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Biomedical subjects

N E Morton

Publications and source records attributed to N E Morton.

At least 19 recordsLinked to original sources
PubMed1992

Oculoauriculovertebral anomaly: segregation analysis.

Seventy-four families of probands with oculoauriculovertebral anomaly were evaluated, including 116 parents and 195 offspring. Relatives were examined to identify ear malformations, mandibular anomalies, and other craniofacial abnormalities. For segregation analysis using POINTER, selection of the sample was consistent with single ascertainment. Different population liabilities were used for probands and relatives, because affection was narrowly defined for probands and broadly defined for relatives. The hypothesis of no genetic transmission was rejected. The evidence favored autosomal dominant inheritance; recessive and polygenic models were not distinguishable.

Adult↗
PubMed1992

Integration of gene maps: chromosome 1.

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 physical map through cytogenetic assignments, and the small amount of physical data was interpolated for an additional 50 loci each of which had been assigned to an interval of less than 10 megabases. The resulting composite map is on the physical scale with a resolution of 1.5 megabases. In the future these methods may be used to incorporate locations from linkage, contigs, radiation hybrids, restriction fragments, and somatic cell maps. Dense, reliable, and well-documented maps are essential for long-range sequencing and to localize and clone disease genes.

Animals↗
PubMed1992

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 last-named allele causes the fragile-X phenotype, inactivation of the FMR1 locus by methylation, and mental impairment; the FMR1 locus (for fragile-X mental retardation locus 1) resides in the FRAXA region. When this model is fit to pre-molecular data, the Z allele appears to be no more frequent than L, while the S allele is polymorphic. Predictions of the model are in reasonable agreement with observation and suggest much more powerful tests of molecular data, including the Laird hypothesis that conversion of Z to L does not occur in active X chromosomes.

Alleles↗
PubMed1992

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 on human population structure, kinship theory provides a sound basis for forensic use of DNA markers.

DNA Fingerprinting↗
PubMed1992

Dominant genes for colorectal cancer are not rare.

The genetic basis for colorectal cancer was investigated by complex segregation analysis of a published series of consecutive pedigrees ascertained through patients undergoing treatment for colorectal cancer. Analysis favoured a dominant gene or genes with a frequency of 0.006 with a lifetime penetrance of 0.63. These genes account for 81% of colorectal cancer in patients under 35, however, by 65 about 85% are phenocopies.

Adult↗
PubMed1992

Algorithms for a location database.

The algorithms that drive the ldb location database are described. The program captures data on genetic and physical maps and combines information from different sources into a summary map. To assure portability it was developed in Fortran on a SUN SPARCStation under Unix. The algorithms, which combine rule-based seriation with a minimum deviance bootstrap, allow investigators and chromosome committees to produce a composite location in Mb that integrates partial maps. The program and manual are now available from the authors.

Algorithms↗
PubMed1992

The AD1 locus in familial Alzheimer disease.

The AD1 locus on chromosome 21 (MIM 104300) maps to the beta-amyloid precursor locus (APP) at approximately 27.7 Mb from pter (10.9 cM in males and 33.9 cM in females), flanked proximally by D21S8 and distally by D21S111, with D21S124 and D21S210 close but of uncertain order. AD1 accounts for 63 +/- 11% of multiplex Alzheimer pedigrees for which lod scores have been reported. Since a much smaller proportion of pedigrees have mutations in the cDNA for beta-amyloid (APP exons 16 and 17), it is likely that the AD1 locus spans controlling elements near those exons. There is no evidence for a second locus on chromosome 21. The remaining pedigrees may include sporadic cases as well as mutations at an AD2 locus on another chromosome.

Alzheimer Disease↗
PubMed1992

The future of genetic epidemiology.

Starting from a broad definition of genetic epidemiology, current developments in association, segregation, and linkage analysis of complex inheritance are considered together with integration of genetic and physical maps and resolution of genetic heterogeneity. Mitochondrial inheritance, imprinting, uniparental disomy, pregressive amplification, and gonadal mosaicism are some of the novel mechanisms discussed, with speculation about the future of genetic epidemiology.

Computers↗
PubMed1991

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 are required for probabilities of exclusion and synteny, choice of well-spaced loci for linkage tests, and comparison with centromeric maps based on nondisjunction. Interpolation of new data into a map is possible only when the length is known, including the distances from centromere and telomeres to the nearest markers. Current evidence on physical parameters including the reliable measurements of relative lengths from flow cytometry but only a crude estimate of genome size (3200 megabases). Evidence on genetic parameters includes chiasma counts and linkage maps corrected for failure to sample telomeres, giving an autosomal size of 2809 centimorgans in males and 4782 centimorgans in females. Estimates of the physical and sex-specific genetic lengths are presented for each chromosome arm. Any linkage analysis that yields substantially larger estimates raises a suspicion of an inappropriate mapping function or typing errors.

Chromosome Mapping↗
PubMed1991

Radiation hybrid mapping.

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 much better than proposed alternatives and gives a physical map consistent with other evidence and robust with respect to errors to typing. Radiation hybrids have great promise to provide order and physical location at two levels of resolution, spanning the techniques of linkage and restriction fragments and not limited to polymorphic loci.

Centromere↗
PubMed1991

Error filtration, interference, and the human linkage map.

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 corrects for inflation of map lengths and improves recovery of the correct order. Multipoint mapping is more sensitive to error, but when its output is adjusted for both error and interference, map lengths are no longer inflated in proportion to the number of loci and are close to those obtained by multiple pairwise analysis.

Algorithms↗
PubMed1991

Genetic epidemiology of breast cancer in Britain.

A complex segregation analysis was conducted on two British series (one consecutive series of probands with breast cancer and one series ascertained through a normal consultand). Altogether there were 1248 nuclear families with breast cancer. A dominant gene with a frequency of 0.003 giving a lifetime penetrance of 0.83 is favoured. Ovarian, endometrial and cancers associated with the SBLA syndrome, as well as benign breast disease, were significantly more common in familial breast cancer than in families of single cases. Probands in families with more than one individual with breast cancer were non-significantly younger than isolated probands.

Adult↗
PubMed1991

Gene maps and location databases.

A location database is defined in linear space by a vector of genetic and physical locations for each locus, which may be ordered by virtual sorting on composite location. This contrasts with an interval database defined in metric space, for which location must be inferred by list-processing from numbered intervals which are assigned different ordinals in different tables and overlap other intervals in many ways. A location database has been used for all well-studied experimental organisms. Principles for a human genome database may be derived from this experience.

Animals↗