Into the post-HapMap era (2008)
The HapMap Project has shifted genetic epidemiology of complex inheritance away from linkage into association mapping of genes affecting disease and response to therapy. Starting with a physical map...
Ennis, S., Murray, A., Brightwell, G., Morton, N.E., Jacobs, P.A.
In its expanded form, the fragile X triplet repeat at Xq27.3 gives rise to the most common form of inherited mental retardation, fragile X syndrome. This high population frequency persists despite...
Ennis, S., Murray, A., Brightwell, G., Morton, N.E., Jacobs, P.A.
In its expanded form, the fragile X triplet repeat at Xq27.3 gives rise to the most common form of inherited mental retardation, fragile X syndrome. This high population frequency persists despite...
A history of association mapping (2007)
The current exciting developments in association mapping are founded on theory, which has been developed since the beginning of the last century. I hereby review these developments in their...
Genome-wide association mapping under the Malecot model and composite likelihood (2007)
Zhang, W., Jia, W., Hu, C., Maniatis, N., Collins, A., Morton, N.E.
Conference: Abstracts from the Fifteenth Annual Meeting of the International Genetic Epidemiology Society. St. Petersburg, Florida. November 16-17, 2006, St. Petersburg, Florida, 16 November 2006 to...
An investigation of FRAXA intermediate allele phenotype in a longitudinal sample (2006)
Ennis, S., Murray, A., Youings, S., Brightwell, G., Herrick, D., Ring, S., ...
The FRAXA trinucleotide repeat at Xq27.3 gives rise to fragile X syndrome when fully expanded, and both premature ovarian failure (POF) and fragile X tremor and ataxia syndrome (FXTAS) when in the...
Maniatis, N., Gibson, J., Ennis, S., Collins, A., Morton, N.E.
We have developed a simple yet powerful approach for disease gene association mapping by linkage disequilibrium (LD). This method is unique since it applies a model with evolutionary theory that...
Maniatis, N., Morton, N.E., Gibson, J., Hosking, L.K., Collins, A.
We have developed a simple yet powerful approach for disease gene association mapping by linkage disequilibrium (LD). This method is unique because it applies a model with evolutionary theory that...
A map of the human genome in linkage disequilibrium units (2005)
Tapper, W., Collins, A., Gibson, J., Maniatis, N., Ennis, S., Morton, N.E.
Two genetic maps with additive distances contribute information about recombination patterns, recombinogenic sequences, and discovery of genes affecting a particular phenotype. Recombination is...
Positional cloning by linkage disequilibrium (2004)
Maniatis, N., Collins, A., Gibson, J., Zhang, W., Tapper, W., Morton, N.E.
Recently, metric linkage disequilibrium (LD) maps that assign an LD unit (LDU) location for each marker have been developed (Maniatis et al. 2002). Here we present a multiple pairwise method for...
Maniatis, N., Morton, N.E., Gibson, J., Hosking, L.K., Collins, A.
We have developed a simple yet powerful approach for disease gene association mapping by linkage disequilibrium (LD). This method is unique because it applies a model with evolutionary theory that...
Positional cloning by linkage disequilibrium (2004)
Maniatis, N., Collins, A., Gibson, J., Zhang, W., Tapper, W., Morton, N. E.
Recently, metric linkage disequilibrium (LD) maps that assign an LD unit (LDU) location for each marker have been developed (Maniatis et al. 2002). Here we present a multiple pairwise method for...
Does haplotype diversity predict power for association mapping of disease susceptibility? (2004)
Zhang, W., Collins, A., Morton, N. E.
Many recent studies have established that haplotype diversity in a small region may not be greatly diminished when the number of markers is reduced to a smaller set of haplotype-tagging...
A metric linkage disequilibrium map of a human chromosome (2003)
Tapper, W. J., Maniatis, N., Morton, N. E., Collins, A.
We used LDMAP (Maniatis et al. 2002) to analyse SNP data spanning chromosome 22 (Dawson et al. 2002), to obtain a whole-chromosome metric LD map. The LD map, with map distances analogous to the...
Positional cloning by linkage disequilibrium (2003)
Maniatis, N., Collins, A., Gibson, J., Morton, N.E.
Recently, metric linkage disequilibrium (LD) maps that assign an LD unit (LDU) location for each marker have been developed (Maniatis et al. 2002). Here we present a multiple pairwise method for...
Does haplotype diversity predict power for positional cloning? (2003)
Zhang, W., Collins, A., Morton, N.E.
