection analogous to that of the Chediak-Higashi syndrome.

Age Factors↗