Many recent studies have established that haplotype diversity in a small region may not be greatly diminished when the number of markers is reduced to a smaller set of haplotype-tagging...
Positional cloning by linkage disequilibrium (2003)
Maniatis, N., Collins, A., Gibson, J., Zhang, W., Tapper, W., Morton, N.E.
Recently, metric linkage disequilibrium (LD) maps that assign an LD unit (LDU) location for each marker have been developed (Maniatis et al. 2002). Here we present a multiple pairwise method for...
Properties of linkage disequilibrium (LD) maps (2002)
Zhang, W., Collins, A., Maniatis, N., Tapper, W., Morton, N.E.
A linkage disequilibrium map is expressed in linkage disequilibrium (LD) units (LDU) discriminating blocks of conserved LD that have additive distances and locations monotonic with physical (kb) and...
Maniatis, N., McCarthy, L.C., Hewett, D.R., Tapper, W., ...
Linkage disequilibrium (LD) provides information about positional cloning, linkage, and evolution that cannot be inferred from other evidence, even when a correct sequence and a linkage map based on...
Maniatis, N., Collins, A., Xu, C.F., McCarthy, L.C., Hewett, D.R., Tapper, W., ...
Linkage disequilibrium (LD) provides information about positional cloning, linkage, and evolution that cannot be inferred from other evidence, even when a correct sequence and a linkage map based on...
Recombination, interference and sequence: comparison of chromosomes 21 and 22 (2002)
Tapper, W.J., Ke, X., Morton, N.E., Collins, A.
The euchromatic regions of chromosomes 21 and 22 are almost completely sequenced and have similar lengths (33.7–34.6 Mb). This similarity effectively controls for the influence of length, making...
Toward positional cloning with SNPs (2002)
Efficient methods are available for positional cloning of major genes by linkage and linkage disequilibrium (LD). The application of these methods to complex diseases is more demanding, but advances...
Mapping quantitative effects of oligogenes by allelic association (2002)
Zhang, W., Collins, A., Abecasis, G.R., Cardon, L.R., Morton, N.E.
Regression analysis of a quantitative trait as a function of a single diallelic polymorphism has been extended to allelic association by composite likelihood under the Malecot model for multiple...
Zhang, W., Collins, A., Lonjou, C., Morton, N.E.
Linkage tests to localize oligogenes have been extended during the past year. Using simulated data and multiplex selection we find that several tests on affected sib pairs have comparable power and...
Phylogeny of fragile X haplotypes from an English population (2002)
Ennis, S., Brightwell, G., Collins, A., Jacobs, P., Morton, N.E.
Phylogeny of fragile X haplotypes from an English population (2002)
Ennis, S., Brightwell, G., Collins, A., Jacobs, P., Morton, N.E.
Allelic association with SNPs: metrics, populations, and the linkage disequilibrium map (2001)
Collins, A., Ennis, S., Taillon-Miller, P., Kwok, P-Y., Morton, N. E.
Comparison of different metrics, using three large samples of haplotypes from different populations, demonstrates that rho is the most efficient measure of association between pairs of single...
Allelic association discriminates draft orders (2001)
Ennis, S., Collins, A., Tapper, W., Murray, A., MacPherson, J.N., Morton, N.E.
A year ago there was hope that a finished sequence of the human genome would soon be publicly available and would give a more reliable locus order than an unconstrained radiation hybrid or genetic...
Linkage analysis of the 5q31-33 candidate region for asthma in 240 UK families (2001)
Holloway, J.W., Lonjou, C., Beghe, B., Peng, Q., Gaunt, T.R., Gomes, I., ...
Atopy and asthma are complex genetic diseases resulting from the interactions of a number of genetic and environmental factors. We had previously reported allelic association between the IL9 marker...
Baur, M. P., Majumder, P. P., Amos, C. I., Feingold, J. I., King, T. M., Morton, N. E., ...
The International Genetic Epidemiology Society (IGES) has examined the charges against James V. Neel and his colleagues contained in the recently published book by Patrick Tierney entitled Darkness...
Allelic association with SNPs: metrics, populations, and the linkage disequilibrium map (2001)
Collins, A., Ennis, S., Taillon-Miller, P., Kwok, P-Y., Morton, N. E.
Comparison of different metrics, using three large samples of haplotypes from different populations, demonstrates that is the most efficient measure of association between pairs of single nucleotide...
Complex inheritance: the 21st century (2001)
At least for the early years of the twenty-first century we can anticipate some of the advances to be made in mapping, positional cloning, pooling of evidence over samples for linkage and allelic...
The optimal measure of allelic association (2001)
Morton, N.E., Zhang, W., Taillon-Miller, P., Ennis, S., Kwok, P.Y., Collins, A.
Allelic association between pairs of loci is derived in terms of the association probability ρ as a function of recombination ο, effective population size N, linear systematic pressure v, and time...
Palmer, L.J., Lonjou, C., Barnes, K., Chen, H., Deichmann, K.A., ...
Asthma is the most common chronic childhood disease in developed nations [ 1], affecting more than 155 million individuals. The cost of treating the disease in the USA alone approximates 6 billion...
A tournament of linkage tests in complex inheritance (2001)
Zhang, W., Tapper, W., Collins, A., Jacobs, K. B., Elston, R. C., Morton, N. E.
The performance of some weakly parametric linkage tests in common use was compared on 200 replicates of oligogenic inheritance from Genetic Analysis Workshop 10. Each random sample for the...
Combination of linkage evidence in complex inheritance (2001)
Zhang, W., Collins, A., Morton, N. E.
The central problem of complex inheritance is to combine evidence from data that typically differ in markers, phenotypes, ascertainment, and other factors, without sacrificing the reliability that...
Mapping oligogenes for atopy and asthma by meta-analysis (2000)
Collins,A., Ennis,S., Tapper,W., Morton,N.E.
Meta-analysis is presented for published studies on linkage or allelic association that have in common only reported significance levels. Reporting is biassed, and nonsignificance is seldom...
[Genetic factors involved in asthma and atopy. Studies in British families] (2000)
Thomas, N.S., Wilkinson, J., Lio, P., Doull, I., Morton, N.E., Holgate, S.T.
Both asthma and atopy run families indicating a strong genetic component. To investigate possible candidate gene regions, we have recruited 131 families without reference to atopy and asthma (random...
Allelic association between marker loci
Lonjou, C., Collins, A., Morton, N. E.
Allelic association has proven useful to refine the location of major genes prior to positional cloning, but it is of uncertain value for genome scans in complex inheritance. We have extended kinship...
Teague, J. W., Morton, N. E., Dennis, N. R., Curtis, G., McKechnie, N., Macpherson, J. N., ...
There have been several claims of segregation distortion (meiotic drive) for loci associated with diseases caused by trinucleotide repeats, leading us to test for this phenomenon in a large study of...
Mapping a disease locus by allelic association
Allelic association provides a means to map disease genes that, in a dense map of polymorphic markers, has considerably higher resolution than linkage methods. We describe here a composite likelihood...
Tests and estimates of allelic association in complex inheritance
Family-based procedures such as the transmission disequilibrium test (TDT) were motivated by concern that sample-based methods to map disease genes by allelic association are not robust to population...
Comparison of parametric and nonparametric methods to map oligogenes by linkage
A sample of 95 sib pairs affected with insulin-dependent diabetes and typed with their normal parents for 28 markers on chromosome 6 has been analyzed by several methods. When appropriate parameters...
Genetic epidemiology of single-nucleotide polymorphisms
Collins, A., Lonjou, C., Morton, N. E.
On the causal hypothesis, most genetic determinants of disease are single-nucleotide polymorphisms (SNPs) that are likely to be selected as markers for positional cloning. On the proximity...
Lonjou, C., Barnes, K., Chen, H., Deichmann, K. A., Hall, I. P., ...
The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over...
The optimal measure of allelic association
Morton, N. E., Zhang, W., Taillon-Miller, P., Ennis, S., Collins, A.
Allelic association between pairs of loci is derived in terms of the association probability ρ as a function of recombination θ, effective population size N, linear systematic pressure v, and time...
Studies on locus content mapping.
Teague, J W, Collins, A, Morton, N E
Locus content maps are derived from monosomic or disomic chromosomes broken by radiation, shearing, or other clastogen, the fragments being distributed among clones by dilution or incorporation into...
Trials of the beta model for complex inheritance.
Collins, A, MacLean, C J, Morton, N E
Theoretical advantages of nonparametric logarithm of odds to map polygenic diseases are supported by tests of the beta model that depends on a single logistic parameter and is the only model under...
Logarithm of odds (lods) for linkage in complex inheritance.
Lod scores provide a method to unify linkage tests based on identity by descent and identity in marker state while permitting selection of the most informative individuals through their...
An n-allele model for progressive amplification in the FMR1 locus.
Morris, A, Morton, N E, Collins, A, Macpherson, J, Nelson, D, Sherman, S
An n-allele model is developed for the FMR1 locus, which causes the fragile X syndrome, where n is the number of triplet repeats in the first exon. Frequencies in the general population and in index...
Disomic locus content mapping.
A linear genetic map may be constructed from segregation of markers in DNA fragments broken by radiation or shearing and/or incorporated into a vector: this is locus content mapping. Theory for...
Likelihood ratios for DNA identification.
Likelihood ratio (LR) tests are provided for the three alternatives to DNA identity: exclusion, coincidence, and kinship. The coincidence test uses the radius of coalescence to conserve the observed...
Kinship bioassay on hypervariable loci in blacks and Caucasians.
Morton, N E, Collins, A, Balazs, I
Four hypervariable loci were examined in DNA samples of American Blacks and Caucasians. Genetic diversity, measured by mean kinship within race, is 0.004 for a sliding window equal to twice the...
Integration of gene maps: chromosome 21.
Lawrence, S, Collins, A, Keats, B J, Hulten, M, Morton, N E
Physical, cytogenetic, and genetic data including microsatellite markers and a covering sequence-tagged site (STS) map have been entered into a location database and integrated into a summary map...
Genetic structure of forensic populations.
DNA-based identification depends on the probability that two different individuals have the same phenotype, which is given by kinship theory. Together with the large and consistent body of evidence...
Integration of gene maps: chromosome 1.
Collins, A, Keats, B J, Dracopoli, N, Shields, D C, Morton, N E
A composite map of 177 loci has been constructed in two steps. The first combined pairwise logarithm-of-odds scores on 127 loci into a comprehensive genetic map. Then this map was projected onto the...
Error filtration, interference, and the human linkage map.
Shields, D C, Collins, A, Buetow, K H, Morton, N E
Typing error is a major problem in constructing human linkage maps, leading to incorrect orders and inflating map lengths. An error filter is incorporated into multiple pairwise analysis that...
Parameters of the human genome.
Chromosome arm lengths are the critical parameters of the human genome. The physical length is required to scale radiation hybrid and other maps to megabases. The genetic lengths in males and females...
Lawrence, S, Morton, N E, Cox, D R
A theory is developed to predict marker retention and conditional retention or loss in radiation hybrids. Applied to multiple pairwise analysis of a human chromosome 21 data set, this theory fits...
The first linkage disequilibrium (LD) maps: Delineation of hot and cold blocks by diplotype analysis
Maniatis, N., Collins, A., McCarthy, L. C., Hewett, D. R., Tapper, W., ...
Linkage disequilibrium (LD) provides information about positional cloning, linkage, and evolution that cannot be inferred from other evidence, even when a correct sequence and a linkage map based on...
Effect of inbreeding on IQ and mental retardation.
Both decline of IQ and increase of mental retardation are consistent with rare recessive alleles at about 325 loci. There is no suggestion of a discrepancy that might be due to polygenic dominance or...
Population genetics of the fragile-X syndrome: multiallelic model for the FMR1 locus.
A model is developed to account for recent molecular observations. It postulates four alleles: normal (N), small rather stable insert (S), larger, unstable insert (Z), and large insert (L). The...
A map of the human genome in linkage disequilibrium units
Tapper, W., Collins, A., Gibson, J., Maniatis, N., Ennis, S., Morton, N. E.
Two genetic maps with additive distances contribute information about recombination patterns, recombinogenic sequences, and discovery of genes affecting a particular phenotype. Recombination is...
Significance levels in complex inheritance.
A LOD score >=3 is necessary but not sufficient to make a linkage test reliable, and this applies to complex inheritance as well as to major loci. Factors that affect this threshold are considered...
Genetic Effects of Cumulative Irradiation on Prenatal and Early Postnatal Survival in the Rat
Chapman, A. B., Hansen, Janet L., Havenstein, G. B., Morton, N. E.
Genetic Effects of Cumulative X Irradiation on the Secondary Sex Ratio of the Laboratory Rat
Havenstein, G. B., Taylor, B. A., Hansen, Janet C., Morton, N. E., Chapman, A. B.
The use of map functions in multipoint mapping.
The analysis of multipoint data in humans involves detection of linkage, inferences about order, and estimation of map lengths. In order to calculate likelihoods, it i